phases
list | enrollmentCount
int64 | allocation
string | interventionModel
string | primaryPurpose
class label | masking
class label | healthyVolunteers
bool | sex
class label | oversightHasDmc
bool | briefSummary
string | detailedDescription
string | conditions
string | conditionsKeywords
string | protocolPdfText
string | numArms
int64 | armDescriptions
string | armGroupTypes
list | numInterventions
int64 | interventionTypes
list | interventionDescriptions
string | interventionNames
string | numLocations
int64 | locationDetails
string | target
int64 | nctid
string |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[
3
] | 104
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it is no longer present by conventional imaging and tumor markers from serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill more tumor cells.
PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without surgery and with or without high dose chemotherapy and peripheral stem cell transplantation, can increase response rates prior to radiation therapy and increase progression free and overall surviving patients with newly diagnosed intracranial germ cell tumors.
|
OBJECTIVES:
* Determine the response rate of patients with non-germinomatous germ cell tumors treated with neoadjuvant chemotherapy.
* Determine the progression-free survival and overall survival of patients treated with neoadjuvant chemotherapy with or without second-look surgery followed by radiotherapy with or without autologous peripheral blood stem cell transplantation (PBSCT).
* Determine whether additional complete responses can be achieved after high-dose thiotepa and etoposide with PBSCT in patients with persistently positive markers, histological evidence of residual malignant elements, or unresectable residual tumors after initial neoadjuvant chemotherapy.
* Determine patterns of recurrence in patients treated with this regimen.
* Correlate tumor marker response with radiographic and clinical measures of response, as well as findings at second-look surgery in patients with radiological evidence of residual disease.
OUTLINE:
* Induction chemotherapy:
* Courses 1, 3, and 5: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3. Beginning on day 4, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) for 10 days or until blood counts recover. Courses are 3 weeks in duration.
* Courses 2, 4, and 6: Patients receive etoposide IV over 1 hour followed by ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive G-CSF IV or SC for 10 days or until blood counts recover. Courses are 3 weeks in duration.
Patients undergo re-evaluation. Patients with a complete response (CR) go directly to radiotherapy. Approximately 3 weeks after completion of induction chemotherapy, all patients with less than a CR are encouraged to undergo second-look surgery.
After second-look surgery, patients with a CR or a partial response (PR) go directly to radiotherapy. Patients with less than a PR undergo consolidation chemotherapy with peripheral blood stem cell rescue (PBSC) followed by radiotherapy.
* Consolidation chemotherapy: Patients undergo PBSC collection. Patients receive G-CSF SC until PBSC collection is complete. Patients then receive thiotepa IV over 3 hours followed by etoposide IV over 3 hours on days -5 to -3. PBSCs are reinfused on day 0. Beginning on day 1 and continuing until blood counts recover, patients receive G-CSF SC daily.
* Radiotherapy: All patients receive radiotherapy once daily 5 days a week for 5-6 weeks beginning after recovery from induction chemotherapy or second-look surgery or within 9 weeks after PBSC reinfusion.
Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 80-100 patients will be accrued for this study within 36-42 months.
|
Brain Tumor Central Nervous System Tumors Childhood Germ Cell Tumor
|
childhood central nervous system germ cell tumor childhood teratoma recurrent childhood malignant germ cell tumor childhood central nervous system choriocarcinoma childhood central nervous system embryonal tumor childhood central nervous system germinoma childhood central nervous system mixed germ cell tumor childhood central nervous system teratoma childhood central nervous system yolk sac tumor recurrent childhood central nervous system embryonal tumor
| null | 1
|
arm 1: Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
|
[
0
] | 9
|
[
0,
0,
0,
0,
3,
3,
3,
3,
4
] |
intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: None intervention 6: None intervention 7: None intervention 8: None intervention 9: craniospinal irradiation
|
intervention 1: carboplatin intervention 2: etoposide intervention 3: ifosfamide intervention 4: thiotepa intervention 5: adjuvant therapy intervention 6: conventional surgery intervention 7: neoadjuvant therapy intervention 8: peripheral blood stem cell transplantation intervention 9: radiation therapy
| 106
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Phoenix | Arizona | United States | -112.07404 | 33.44838
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Downey | California | United States | -118.13257 | 33.94001
Loma Linda | California | United States | -117.26115 | 34.04835
Long Beach | California | United States | -118.18923 | 33.76696
Los Angeles | California | United States | -118.24368 | 34.05223
Madera | California | United States | -120.06072 | 36.96134
Oakland | California | United States | -122.2708 | 37.80437
Orange | California | United States | -117.85311 | 33.78779
Sacramento | California | United States | -121.4944 | 38.58157
San Diego | California | United States | -117.16472 | 32.71571
San Francisco | California | United States | -122.41942 | 37.77493
Stanford | California | United States | -122.16608 | 37.42411
Farmington | Connecticut | United States | -72.83204 | 41.71982
Wilmington | Delaware | United States | -75.54659 | 39.74595
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Fort Myers | Florida | United States | -81.84059 | 26.62168
Gainesville | Florida | United States | -82.32483 | 29.65163
Jacksonville | Florida | United States | -81.65565 | 30.33218
Miami | Florida | United States | -80.19366 | 25.77427
Miami | Florida | United States | -80.19366 | 25.77427
Orlando | Florida | United States | -81.37924 | 28.53834
Pensacola | Florida | United States | -87.21691 | 30.42131
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Tampa | Florida | United States | -82.45843 | 27.94752
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Atlanta | Georgia | United States | -84.38798 | 33.749
Augusta | Georgia | United States | -81.97484 | 33.47097
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Park Ridge | Illinois | United States | -87.84062 | 42.01114
Springfield | Illinois | United States | -89.64371 | 39.80172
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Kansas City | Kansas | United States | -94.62746 | 39.11417
Baltimore | Maryland | United States | -76.61219 | 39.29038
Boston | Massachusetts | United States | -71.05977 | 42.35843
Boston | Massachusetts | United States | -71.05977 | 42.35843
Detroit | Michigan | United States | -83.04575 | 42.33143
Grand Rapids | Michigan | United States | -85.66809 | 42.96336
Grosse Pointe Woods | Michigan | United States | -82.90686 | 42.44365
Lansing | Michigan | United States | -84.55553 | 42.73253
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Rochester | Minnesota | United States | -92.4699 | 44.02163
Jackson | Mississippi | United States | -90.18481 | 32.29876
Kansas City | Missouri | United States | -94.57857 | 39.09973
St Louis | Missouri | United States | -90.19789 | 38.62727
Hackensack | New Jersey | United States | -74.04347 | 40.88593
New Brunswick | New Jersey | United States | -74.45182 | 40.48622
Newark | New Jersey | United States | -74.17237 | 40.73566
Paterson | New Jersey | United States | -74.17181 | 40.91677
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Syracuse | New York | United States | -76.14742 | 43.04812
The Bronx | New York | United States | -73.86641 | 40.84985
Valhalla | New York | United States | -73.77513 | 41.07482
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Durham | North Carolina | United States | -78.89862 | 35.99403
Akron | Ohio | United States | -81.51901 | 41.08144
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cleveland | Ohio | United States | -81.69541 | 41.4995
Columbus | Ohio | United States | -82.99879 | 39.96118
Dayton | Ohio | United States | -84.19161 | 39.75895
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Portland | Oregon | United States | -122.67621 | 45.52345
Hershey | Pennsylvania | United States | -76.65025 | 40.28592
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Providence | Rhode Island | United States | -71.41283 | 41.82399
Charleston | South Carolina | United States | -79.93275 | 32.77632
Sioux Falls | South Dakota | United States | -96.70033 | 43.54997
Memphis | Tennessee | United States | -90.04898 | 35.14953
Nashville | Tennessee | United States | -86.78444 | 36.16589
Austin | Texas | United States | -97.74306 | 30.26715
Corpus Christi | Texas | United States | -97.39638 | 27.80058
Dallas | Texas | United States | -96.80667 | 32.78306
Fort Worth | Texas | United States | -97.32085 | 32.72541
Lubbock | Texas | United States | -101.85517 | 33.57786
San Antonio | Texas | United States | -98.49363 | 29.42412
San Antonio | Texas | United States | -98.49363 | 29.42412
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Norfolk | Virginia | United States | -76.28522 | 36.84681
Charleston | West Virginia | United States | -81.63262 | 38.34982
Green Bay | Wisconsin | United States | -88.01983 | 44.51916
Marshfield | Wisconsin | United States | -90.1718 | 44.66885
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Brisbane | Queensland | Australia | 153.02809 | -27.46794
Parkville | Victoria | Australia | 144.95 | -37.78333
Perth | Western Australia | Australia | 115.8614 | -31.95224
Vancouver | British Columbia | Canada | -123.11934 | 49.24966
St. John's | Newfoundland and Labrador | Canada | -52.70931 | 47.56494
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Toronto | Ontario | Canada | -79.39864 | 43.70643
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Saskatoon | Saskatchewan | Canada | -106.66892 | 52.13238
Québec | N/A | Canada | -71.21454 | 46.81228
Auckland | N/A | New Zealand | 174.76349 | -36.84853
Christchurch | N/A | New Zealand | 172.63333 | -43.53333
Bern | N/A | Switzerland | 7.44744 | 46.94809
Geneva | N/A | Switzerland | 6.14569 | 46.20222
| 0
|
NCT00047320
|
[
3
] | 18
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging.
In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH.
...
|
Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging.
In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH.
|
Hepatitis
|
Insulin Resistance Obesity Fatty Liver Cirrhosis Diabetes Pioglitazone Thiazolidinediones Peroxisome Proliferator-Advanced Receptor Gamma PPAR Gama Nonalcoholic Steatohepatitis Hepatitis Non-Alcoholic Steatohepatitis NASH
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: Pts receive drug in a dose of 15 mg daily for at least 1 year; the dose is escalated to 30 mg daily if serum ALT levels do not fall to normal by the 1 year pt; if pts have a biochemical response, drug is continued for 3 years,
|
intervention 1: Actos (Pioglitazone)
| 1
|
Bethesda | Maryland | United States | -77.10026 | 38.98067
| 0
|
NCT00062764
|
[
3
] | 26
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as temozolomide may make the tumor cells more sensitive to radiation therapy. Combining temozolomide with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving temozolomide together with whole-brain radiation therapy works in treating patients with brain metastasis secondary to non-small cell lung cancer.
|
OBJECTIVES:
Primary
* Determine the intracranial response rate in patients with brain metastasis secondary to non-small cell lung cancer treated with whole brain radiotherapy and temozolomide.
Secondary
* Determine the time to radiological progression in patients treated with this regimen.
* Determine the time to neurological progression (confirmed by magnetic resonance imaging (MRI)) in patients treated with this regimen.
* Determine the overall survival of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients undergo whole brain radiotherapy once daily, 5 days a week, for 2 weeks (10 fractions). Patients also receive concurrent oral temozolomide once daily on days 1-14.
Beginning 3 weeks after the completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of neurologic (Central Nervous System, CNS) progression or unacceptable toxicity.
Patients were followed every 3 months for 2 years.
ACCRUAL: A total of 26 patients were accrued for this study.
|
Lung Cancer Metastatic Cancer
|
recurrent non-small cell lung cancer stage IV non-small cell lung cancer squamous cell lung cancer adenocarcinoma of the lung large cell lung cancer bronchoalveolar cell lung cancer adenosquamous cell lung cancer tumors metastatic to brain
| null | 1
|
arm 1: Temozolomide:administered orally. Radiation: whole brain radiation therapy
|
[
0
] | 2
|
[
0,
4
] |
intervention 1: Temozolomide (TMZ) to be given at a dose of 75 mg/m2/day for 14 days, starting on D1 of whole brain radiotherapy (WBRT). Three weeks after completion of WBRT, TMZ will be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28-days,for an additional two cycles. intervention 2: Standard whole brain radiation therapy 30 Gy in ten fractions.
|
intervention 1: Temozolomide intervention 2: Radiation therapy
| 0
| null | 0
|
NCT00080938
|
[
3
] | 41
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The goal of this clinical research study is to learn if CC-5013 (lenalidomide) can help to control myelofibrosis. The safety of lenalidomide in the treatment of myelofibrosis will also be studied.
|
Lenalidomide blocks the activity of a substance in the blood called tumor necrosis factor alpha. Tumor necrosis factor alpha is a substance that is believed to prevent new blood cells from forming in the bone marrow. Lenalidomide is also believed to help the body's immune system fight diseases.
Before treatment starts, you will have a complete physical exam, including blood (about 3 teaspoonfuls) and urine tests. A bone marrow sample will be taken. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. An ECG (test to measure the electrical activity of the heart) may be performed.
Women who are able to have children must have a negative pregnancy test \[blood (about 1 teaspoon) or urine\]. These pregnancy tests must occur within 10 - 14 days and again within 24 hours before the start of lenalidomide. Women who are able to have children with regular or no menstruation must have a pregnancy test weekly for the first 28 days and then every 28 days while on therapy (including breaks in therapy); when they stop taking lenalidomide and at Day 28 after the last dose of lenalidomide. Females with irregular menstruation must have a pregnancy test weekly for the first 28 days and then every 14 days while on therapy (including breaks in therapy), when they stop taking lenalidomide and at Day 14 and Day 28 after the last dose of lenalidomide.
You are considered to be a woman who is able to have children if you are a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
You will take 2 lenalidomide capsules by mouth daily. You should swallow lenalidomide capsules whole with water at the same time each day. Do not break, chew or open the capsules. If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).
If your platelet count is less than 100,000 at the time of study enrollment, the dose will be one capsule daily. The dose may be decreased depending on side effects. The dose may be increased if needed to better control the disease. This will be decided cycle by cycle.
During treatment, you will give blood samples (about 1 tablespoon each) about every week. The tests may be repeated more frequently to check for side effects. You will need to return to M. D. Anderson monthly for the first 3 months, then at least every 3 months afterwards (while on the study) in order to be evaluated for response and tolerance to lenalidomide. Only one 28-day cycle of lenalidomide may be given to you for each cycle per month.
You may continue to receive this therapy as long as there are no severe side effects or worsening of the disease. You will be asked to keep diaries documenting when you take the capsules. You will also need to return empty medication bottles at each visit. If you have had 4 to 6 months of treatment without any evidence of benefit, you may be taken off the study.
This is an investigational study. Lenalidomide is a new drug related to the drug called thalidomide. Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM are cancers of the blood. It is currently being tested in a variety of cancer conditions. In this case it is considered investigational. Up to 41 participants may take part in this study. All will be enrolled at M. D. Anderson.
|
Myelofibrosis
|
Myelofibrosis Philadelphia negative myeloproliferative disorder CC-5013 Lenalidomide Revlimid Antiangiogenesis
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: 10 mg orally (2 capsules) daily
|
intervention 1: CC-5013
| 1
|
Houston | Texas | United States | -95.36327 | 29.76328
| 0
|
NCT00087672
|
[
3
] | 73
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| true
|
This study will determine the effectiveness of adding S-adenosyl methionine to antidepressant drug treatment in reducing depressive symptoms in depressed people who have not responded to antidepressants alone.
|
Some people with depression do not respond well to antidepressant treatment. S-adenosyl methionine (SAMe) is a naturally occurring compound that may have antidepressant effects. SAMe may also enhance the effectiveness of other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). This study will determine the effectiveness of oral SAMe in enhancing the effects of SSRIs in patients currently not responding to SSRI treatment.
This study will last 6 weeks. No follow-up visits will occur. Participants will be randomly assigned to add either oral SAMe or placebo to their existing SSRI regimen for 6 weeks. Depression scales and self-report questionnaires regarding depressive symptoms will be used to assess participants at the end of the study.
|
Depression
|
Selective Serotonin Reuptake Inhibitors S-adenosyl Methionine SSRI SAMe
| null | 2
|
arm 1: Participants receiving the oral SAMe tosylate arm 2: Participants receiving placebo
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Oral SAMe tosylate, up to 1600 mg per day for 6 weeks intervention 2: Placebo to be taken daily for 6 weeks
|
intervention 1: S-adenosyl methione (SAMe) intervention 2: Placebo
| 1
|
Boston | Massachusetts | United States | -71.05977 | 42.35843
| 0
|
NCT00093847
|
[
0
] | 25
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 1FEMALE
| true
|
Androgen deficiency in HIV-infected women is associated with sarcopenia and may cause critical reductions in physical functioning and reduced bone density. The effects of long-term androgen therapy on lean body mass, bone density and other clinical endpoints including quality of life, functional status and neurocognitive function in HIV-infected women are not known.
|
We will perform an 18-month randomized, double-blinded, placebo-controlled study among relatively androgen deficient women with HIV, to determine the effects of testosterone administration on lean body mass. The administered dose will be 300 micrograms twice a week vs. identical placebo in the form of a transdermal preparation. Secondary endpoints include effects on bone density, quality of life, neurocognitive function and menstrual function. Open label administration at 300 micrograms twice a week will be initiated for 12 months in all subjects following the randomized portion of the study. Assuming a 15% dropout rate and 25 randomized patients, the probability is 80 percent that the study will detect a treatment difference at a two sided 5.000 percent significance level, if the true difference between the treatments is 2.7 kg. This is based on the assumption that the standard deviation of the response variable, lean body mass by DEXA, is 2.3 kg, as was shown by Choi et al1 over 12 weeks in HIV-infected women at the same dose of 300 ug 2x/week.
|
HIV Infection
|
HIV women androgen Treatment Experienced
| null | 2
|
arm 1: 300 micrograms applied twice a week arm 2: placebo patch (0 micrograms of testosterone)applied twice a week
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: 300 micrograms twice a week intervention 2: Placebo patch (0 micrograms of testosterone) applied twice a week
|
intervention 1: 1 Transdermal Testosterone (Patch) intervention 2: 2 Placebo Patch
| 1
|
Boston | Massachusetts | United States | -71.05977 | 42.35843
| 0
|
NCT00095212
|
[
4
] | 682
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The SCORE Study will compare the effectiveness and safety of standard care to intravitreal injection(s) of triamcinolone for treating macular edema (swelling of the central part of the retina) associated with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO).
|
Macular edema is a major cause of vision loss in patients with CRVO and BRVO. Both CRVO and BRVO are common retinal problems and are caused by a blockage in one of the large retinal veins (central retinal vein occlusion - CRVO) or smaller retinal veins (branch retinal vein occlusion - BRVO). Currently, there is no effective treatment for macular edema associated with CRVO and standard care treatment is observation. Grid laser photocoagulation may be effective for some patients for macular edema associated with BRVO, but many patients derive limited benefit from this treatment. Therefore, the development of new treatment modalities for macular edema caused by these two conditions is an important research goal.
Over the last several years, many patients with macular edema from CRVO and BRVO have been treated with an injection of a type of steroid called triamcinolone directly into the eye. This type of injection is called an intravitreal injection. The triamcinolone preparation commonly injected into the eye is Kenalog and is FDA-approved only for use in muscles and joints. The SCORE Study will use a formulation of triamcinolone made specifically for the eye.
The SCORE Study is a multicenter, randomized, Phase III trial to compare the effectiveness and safety of standard care versus triamcinolone injection(s) for the treatment of macular edema associated with CRVO and BRVO. In each of the two disease areas, 630 participants will be randomized (similar to a flip of a coin) in a 1:1:1 ratio to one of three groups: standard care, intravitreal triamcinolone 4 mg, or intravitreal triamcinolone 1 mg. After randomization, participants will be examined every 4 months through 3 years to collect ophthalmic information, including visual acuity, intraocular pressure, optical coherence tomography, and fundus photography . Fluorescein angiography will be performed at 4, 12 and 24 months. Repeat intravitreal injections of triamcinolone and repeat laser treatment will be provided as clinically indicated based on protocol-specific guidelines.
The primary outcome is improvement by 15 or more letters from baseline in best-corrected ETDRS visual acuity score at the 12-month visit. Secondary outcomes include changes from baseline in best-corrected ETDRS visual acuity score, changes in retinal thickness as assessed by stereoscopic color fundus photography and optical coherence tomography, and adverse ocular outcomes.
|
Macular Edema, Cystoid Retinal Vein Occlusion
|
macular edema central retinal vein occlusion (CRVO) branch retinal vein occlusion (BRVO)
|
Prot_SAP_000.pdf:
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
The Standard Care vs. COrticosteroid for
REtinal Vein Occlusion (SCORE) Study
Two Randomized Trials to Compare the Efficacy and Safety of Intravitreal Injection(s)
of Triamcinolone Acetonide with Standard Care to Treat Macular Edema: One for
Central Retinal Vein Occlusion and One for Branch Retinal Vein Occlusion
Version 7.0 — February 10, 2008
Study Chair
Study Co-Chair
Michael S. Ip, MD
Ingrid U. Scott, MD, MPH
University of Wisconsin Medical School
Professor of Ophthalmology and
Dept of Ophthalmology and Visual Sciences
Health Evaluation Sciences
F4/336 Clinical Science Center
Penn State College of Medicine
600 Highland Avenue
500 University Drive, HU19
Madison, WI 53792
Hershey, PA 17033
Tel: 608-263-4823
Tel: 717-531-5368
Fax: 608-263-1466
Fax: 717-531-5475
E-mail: msip@facstaff.wisc.edu
E-mail: iscott@psu.edu
Principal Investigator
Principal Investigator
Data Coordinating Center
Fundus Photograph Reading Center
Paul C. VanVeldhuisen, PhD
Barbara A. Blodi, MD
The EMMES Corporation
406 Science Drive, Suite 400
401 N. Washington Street, Suite 700
Madison, WI 53711
Rockville, MD 20850-1785
Tel: 608-263-7290
Tel: 301-251-1161 x143
Fax: 608-263-1466
Fax: 800-546-9262
E-mail: bablodi@facstaff.wisc.edu
E-mail: pvanveldhuisen@emmes.com
NEI Program Officer
DSMC Chair
Maryann Redford, DDS, MPH
John Connett, PhD
National Eye Institute
University of Minnesota
6120 Executive Blvd., Suite 350
Coordinating Centers for Biometric Research
Bethesda, MD 20892
2221 University Avenue SE, Room 200
Tel: 301-451-2020
Minneapolis, MN 55414
Fax: 301-402-0528
Tel: 612-626-9010
E-mail: maryann.redford@nei.nih.gov
Fax: 612-626-9054
E-mail: john-c@blueox.ccbr.umn.edu
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
i
Table of Contents
PRÉCIS
.................................................................................................................................... 1
1.
INTRODUCTION................................................................................................................ 3
2.
BACKGROUND AND SCIENTIFIC JUSTIFICATION ................................................ 3
2.1 Venous Occlusive Disease .................................................................................................... 3
2.2 Pathogenesis of Macular Edema ......................................................................................... 6
2.3 Animal and Clinical Studies Using Intravitreal Triamcinolone Acetonide Injections .. 8
2.4 Other Studies Evaluating Corticosteroid Preparations Other Than Triamcinolone
Acetonide for Treatment of Macular Edema due to Retinal Vascular Disease ........... 16
2.4.1
Efficacy ..................................................................................................................... 16
2.4.2
Adverse Effects ......................................................................................................... 17
2.5 Rationale for the Intravitreal Triamcinolone Acetonide Doses to be Evaluated ......... 18
2.6 Mechanism of Adverse Effects Associated with Intravitreal Steroids .......................... 20
2.6.1
Elevation of Intraocular Pressure .............................................................................. 20
2.6.2
Cataract Formation .................................................................................................... 21
2.6.3
Endophthalmitis ........................................................................................................ 22
3.
OBJECTIVES .................................................................................................................... 24
4.
STUDY DESIGN AND METHODS................................................................................. 24
4.1 Efficacy Assessment ........................................................................................................... 25
4.1.1
Primary Efficacy Outcome ........................................................................................ 25
4.1.2
Secondary Efficacy Outcomes .................................................................................. 25
4.2 Safety Assessments ............................................................................................................. 26
4.2.1
Safety Outcomes ....................................................................................................... 26
4.3 Inclusion Criteria ............................................................................................................... 26
4.3.1
General Inclusion Criteria ......................................................................................... 26
4.3.2
Ocular Inclusion Criteria (study eye) ........................................................................ 26
4.4 Exclusion Criteria .............................................................................................................. 28
4.4.1
General Exclusion Criteria ........................................................................................ 28
4.4.2
Ocular Exclusion Criteria (study eye) ....................................................................... 29
4.4.3
Fellow (Non-Study) Eye Criteria (the Fellow Eye Must Meet the Following) ......... 31
4.5 Informed Consent, Screening Evaluation, and Randomization .................................... 32
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
ii
4.5.1
Informed Consent ...................................................................................................... 32
4.5.2
Screening Evaluation ................................................................................................ 32
4.5.3
Randomization .......................................................................................................... 34
4.6 Standard Care Groups ...................................................................................................... 35
4.6.1
Photocoagulation Procedures .................................................................................... 35
4.7 Intravitreal Steroid Groups .............................................................................................. 36
4.7.1
Intravitreal Injection of Triamcinolone Acetonide.................................................... 36
4.8 Participant Visit Schedule, Retreatment, Alternate Treatment and Other Treatments37
4.8.1
Visit Schedule ........................................................................................................... 37
4.8.2
Testing Procedures to be Performed at Follow-up Visits (see Appendix 1) ............. 38
4.8.3
Retreatment Assessment ........................................................................................... 39
4.8.4
Alternate Treatment for the Study Eye ..................................................................... 42
4.8.5
Other Treatments ...................................................................................................... 43
4.9 Diagnosis and Treatment of Adverse Events ................................................................... 43
4.9.1
Endophthalmitis Treatment ....................................................................................... 43
4.9.2
Treatment of Elevated Intraocular Pressure (IOP) .................................................... 43
4.9.3
Cataract Surgery ........................................................................................................ 44
4.9.4
Surgery for Proliferative Retinopathy and Other Complications Due to Retinal Vein
Occlusion ................................................................................................................. 45
4.10 Miscellaneous Treatments During Follow-up ................................................................. 46
4.10.1
Treatment of Macular Edema in Non-study Eye ...................................................... 46
4.10.2
Panretinal Photocoagulation (PRP) Treatment: ........................................................ 46
5.
DATA MONITORING AND ADVERSE EVENT REPORTING ................................ 47
5.1 Data Safety Monitoring Committee ................................................................................. 47
5.2 Methods and Timing for Assessing, Recording and Analyzing Safety Parameters .... 48
5.3 Procedures for Reporting Adverse Events ...................................................................... 49
5.3.1
Routine SCORE DCC Review ................................................................................. 49
5.3.2
Adverse Event Severity Grading ............................................................................... 51
5.3.3
Relation to Therapy ................................................................................................... 52
5.3.4
Adverse Event Reporting Requirements and Procedures for Clinical Sites to the
SCORE Coordinating Center ................................................................................... 52
5.3.5
Reporting Procedures ................................................................................................ 53
5.3.6
SCORE Adverse Event Reporting Contact ............................................................... 53
5.4 Procedure for Reporting of Pregnancy ............................................................................ 54
6.
STATISTICAL CONSIDERATIONS ............................................................................. 54
6.1 Scientific and Regulatory Objectives ............................................................................... 54
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
iii
6.2 Formal Regulatory Statistical Test of Efficacy ............................................................... 55
6.3 Scientific Statistical Approach .......................................................................................... 56
6.3.1
Two Independent Clinical Trials ............................................................................... 56
6.3.2
Three Primary Questions in Each Clinical Trial ....................................................... 56
6.4 Assumptions for and Result of Sample Size Estimation................................................. 58
6.4.1
Study Power .............................................................................................................. 58
6.4.2
Estimate of CRVO Primary Efficacy Outcome in the Standard Care Group ........... 58
6.4.3
Estimate of BRVO Primary Efficacy Outcome in the Standard Care Group ........... 58
6.4.4
Background Information on Efficacy of Intravitreal Injection(s) of Triamcinolone
Acetonide ................................................................................................................. 59
6.4.5
Sample Size Estimate ................................................................................................ 60
6.5 Safety Outcomes ................................................................................................................. 61
6.6 Secondary Efficacy Outcomes .......................................................................................... 62
6.7 Statistical Guidelines for Interim Monitoring by the DSMC ........................................ 63
6.7.1
Interim Monitoring for Safety ................................................................................... 63
6.7.2
Interim Monitoring for Efficacy ................................................................................ 63
6.7.3
Interim Monitoring for Futility ................................................................................. 64
6.7.4
Analyses and Results Requested to be Considered Prior to Recommending Early
Termination .............................................................................................................. 64
6.7.5
Study Timeline and DSMC Data Reviews ............................................................... 65
7.
CONFIDENTIALITY AND ACCESS TO SOURCE DATA / DOCUMENTS ........... 66
8.
SUMMARY OF GOOD CLINICAL PRACTICE COMPLIANCE ............................. 66
8.1 Investigator Responsibilities (Form FDA-1572) .............................................................. 66
8.2 Human Subjects Protection............................................................................................... 67
8.2.1
Institutional Review Board or Independent Ethics Committee ................................. 67
8.3 Data Handling and Recordkeeping .................................................................................. 68
8.3.1
Case Report Forms .................................................................................................... 68
8.3.2
Data Transmittal ........................................................................................................ 68
8.4 Professional Licensure ....................................................................................................... 69
8.5 Human Subjects Protection Training .............................................................................. 69
9.
REFERENCES ................................................................................................................... 70
10. APPENDIX I ...................................................................................................................... 74
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
iv
Note: A separate Manual of Policies and Procedures (MOPP) developed to accompany this
protocol will provide additional details and guidance on study operational activities. A Data
Management Handbook (DMH) will provide details for data collection procedures and data
quality management procedures. Participating sites will be provided the necessary instructions
and review of the protocol, MOPP and DMH during site visits and/or at investigator meetings.
The current master protocol (incorporating any approved amendments), MOPP, and DMH are
always accessible to authorized study staff via the SCORE Study web page at
http://www.emmes.com/, where a username and password are required for access.
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
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Page 1
Précis
1
Macular edema is a major cause of vision loss in patients with central retinal vein occlusion
2
(CRVO) and branch retinal vein occlusion (BRVO). Currently, there is no effective treatment for
3
macular edema associated with CRVO. For macular edema associated with BRVO, grid laser
4
photocoagulation may be an effective treatment, but many patients derive limited benefit from
5
this treatment. Therefore, the development of new treatment modalities to treat macular edema
6
caused by these two conditions is an important research goal. The Standard Care vs.
7
COrticosteroid for REtinal Vein Occlusion (SCORE) Study will compare the efficacy and safety
8
of standard care with intravitreal injection(s) of triamcinolone acetonide to treat macular edema
9
associated with CRVO and BRVO.
10
11
The SCORE Study is designed as a multicenter, randomized, Phase III trial to compare the
12
efficacy and safety of standard care versus triamcinolone acetonide injection(s) for the treatment
13
of macular edema associated with CRVO and BRVO. In each of the two disease areas, 486
14
participants will be randomized in a 1:1:1 ratio to one of three groups: standard care, intravitreal
15
triamcinolone 4 mg, or intravitreal triamcinolone 1 mg. For CRVO participants, standard care
16
consists of observation of the macular edema. For BRVO participants, standard care consists of
17
immediate grid laser photocoagulation for study eyes without a dense macular hemorrhage. For
18
study eyes of BRVO participants with a dense macular hemorrhage, standard care is observation
19
followed by grid laser photocoagulation if and when clearing of the hemorrhage permits grid
20
laser photocoagulation. For all three groups, neovascular complications will be treated as
21
necessary. Repeat treatments will be provided as clinically indicated based on protocol-specific
22
guidelines. Participants will be followed for between 1 and 3 years after randomization. The
23
primary efficacy outcome of this study is improvement by 15 or more letters from baseline in
24
best-corrected ETDRS visual acuity score at the 12-month visit. Secondary efficacy outcomes
25
include change between baseline and each efficacy outcome assessment visit in best-corrected
26
ETDRS visual acuity score, change in retinal thickness at the center of the macula and change in
27
area of retinal thickening as assessed by stereoscopic color fundus photography, and change in
28
retinal thickness and calculated retinal thickening as assessed by optical coherence tomography.
29
Safety outcomes include injection-related adverse events such as infectious endophthalmitis,
30
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
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non-infectious endophthalmitis, retinal detachment, and vitreous hemorrhage and steroid-related
31
adverse events, which include cataract and elevated intraocular pressure.
32
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
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1.
Introduction
33
Central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) are common
34
retinal vascular diseases. Macular edema from these two conditions is a frequent cause of vision
35
loss and remains a major public health problem. Furthermore, current treatment modalities for
36
macular edema resulting from these conditions are often unsatisfactory. At present, there is no
37
effective treatment for macular edema from CRVO. Grid laser photocoagulation for macular
38
edema from BRVO may, in many cases, be an effective treatment. However, many patients
39
derive limited benefit from this treatment. A number of new treatment modalities are being
40
developed. The majority of these is either based on complex surgical procedures or is associated
41
with increased cost. The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE)
42
Study proposes to investigate the less expensive and relatively less invasive treatment of
43
intravitreal injection(s) of triamcinolone acetonide for this frequent cause of visual impairment in
44
patients with CRVO and BRVO.
45
46
The potential adverse effects of corticosteroids include cataract and elevated intraocular pressure
47
(IOP). Delivery of corticosteroids via intravitreal injection adds potential injection-related risks
48
of retinal detachment, vitreous hemorrhage, infectious endophthalmitis, and non-infectious
49
endophthalmitis. As a result of these risks, further investigation is warranted to evaluate the risks
50
of this treatment modality compared with the potential benefits. The risks associated with
51
intravitreal injection(s) of corticosteroids may be acceptable given the opportunity to reverse
52
vision loss from macular edema associated with CRVO or BRVO.
53
54
2.
Background and Scientific Justification
55
2.1 Venous Occlusive Disease
56
CRVO and BRVO are common retinal vascular disorders. BRVO has been reported to be
57
second only to diabetic retinopathy in the frequency with which it produces retinal vascular
58
disease.1 CRVO and BRVO have a characteristic appearance with intraretinal hemorrhage,
59
tortuous and dilated retinal veins and, occasionally, optic disc edema. Macular edema is a
60
frequent cause of visual acuity loss in eyes with CRVO and BRVO.1-4
61
62
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
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In the Central Vein Occlusion Study (CVOS) 728 eyes with CRVO were studied.2 Of these
63
728 eyes, 155 (21%) had macular edema that reduced visual acuity to 20/50 or worse
64
(group M eyes, macular edema). In the largest group (group P, perfused) that included 547
65
eyes, 84% (460 eyes) had angiographic evidence of macular edema involving the fovea at
66
baseline.
67
68
The natural history of macular edema associated with CRVO was delineated in the CVOS.2-4
69
Additionally, the group M arm of the CVOS evaluated the treatment of macular edema with
70
grid laser photocoagulation in 155 eyes (77 treated eyes and 78 control eyes) over a 3 year
71
follow-up period. All eyes had macular edema for a minimum of 3 months prior to
72
enrollment. For untreated eyes with an initial visual acuity between 20/50 and 5/200 at
73
presentation (n=78 eyes), 42 eyes were available for follow-up at the 3-year visit. Of these
74
eyes, 10 (24%) gained two or more lines of visual acuity at the 3-year follow-up. Twenty
75
eyes (48%) remained within two lines of baseline visual acuity and 12 eyes (29%) lost two or
76
more lines of visual acuity at the 3-year follow-up. At the 3-year follow-up, six eyes (14%)
77
gained three or more lines of visual acuity. Thirty eyes (71%) remained within three lines of
78
baseline visual acuity and six eyes (14%) lost three or more lines of visual acuity at the 3-
79
year follow-up. The final median visual acuity in untreated eyes was 20/160.
80
81
At the 2-year visit, 53 untreated eyes were available for follow-up. Of these eyes, 10 (19%)
82
gained two or more lines of visual acuity. Thirty-one eyes (58%) remained within two lines
83
of baseline visual acuity and 12 eyes (23%) lost two or more lines of visual acuity at the 2-
84
year follow-up. At the 2-year follow-up, 6 eyes (11%) gained three or more lines of visual
85
acuity. Thirty-nine eyes (74%) remained within three lines of baseline visual acuity and
86
eight eyes (15%) lost three or more lines of visual acuity at the 2-year follow-up.
87
88
At the 1-year visit, 72 untreated eyes were available for follow-up. Of these eyes, 6 (8%)
89
gained two or more lines of visual acuity. Forty-four eyes (61%) remained within two lines
90
of baseline visual acuity and 22 eyes (31%) lost two or more lines of visual acuity at the 1-
91
year follow-up. At the 1-year follow-up, 4 eyes (6%) gained three or more lines of visual
92
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
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acuity. Fifty-nine eyes (82%) remained within three lines of baseline visual acuity and nine
93
eyes (13%) lost three or more lines of visual acuity at the 1-year follow-up.
94
95
The CVOS found no significant difference in visual outcome between the treatment and
96
observation groups at any follow-up point. Although there was a definite decrease in
97
macular edema on fluorescein angiography in the treatment group when compared to the
98
control group, this did not translate to a direct visual improvement.4 Therefore, at present,
99
there is no proven therapy for visual impairment due to macular edema associated with
100
CRVO. Thus, it is important to explore other avenues for managing this potentially
101
devastating cause of vision loss.
102
103
The Branch Vein Occlusion Study (BVOS) reported on the natural history of macular
104
edema associated with BRVO.1 All eyes had macular edema for 3 to 18 months prior to
105
study entry; eyes with obvious areas of capillary nonperfusion in the macula were excluded
106
from the study. After 3 years, of 35 untreated eyes available for follow-up, only 12 eyes
107
(34%) with a presenting visual acuity of 20/40 or worse achieved a visual acuity of 20/40 or
108
better. Furthermore, eight eyes (23%) had 20/200 or worse visual acuity at the final 3-year
109
follow-up visit.
110
111
The group III arm of the BVOS was designed to evaluate grid photocoagulation treatment
112
of macular edema due to BRVO that had persisted for at least 3-months (and less than 18
113
months) in eyes with visual acuity of 20/40 or worse. One hundred thirty nine eyes (71
114
treated eyes and 68 control eyes) were studied. This arm of the study did demonstrate a
115
benefit for eyes treated with macular grid photocoagulation.1 Of 43 treated eyes available
116
for follow-up at the 3-year visit, 28 eyes (65%) had gained two or more lines of visual
117
acuity from baseline and maintained this gain for at least eight months, as compared with
118
the same gain in 13 of 35 (37%) untreated eyes. At the 3-year visit, nearly twice as large a
119
proportion of treated vs. control eyes had visual acuity of 20/40 or better.
120
121
Although the BVOS did demonstrate a visual acuity benefit for eyes treated with grid
122
photocoagulation, the BVOS also identified a subset of patients that derive limited benefit
123
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
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from macular grid photocoagulation. In the BVOS, 40% of treated eyes (n=43) had worse
124
than 20/40 vision at 3 years and 12% of treated eyes had 20/200 or worse visual acuity at 3
125
years.1 Therefore, for some patients with macula edema associated with BRVO current
126
treatment options are limited and other treatment options should be sought. For example,
127
surgical decompression of BRVO via arteriovenous crossing sheathotomy has been
128
investigated.5 However, this is an invasive surgical intervention with inherent risks,
129
recovery time and expense. As a result, there is interest in exploring treatment options such
130
as intravitreal injection(s) of triamcinolone acetonide. Table 1 summarizes visual acuity
131
data from the two randomized clinical trials discussed above in which the natural history of
132
macular edema from CRVO and BRVO was evaluated.
133
134
Table 1: Natural history of macular edema in two randomized
135
trials of patients with retinal vein occlusion
136
137
Study
Vision
improved by 2
or more lines
Vision
unchanged
(± 2 lines)
Vision worse by
2 or more lines
Number of
eyes at end
of study
period
Follow-
up period
%
No.
%
No.
%
No.
CVOS
24%
10
48%
20
29%
12
42
3 years
CVOS
19%
10
58%
31
23%
12
53
2 years
CVOS
8%
6
61%
44
31%
22
72
1 year
CVOS*
6%
4
82%
59
13%
9
72
1 year
BVOS
37%
13
46%
16
17%
6
35
3 years
* Improvement or worsening of vision by 3 or more lines
138
CVOS Central Vein Occlusion Study
139
BVOS Branch Vein Occlusion Study
140
141
2.2 Pathogenesis of Macular Edema
142
Macular edema from venous occlusive disease results from the initial insult of thrombus
143
formation at the lamina cribrosa or an arteriovenous crossing. Green et al, in a
144
histopathologic study of 29 eyes with CRVO, documented a fresh or recanalized thrombus
145
of the central retinal vein in the area of the lamina cribosa as a constant pathologic finding.6
146
Frangieh et al, in a histopathologic study of nine eyes with BRVO, documented a fresh or
147
recanalized thrombus at the site of vein occlusion in all eyes studied.7 Experimental work in
148
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animals has demonstrated that following venous occlusion, a hypoxic environment in the
149
retina is produced.8 This is then followed by functional, and later structural changes, in the
150
retinal capillaries. These changes resulted in an immediate increase in retinal capillary
151
permeability and accompanying retinal edema.
152
153
The increase in retinal capillary permeability and subsequent retinal edema may be the
154
result of a breakdown of the blood retina barrier mediated in part by vascular endothelial
155
growth factor (VEGF), a 45 kD glycoprotein.9 Aiello et al demonstrated in an in vivo
156
model, that VEGF can increase vascular permeability.9 Fifteen eyes of 15 albino Sprague-
157
Dawley rats received an intravitreal injection of VEGF. The effect of intravitreal
158
administration of VEGF on retinal vascular permeability was assessed by vitreous
159
fluorophotometry. In all 15 eyes which received an intravitreal injection of VEGF, a
160
statistically significant increase in vitreous fluorescein leakage was recorded. In contrast,
161
control eyes, which were fellow eyes injected with vehicle alone, did not demonstrate a
162
statistically significant increase in vitreous fluorescein leakage. Vitreous fluorescein
163
leakage in eyes injected with VEGF attained a maximum of 227% of control levels.
164
Antonetti et al demonstrated that VEGF may regulate vessel permeability by increasing
165
phosphorylation of tight junction proteins such as occludin and zonula occluden 1.10
166
Sprague-Dawley rats were given intravitreal injections of VEGF and changes in tight
167
junction proteins were observed through Western blot analysis. Treatment with alkaline
168
phosphatase revealed that these changes were caused by a change in phosphorylation of
169
tight junction proteins. This model provides, at the molecular level, a potential mechanism
170
for VEGF-mediated vascular permeability in the eye. Similarly, in human non-ocular
171
disease states such as ascites, VEGF has been characterized as a potent vascular
172
permeability factor (VPF).11
173
174
The normal human retina contains little or no VEGF; however, hypoxia causes
175
upregulation of VEGF production.12 Disease states characterized by hypoxia-induced
176
VEGF upregulation include CRVO and BRVO.9,12 Vinores et al, using
177
immunohistochemical staining for VEGF, demonstrated that increased VEGF staining was
178
found in retinal neurons and retinal pigment epithelium in human eyes with venous
179
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occlusive disease.12 Pe’er et al, evaluated 10 human eyes enucleated for neovascular
180
glaucoma from CRVO and used molecular localization with a VEGF-specific probe to
181
identify cells producing VEGF messenger RNA (mRNA).13 All of these eyes demonstrated
182
upregulated VEGF mRNA expression in the retina. This hypoxia-induced upregulation of
183
VEGF may be inhibited pharmacologically. Adamis et al demonstrated in a nonhuman
184
primate model that anti-VEGF antibodies can inhibit VEGF driven capillary endothelial
185
cell proliferation.14 In this study, 16 eyes of nonhuman primates had retinal ischemia
186
induced by laser retinal vein occlusion. Zero of eight eyes receiving neutralizing anti-
187
VEGF antibodies developed iris neovascularization while five of eight control eyes
188
eventually developed iris neovascularization.
189
190
As the above discussion suggests, attenuation of the effects of VEGF introduces a rationale
191
for treatment of macular edema from venous occlusive disease. Corticosteroids, a class of
192
substances with anti-inflammatory properties, have been demonstrated to inhibit the
193
expression of the VEGF gene.15 In a study by Nauck et al, the platelet-derived growth-
194
factor (PDGF) induced expression of the VEGF gene in cultures of human aortic vascular
195
smooth muscle cells was inhibited by corticosteroids in a dose-dependent manner.15 A
196
separate study by Nauck et al demonstrated that corticosteroids downregulated the
197
induction of VEGF by the pro-inflammatory mediators PDGF and platelet-activating factor
198
(PAF) in a time and dose-dependent manner.16 This study was performed using primary
199
cultures of human pulmonary fibroblasts and pulmonary vascular smooth muscle cells.
200
201
2.3 Animal and Clinical Studies Using Intravitreal Triamcinolone Acetonide
202
Injections
203
Intravitreal injection of triamcinolone acetonide has been shown to be non-toxic in animal
204
studies.17-19 McCuen et al injected 1mg of triamcinolone acetonide into the vitreous cavity
205
of 21 rabbit eyes.17 Throughout the 3-month course of follow-up ophthalmoscopy, IOP,
206
electroretinography (scotopic and photopic responses) and light and electron microscopy all
207
remained normal. Schindler et al studied the clearance of intravitreally injected
208
triamcinolone acetonide (0.5 mg) in 30 rabbit eyes.18 In non-vitrectomized eyes the average
209
clearance rate was 41 days. In eyes having undergone vitrectomy or combination
210
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vitrectomy and lensectomy the average clearance rate was 17 days and 7 days,
211
respectively.18 It was found that the ophthalmoscopic disappearance of injected
212
triamcinolone acetonide correlated well with a spectrophotometric analysis for clearance of
213
the drug. Scholes et al also studied the clearance of intravitreally injected triamcinolone
214
acetonide (0.4 mg) in 24 rabbit eyes.19 Using high-performance liquid chromatography
215
(HPLC) complete clearance of the drug was noted by 21 days. Non-detectable drug levels
216
(by HPLC) were present before ophthalmoscopic disappearance.
217
218
As discussed above, corticosteroids have been experimentally shown to downregulate
219
VEGF production and possibly reduce breakdown of the blood-retinal barrier.15,16
220
Similarly, steroids have antiangiogenic properties possibly due to attenuation of the effects
221
of VEGF.20,21 These properties of steroids are commonly utilized. Clinically,
222
triamcinolone acetonide is used locally as a periocular injection for the treatment of cystoid
223
macular edema (CME) secondary to uveitis or as a result of intraocular surgery.22,23 In
224
animal studies, intravitreal triamcinolone acetonide has been used in the prevention of
225
proliferative vitreoretinopathy24,25 and retinal neovascularization.26,27 Intravitreal
226
triamcinolone acetonide has been used clinically in the treatment of proliferative
227
vitreoretinopathy28 and choroidal neovascularization.29-31
228
229
Recently, intravitreal triamcinolone acetonide has been used clinically in the treatment of
230
retinal vascular disease. A case report by Jonas and Sofker describes a patient with non-
231
proliferative diabetic retinopathy with a 6-month history of persistent, diffuse macular
232
edema despite grid photocoagulation.32 Following one intravitreal injection of
233
triamcinolone acetonide (20mg) the visual acuity of this patient improved from 20/200 to
234
20/50 over a 5-month follow-up period. It was also noted that there was marked regression
235
of macular edema on clinical examination.
236
237
Martidis et al conducted a pilot study of 16 eyes with macular edema due to diabetic
238
retinopathy.33,34 All 16 eyes demonstrated persistent macular edema involving the center of
239
the macula despite each eye receiving two to six sessions of focal/grid laser
240
photocoagulation. In 11 eyes with a known time of onset of macular edema, the average
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duration of macular edema was 32 months (range, 13 to 68 months) prior to intravitreal
242
triamcinolone acetonide injection. The other five eyes were known to have macular edema
243
for at least 6 months. All 16 eyes were treated with intravitreal triamcinolone acetonide
244
injection and the results are summarized in Tables 2a and 2b.
245
246
Baseline central foveal thickness averaged 540 microns for the 16 enrolled eyes when
247
measured by optical coherence tomography. For 14 eyes evaluated at 1-month, mean
248
foveal thickness decreased from 533 microns to 242 microns. Two eyes did not complete
249
the 1-month follow-up examination. Fourteen eyes evaluated at 3-months showed a
250
reduction in mean foveal thickness from 528 microns to 224 microns. Two eyes did not
251
complete the 3-month examination; these were different eyes than those that did not
252
complete the 1-month examination. Eight eyes completing six months of follow-up
253
showed a reduction in mean foveal thickness from 540 microns to 335 microns.
254
255
Mean Snellen visual acuity improved by 2.4, 2.4, and 1.3 lines at the 1, 3, and 6-month
256
follow-up intervals, respectively. No eyes lost vision at 1-month and all but one eye
257
showed improvement ranging from one to five lines; nine of 14 (64%) eyes showed
258
improvement of two or more lines at this interval. No eyes lost vision from baseline at 3-
259
months, and all but one eye showed improvement ranging from one to five lines; nine of 14
260
(64%) eyes showed improvement of two or more lines at the 3-month interval. One eye
261
lost a single line from baseline at six months and one eye remained stable; the other six
262
eyes maintained improved visual acuity ranging from one to three Snellen lines. Four of
263
eight (50%) eyes maintained a visual acuity improvement of two or more lines from
264
baseline at the 6-month follow-up.
265
266
Five of 14 eyes that were evaluated at the 1-month follow-up had an IOP that exceeded 21
267
mmHg. The IOP in all five eyes was controlled successfully with one topical aqueous
268
suppressant. Two of 14 eyes that were evaluated at the 3-month follow-up had an IOP that
269
exceeded 21 mmHg. The IOP in both eyes was controlled successfully with one topical
270
aqueous suppressant. One of eight eyes that were evaluated at the 6-month follow-up had
271
an IOP that exceeded 21 mmHg. The IOP in this eye was controlled successfully with one
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topical aqueous suppressant. The average IOP increased 45%, 20% and 13% from baseline
273
at the 1, 3 and 6-month follow-up intervals, respectively.
274
275
Three of the eight eyes completing at least 6 months of follow-up were re-injected 6 months
276
after initial injection due to recurrence of macular edema. Cataract progression that did not
277
require surgery was noted in one eye at the 6-month follow-up. No complications such as
278
retinal detachment, endophthalmitis or vitreous hemorrhage were noted in this study.
279
280
Greenberg and Martidis studied both eyes of one patient with bilateral diffuse macular
281
edema secondary to CRVO.35 The right eye of this 80 year old patient had macular edema
282
from a CRVO of 9 months duration when the patient presented with a 2-week history of
283
visual acuity loss due to macular edema from a CRVO in the left eye. Because of the poor
284
natural history of untreated macular edema in the right eye of this patient, the left eye
285
received an intravitreal injection of triamcinolone acetonide. It did well both anatomically
286
and functionally, with visual acuity improvement from 20/400 to 20/30 after three months
287
of follow-up. Central foveal thickness as measured by optical coherence tomography
288
decreased from 589 microns to 160 microns with restoration of a normal foveal contour
289
following treatment. Six months following injection, visual acuity decreased to 20/400
290
because of recurrence of retinal thickening that measured 834 microns by optical coherence
291
tomography. A second injection was performed and, 1 month later, visual acuity returned to
292
20/50 with a decrease in central foveal thickness to 158 microns with a normal foveal
293
contour. This patient has maintained this level of visual acuity for over 6 months following
294
the second injection. Given the response to treatment in the left eye, the right eye (now
295
with 16 months of untreated macular edema) was treated with an intravitreal injection of
296
triamcinolone acetonide. There was a prompt reduction in central foveal thickness as
297
measured by optical coherence tomography from 735 microns to 195 microns. However,
298
possibly as a result of the duration of macular edema, no visual benefit was noted. No
299
significant elevation of IOP was noted in either eye.
300
301
Other clinical case reports by Ip et al and Jonas et al have demonstrated similar results in
302
the treatment of macular edema due to CRVO with intravitreal injections of triamcinolone
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acetonide.36,37 Recently, Park et al evaluated intravitreal triamcinolone injection(s) as a
304
treatment of macular edema associated with CRVO.38 Ten eyes of 9 patients with perfused
305
CRVO with visual acuity 20/50 or worse were treated with an intravitreal injection of
306
triamcinolone acetonide (4mg/0.1cc). One patient received a repeat injection. The mean
307
duration from time of diagnosis to the intravitreal triamcinolone injection was 15.4 months.
308
The mean best-corrected visual acuity improved from 58 letters (range, 37-72) at baseline
309
to 78 letters (range 50-100 letters) at last follow-up (mean, 4.8 months). Volumetric optical
310
coherence tomography (VOCT) was performed on 9 of 10 patients at baseline and follow-
311
up. VOCT measurements improved from a mean of 4.2 mm3 at baseline to a mean of 2.6
312
mm3 at last follow-up (normal range of VOCT is 2.0-2.5 mm3). Three eyes without a
313
previous history of glaucoma required topical antiglaucoma medication. One eye with a
314
previous history of open-angle glaucoma required trabeculectomy surgery.
315
316
Table 3 lists the frequency and nature of adverse effects seen in some of the largest clinical
317
studies thus far using intravitreal triamcinolone acetonide. Penfold and Challa studied 30
318
eyes with exudative macular degeneration.29,30 No adverse events such as retinal
319
detachment, vitreous hemorrhage or endophthalmitis were noted. However, three of four
320
eyes that received a second injection of triamcinolone acetonide experienced rapid
321
progression of cataract within 2 months of re-injection. Two of these four eyes also
322
experienced steroid-induced glaucoma with IOP elevation to 37 mmHg. Both eyes had
323
argon laser trabeculoplasty and were treated with topical aqueous suppressants. One of
324
these two eyes required trabeculectomy surgery to control IOP. In another series, Danis et
325
al injected 16 eyes with exudative macular degeneration.31 No adverse events such as
326
retinal detachment, vitreous hemorrhage or endophthalmitis were noted. Four of seven
327
phakic patients developed progressive lens opacities that over the 6-month follow-up did
328
not require cataract surgery. Four patients developed transient IOP elevation that required
329
one to two topical aqueous suppressants to lower the intraocular pressure to less than 25
330
mmHg; all patients eventually had topical therapy discontinued. No patient had IOP over
331
32 mmHg at any point in follow-up.
332
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The other studies listed in Table 3 all demonstrate a similar adverse event profile.28,39-41 A
334
summary of the data from the seven studies listed shows that the frequency of injection-
335
related adverse events such as endophthalmitis, non-infectious endophthalmitis, retinal
336
detachment and vitreous hemorrhage appear rare based on these small studies in the
337
published literature. Corticosteroid-related adverse events, from the data in Table 3, are
338
more common. However, corticosteroid-related adverse events (cataract and elevated IOP)
339
appear to be manageable. For example, of the 221 patients in the seven studies discussed,
340
33 patients (15%) were noted to have some elevation of IOP; all patients were managed
341
successfully with topical aqueous suppressants except one patient who required argon laser
342
trabeculoplasty and one patient who required both argon laser trabeculoplasty and
343
trabeculectomy. Nine patients (4%) required cataract surgery and 24 patients (12%) were
344
noted to have progressive lens opacity.
345
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Table 2a: Clinical characteristics of sixteen patients treated with intravitreal
347
triamcinolone injection for diabetic macular edema not responsive to
348
focal/grid photocoagulation
349
350
Case
Eye
Age
Lens
Retinopathy
Duration
ME (mo)
Prior
Laser
1
OS
72
Pseudo
NPDR
21
2
2
OD
48
Phakic
PDR
36
2
3
OS
85
Phakic
NPDR
29
3
4
OS
76
Phakic
NPDR
13
2
5
OS
70
Pseudo
NPDR
23
3
6
OD
68
Phakic
NPDR
47
5
7
OD
70
Phakic
PDR
>6
2
8
OD
59
Phakic
NPDR
>6
2
9
OS
67
Phakic
NPDR
26
2
10
OD
52
Phakic
PDR
68
3
11
OS
71
Pseudo
NPDR
50
6
12
OS
74
Phakic
NPDR
12
2
13
OS
62
Phakic
NPDR
>6
2
14
OS
65
Phakic
NPDR
24
2
15
OD
43
Phakic
NPDR
>6
2
16
OD
62
Phakic
NPDR
>6
2
351
Table 2b: Clinical characteristics of sixteen patients treated with intravitreal
352
triamcinolone injection for diabetic macular edema not responsive to
353
focal/grid photocoagulation
354
355
Visual Acuity
OCT (microns)
IOP (mmHg)
F/U
Reinject
Initial
1 mo
3 mo
6 mo
Initial 1 mo
3 mo
6 mo Initial 1 mo 3 mo
6 mo (mo)
(mo)
20/400
20/200
20/200
20/200
612
378
214
236
14
24
18
16
12
No
20/80
20/50
20/60
20/100
569
171
132
519
16
20
18
16
11
11
20/200
20/60
20/60
20/60
550
177
181
208
18
12
14
20
11
No
20/400
20/200
20/100
20/100
401
232
199
174
17
22
33
16
10
No
20/400
20/200
20/400
557
154
621
15
28
14
9
6
20/200
20/80
20/100
583
109
90
15
17
23
8
No
20/400
20/60
20/100
703
264
588
14
21
16
7
6
20/60
20/30
20/30
20/40
348
268
270
242
10
17
13
13
6
No
20/800
20/100
20/100
564
397
360
17
17
22
5
No
20/80
20/60
20/60
585
199
188
15
18
15
4
No
20/200
20/200
20/100
510
260
265
12
17
11
3
No
20/400
20/400
596
233
14
14
3
No
20/200
20/60
20/40
497
213
180
12
30
16
3
No
20/200
20/60
20/60
497
239
424
15
16
20
3
No
20/200
20/40
20/40
20/40
674
262
204
17
20
16
3
No
20/100
20/50
20/40
399
180
176
14
36
20
3
No
356
NPDR: non-proliferative diabetic retinopathy
357
PDR:
proliferative diabetic retinopathy
358
ME:
macular edema
359
Pseudo: pseudophakic
360
OCT:
optical coherence tomography
361
IOP:
intraocular pressure
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Table 3:
Summary of adverse events from seven case series using intravitreal triamcinolone acetonide
363
364
# Eyes treated
Disease
Dose
(mg)
IOP rise
Cataract
(surgery)
Lens
Opacity
R.D.
Vit
Heme
Endophth
Non-infectious
endophthalmitis
Wingate39
113
AMD
4
12
NA
NA
NA
NA
NA
NA
Penfold29
30
AMD
4
3
9
1
0
0
0
0
Danis31
16
AMD
4
4
0
4/7
phakic
0
0
0
0
Jonas28
16
PVR
10-20
0
0
0
0
0
0
1
Martidis33
16
DME
4
5
0
1
0
0
0
0
Jonas40
4
NVG
20
0
0
0
0
0
0
0
Jonas41
26
DME
25
9
0
18/18 phakic
(P=.16)
0
0
0
0
7 Studies
(pooled)
221
33 (15%)
9 (4%)
24 (12%)
0
0
0
1
365
AMD
Age-related macular degeneration
366
DME
Diabetic macular edema
367
PVR
Proliferative vitreoretinopathy
368
NVG
Neovascular glaucoma
369
RD
Retinal detachment
370
NA
Not available; these adverse events were not specifically discussed in the manuscript
371
372
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2.4 Other Studies Evaluating Corticosteroid Preparations Other Than
374
Triamcinolone Acetonide for Treatment of Macular Edema due to Retinal
375
Vascular Disease
376
2.4.1 Efficacy
377
2.4.1.1 Control Delivery Systems (Bausch and Lomb)
378
Control Delivery Systems (Bausch and Lomb) is developing a non-
379
biodegradable, implantable, extended release product that delivers the
380
corticosteroid fluocinolone acetonide directly to the posterior segment of the
381
eye for a period of 3 years. A multi-center, randomized, masked trial is
382
currently being conducted to evaluate this technology for the treatment of
383
diabetic macular edema refractory to prior laser photocoagulation. Eligible
384
visual acuity was between 20/50 to 20/400, inclusive. This trial enrolled 80
385
patients with diabetic macular edema. Patients were randomly assigned to one
386
of three treatment arms: 0.5 mg implant (N=41), 2 mg implant (N=11) or
387
standard of care treatment consisting of either repeat laser photocoagulation or
388
observation (N=28). (The 6-month data shown below were presented at the
389
combined Vitreous Society and Retina Society Meeting, San Francisco, CA on
390
September 30, 2002. The 12-month data presented below were presented at
391
the Association for Research in Vision and Ophthalmology Meeting, Ft.
392
Lauderdale, FL on May 8, 2003).
393
• At the 6-month follow-up, the proportion of eyes with maintained or
394
improved visual acuity was greater in eyes that received the 0.5 mg
395
implant than those assigned to standard of care treatment (P<0.01).
396
This result was not statistically significant at the 12-month follow-up.
397
• At the 6-month follow-up, the proportion of eyes with a two or more
398
step decrease in retinal thickening at the center of the fovea was greater
399
in eyes that received the 0.5 mg implant than those assigned to
400
standard of care treatment (P=0.026). This result remained statistically
401
significant at the 12-month follow-up (P=0.003).
402
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2.4.1.2 Oculex
404
Oculex is developing a biodegradable, implantable, extended release product
405
(Posurdex) that delivers the corticosteroid dexamethasone directly to the
406
posterior segment of the eye for a period of 35 days. A phase two clinical trial
407
was completed evaluating two dosages of Posurdex, 350 micrograms and 700
408
micrograms. Patients with macular edema due to diabetic retinopathy, retinal
409
vascular occlusive disease, Irvine-Gass syndrome or uveitis were included.
410
Eligible visual acuity was 20/40-20/200. Patients were randomized to one of
411
three treatment arms: 350 microgram implant, 700 microgram implant or
412
observation. 306 patients were enrolled, 172 with diabetic macular edema,
413
103 with vein occlusion, 27 with Irvine-Gass syndrome and 14 with uveitic
414
macular edema.
415
• Patients receiving the 700 microgram implant had a statistically
416
significant improvement in visual acuity of two or more lines on the
417
ETDRS chart when compared to patients who did not receive the
418
implant (P=0.019).
419
• Secondary outcomes such as retinal thickness and fluorescein leakage
420
also showed statistically significant decreases in patients that received
421
the 700 microgram implant when compared to patients who did not
422
receive the implant (P=0.001).
423
• Patients receiving the 350 microgram implant also demonstrated
424
statistically significant decreases in retinal thickness and fluorescein
425
leakage, with a trend towards improvement in visual acuity, indicating
426
a dose response to the treatment.
427
428
2.4.2 Adverse Effects
429
2.4.2.1 Control Delivery Systems (Bausch and Lomb)
430
Elevated IOP
431
• At the 6-month follow-up, 12.2% of patients in the 0.5 mg implant
432
group had an IOP elevation to 30 mmHg or more. All patients were
433
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managed with topical antiglaucoma medication. No eye in the
434
standard of care group had such an elevation in IOP.
435
• At the 12-month follow-up, 19.5% of patients in the 0.5 mg implant
436
group had an IOP elevation that was considered a serious adverse
437
event. Three patients in the 0.5 mg implant group required
438
trabeculectomy surgery. No eye in the standard of care group had such
439
an elevation in IOP.
440
Cataract
441
• At the 6-month follow-up, 0.0% of patients in the standard of care
442
group had “cataract progression”. Seventeen percent of patients in the
443
0.5 mg group had “cataract progression.
444
• At the 12-month follow-up, 0.0% of patients in the standard care group
445
had cataract progression defined as a serious adverse event. Forty-one
446
percent of patients in the 0.5 mg group (all study eyes) had cataract
447
progression defined as a serious adverse event.
448
449
2.4.2.2 Oculex
450
Elevated IOP
451
•
An IOP elevation to 25 mmHg or more was noted at some point in
452
the study in 32 eyes; all were readily controlled with topical
453
antiglaucoma medication.
454
Cataract and other side effects
455
•
There was no difference in cataract progression between the study
456
groups.
457
•
No other safety concerns were noted.
458
459
2.5 Rationale for the Intravitreal Triamcinolone Acetonide Doses to be Evaluated
460
The optimal dose of triamcinolone acetonide to maximize efficacy with minimum side
461
effects is not known. A 4 mg dose of Kenalog, a commercially available preparation that is
462
FDA labeled for intramuscular or intrabursal use, is principally being used in clinical
463
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practice. However, this dose has been used based on feasibility rather than scientific
464
principles.
465
466
There is also experience using doses of 1 mg and 2 mg. These doses anectodally have been
467
reported to reduce macular edema. There is a rationale for using a dose lower than 4
468
mg.42,43 Glucocorticoids bind to glucocorticoid receptors in the cell cytoplasm, and the
469
steroid-receptor complex moves to the nucleus where it regulates gene expression. The
470
steroid-receptor binding occurs with high affinity (low dissociation constant (Kd) which is
471
on the order of 5 to 9 nanomolar). Complete saturation of all the receptors occurs at about
472
20 fold higher levels, so about 100 nanomolar. A 4 mg dose of triamcinolone/4mg of
473
vitreous volume yields a final concentration of 7.5 millimolar, or nearly 10,000 fold more
474
than the saturation dose. Thus, the effect of a 1 mg dose may be equivalent to that of a 4mg
475
dose, because compared to the 10,000 fold saturation, a 4-fold difference in dose is
476
inconsequential. It is also possible that higher doses of corticosteroid could be less
477
effective than lower doses due to down-regulation of the receptor. The steroid implant
478
studies provide additional justification for evaluating a lower dose—a 0.5 mg device which
479
delivers only 0.5 micrograms per day has been observed to have a rapid effect in reducing
480
macular edema (P. Andrew Pearson, personal communication).
481
482
There has been limited experience using doses greater than 4 mg. Jonas’ case series
483
described earlier reported results using both a 20mg and a 25mg dose. However, others
484
have not been able to replicate this dose using the preparation procedure described by Jonas
485
(Frederick Ferris, personal communication).
486
487
In the SCORE Study, 4 mg and 1 mg doses will be evaluated. The former because it is the
488
dose that is currently most commonly used in clinical practice and the latter because there is
489
reasonable evidence for efficacy and the potential for lower risk. Although there is good
490
reason to believe that a 1 mg dose will reduce macular edema, it is possible that the
491
retreatment rate will be higher with this dose compared with 4 mg since the latter will
492
remain active in the eye for a longer duration than the former. Insufficient data are
493
available to warrant evaluating a dose higher than 4mg at this time.
494
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495
2.6 Mechanism of Adverse Effects Associated with Intravitreal Steroids
496
2.6.1 Elevation of Intraocular Pressure
497
IOP depends on the comparative rates of aqueous production and aqueous drainage,
498
primarily through the trabecular meshwork. Increased IOP occurs from a variety of
499
mechanisms such as primary or secondary angle-closure glaucoma, primary or
500
secondary open-angle glaucoma, or combined-mechanism glaucoma. If inadequately
501
treated, increased IOP may result in glaucomatous optic nerve changes and loss of
502
visual field.
503
504
Among the secondary open-angle glaucomas, corticosteroid-induced elevation of IOP
505
is one of the most common. This relationship is well established. In patients
506
susceptible to this phenomenon, the elevation of IOP may occur as a result of topical,
507
systemic or peribulbar administration. For example, following 4-6 weeks of topical
508
corticosteroid administration, 5% of subjects may show an elevation in IOP of
509
>16mmHg and 30% of subjects may show an elevation of 6-15mmHg.44,45
510
511
The mechanism of corticosteroid induced elevation of IOP is incompletely
512
understood. Possible theories include46: a) inhibition of the production of outflow-
513
enhancing prostaglandins, b) suppression of trabecular meshwork endothelial cell
514
phagocytosis, c) increased deposition of proteoglycans or glycosaminoglycans in the
515
trabecular meshwork with a resultant increase in resistance to outflow, d) increase in
516
cross-linked actin networks in the trabecular meshwork, e) increase in the expression
517
of cellular tight-junction protein, f) stabilization of lysosomes which allow
518
accumulation of hyaluronate or other debris in the trabecular meshwork.
519
520
The intravitreal administration of corticosteroid is expected to be associated with an
521
increase in IOP in susceptible patients. Indeed, the literature reviewed in this protocol
522
confirm that corticosteroid induced elevation in IOP may result from intravitreal
523
corticosteroid administration (Table 3). The time course for the development of
524
corticosteroid induced elevation in IOP as a result of intravitreal injection is presently
525
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unknown. Additionally, the effect of the initial dose administered, the frequency of
526
reinjection or the cumulative dose administered over time on the severity of IOP
527
elevation is not known. The experience thus far indicates that the 4 mg and 25 mg
528
doses of triamcinolone acetonide appear to result in a relatively similar frequency and
529
severity of IOP elevation 33,41 Reinjection of the 4 mg dose at a frequency of more
530
than once every four months appears to be associated with more frequent and more
531
severe elevation in IOP.29
532
533
All patients who receive intravitreal injection of corticosteroid will have IOP
534
monitored carefully in this study. The frequency and severity of IOP elevation will be
535
monitored.
536
537
2.6.2 Cataract Formation
538
An opacity of the lens that results in loss of transparency and/or causes light scatter is
539
called a cataract. The reasons why cataracts occur include: formation of opaque
540
fibers, fibrous metaplasia, epithelial opacification, accumulation of pigment and
541
formation of extracellular materials. These changes can occur as a result of the aging
542
process, trauma, radiation, electric shock, in association with systemic disorders, or as
543
a result of drugs or chemicals. The most common types of cataract are cortical,
544
nuclear and posterior subcapsular.47 In cortical cataracts, the soluble protein content
545
decreases and results in lens alteration. Nuclear cataracts may form as a result of an
546
increase in insoluble protein content along with the accumulation of chromophores.
547
Posterior subcapsular cataracts are caused by dysplastic changes in germinal
548
epithelium. These dysplastic cells migrate posteriorly and give rise to bladder cells of
549
Wedl, resulting in posterior subcapsular opacity.
550
551
Among the toxic causes of cataract, corticosteroid-induced cataract is one of the most
552
common. The relationship between dose and duration of exposure to the formation of
553
cataract is unclear. However, the association between corticosteroids and cataract is
554
well established. Corticosteroid induced cataracts typically show an axial, posterior
555
subcapsular opacity which gradually increases in size. Topical, systemic and
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peribulbar corticosteroid administration have all been associated with an increased
557
risk of cataract formation.48 Even the prolonged administration of inhaled
558
corticosteroids has been associated with an increased risk of cataract formation.49
559
560
The intravitreal administration of corticosteroid is also expected to be associated with
561
cataract formation. Indeed, the literature reviewed in this protocol confirms that
562
cataracts appear to result from intravitreal corticosteroid administration (Table 3).
563
The time course for the development of cataract as a result of intravitreal
564
corticosteroid injection is presently unknown. However, it is believed that the
565
formation of cataract in response to intravitreal administration is gradual and takes
566
place over the course of approximately 1 year. As with other routes of corticosteroid
567
administration, posterior subcapsular cataract appears to be the most common type of
568
cataract to form following the intravitreal administration of corticosteroid. Table 3
569
shows that 4% of patients in the 7 pooled studies required cataract surgery and 12%
570
had progressive lens opacity. These studies had at least 3 months of follow-up and, in
571
some cases, substantially more.
572
573
Corticosteroid induced cataract will be followed closely as an adverse event in this
574
study.
575
576
2.6.3 Endophthalmitis
577
Infectious endophthalmitis is an intraocular inflammatory process due to infection
578
with pathogens such as bacteria or fungi. Clinical features include lid edema,
579
conjunctival injection, corneal edema, anterior chamber and vitreous inflammation,
580
and hypopyon. Infectious endophthalmitis can occur following an intraocular
581
procedure (e.g. cataract surgery, vitrectomy surgery, intravitreal injection), as a result
582
of systemic infection, as a result of trauma, or occur as a late feature of conjunctival
583
filtering blebs.
584
585
Acute postoperative endophthalmitis following cataract surgery is the most common
586
cause. The overall incidence, however, is low and in one survey the incidence
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following cataract surgery was <1%.50 In the Endophthalmitis Vitrectomy Study
588
(EVS), gram-positive organisms accounted for 94% of culture positive cases.51
589
590
The incidence and causative pathogens following intravitreal injection of
591
corticosteroid are less well defined. In the published literature, this complication
592
appears uncommon (Table 3). Endophthalmitis following intravitreal injection of
593
antiviral agents for the treatment of CMV retinitis also appears to be uncommon
594
(personal communication, Daniel F. Martin). However, the injection of a bolus of
595
medication that has immunosuppressive properties may result in a higher incidence of
596
postinjection endophthalmitis using corticosteroids. A standardized protocol to
597
prepare eyes for the injection procedure may help to decrease the incidence of this
598
complication. Such a protocol is described in the Manual of Procedures and
599
Procedures (MOPP).
600
601
The clinical experience to date has been with the use of Kenalog. Kenalog is a
602
commercially available preparation that is FDA labeled for intramuscular or
603
intrabursal use. The available preparation of Kenalog contains, in addition to
604
triamcinolone acetonide, 0.99% benzyl alcohol, 0.75% carboxymethylcellulose
605
sodium and 0.04% polysorbate 80.52 Although the published literature to date does
606
not describe a significant incidence of complications as a result of the Kenalog
607
vehicle, anecdotal experience suggests that there may be a significant incidence of
608
non-infectious endophthalmitis as a result of the vehicle components [American
609
Society of Retinal Specialists listserve from 2002-2003]. As a result of the possibility
610
of a sterile reaction to the components of the Kenalog vehicle, it is difficult to be
611
certain if an inflammatory reaction is infectious or non-infectious following an
612
injection of Kenalog. Treatment of infectious endophthalmitis requires immediate
613
treatment with intravitreal antibiotics with or without vitrectomy surgery depending
614
on the clinical situation. Non-infectious endophthalmitis is usually self-limiting. A
615
sterile, preservative-free triamcinolone preparation will be used in this study.
616
617
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Despite the use of a sterile, preservative-free preparation, inflammatory reactions
618
following intravitreal injection as well as the frequency of infectious endophthalmitis
619
will be monitored carefully in this study.
620
621
3.
Objectives
622
The primary objective of the SCORE Study is to compare visual acuity outcome among 3 groups
623
of participants: those who are randomly assigned to receive standard care and those randomly
624
assigned to receive one of two doses of intravitreal injection(s) of triamcinolone acetonide for
625
treatment of macular edema associated with CRVO and BRVO. Secondary objectives include
626
estimating the incidence of infectious endophthalmitis, non-infectious endophthalmitis, retinal
627
detachment, vitreous hemorrhage, cataract and elevated IOP in eyes receiving intravitreal
628
injection(s) of triamcinolone. Other secondary objectives include comparing changes in retinal
629
thickness and calculated retinal thickening in participants who are randomly assigned to receive
630
intravitreal injection(s) of triamcinolone acetonide with those randomly assigned to standard care
631
for treatment of macular edema associated with CRVO and BRVO.
632
633
4.
Study Design and Methods
634
The SCORE Study is a multicenter, randomized, Phase III trial designed to compare the efficacy
635
and safety of standard care with intravitreal injection(s) of triamcinolone acetonide for the
636
treatment of macular edema associated with CRVO and BRVO. Eligible participants within each
637
of these two disease entities will be randomized in a 1:1:1 ratio to one of three groups (treatment
638
of neovascular complications as necessary in all three groups):
639
1. Standard care group: conventional treatment consisting of:
640
a. CRVO:
641
i.
Observation of macular edema.
642
b. BRVO:
643
i.
Study eyes with dense macular hemorrhage: Immediate observation. Grid
644
laser photocoagulation will be performed if and when clearance of hemorrhage
645
permits grid laser photocoagulation.
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ii.
Study eyes without dense macular hemorrhage: Immediate grid laser
647
photocoagulation.
648
or
649
2. Intravitreal injection(s) of 4 mg of triamcinolone acetonide,
650
or
651
3. Intravitreal injection(s) of 1 mg of triamcinolone acetonide.
652
653
Note: Patients and investigators will be masked to the triamcinolone acetonide dose used (1
654
mg or 4 mg).
655
656
4.1 Efficacy Assessment
657
4.1.1 Primary Efficacy Outcome
658
The primary efficacy outcome of this study is improvement by 15 or more letters from
659
baseline in best-corrected ETDRS visual acuity score at the 12-month visit as
660
determined by the ETDRS visual acuity protocol. The primary outcome analysis will
661
include the following three comparisons of the proportion of participants having a 15
662
ETDRS letter improvement from baseline to 1 year:
663
• 4 mg triamcinolone acetonide intravitreal injections with standard care
664
• 1 mg triamcinolone acetonide intravitreal injections with standard care
665
• 4 mg triamcinolone acetonide intravitreal injections with 1 mg triamcinolone
666
acetonide intravitreal injections
667
668
4.1.2 Secondary Efficacy Outcomes
669
Secondary efficacy outcomes include the following:
670
•
Change between baseline and each efficacy outcome assessment visit in
671
best-corrected ETDRS visual acuity score (e.g., mean change from baseline
672
in visual acuity, distribution of change from baseline in visual acuity based
673
on clinically meaningful cut points of improvement or worsening of visual
674
acuity).
675
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•
Change in calculated retinal thickening as assessed by optical coherence
676
tomography.
677
•
Change in retinal thickness at the center of the macula as assessed by
678
stereoscopic color fundus photography.
679
•
Change in area of retinal thickening as assessed by stereoscopic color fundus
680
photography.
681
682
4.2 Safety Assessments
683
4.2.1 Safety Outcomes
684
Safety outcomes will be tabulated by observing the nature, severity and frequency of
685
adverse events throughout the three years of the study. Specific safety outcomes
686
include:
687
•
Injection-related events including infectious endophthalmitis, non-infectious
688
endophthalmitis, retinal tear or detachment, vitreous hemorrhage, ocular
689
discomfort/irritation, ocular tenderness, ocular itching sensation, foreign
690
body sensation, blurred vision, floaters, corneal abrasion, subconjunctival
691
hemorrhage, conjunctival edema, and conjunctival hyperemia/erythema.
692
•
Steroid-related toxicities including cataract and elevated IOP.
693
694
4.3 Inclusion Criteria
695
4.3.1 General Inclusion Criteria
696
a.
Ability and willingness to provide informed consent.
697
b.
Sex: Participants may be male or female.
698
c.
Age: 18 years or older
699
700
4.3.2 Ocular Inclusion Criteria (study eye)
701
a.
Participants must have center-involved macular edema secondary to
702
either CRVO or BRVO. Eyes may be enrolled as early as the time
703
diagnosis of the macular edema, but not longer than 24 months after
704
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diagnosis (by patient history or ophthalmologic diagnosis). The
705
following definitions are used for the purposes of the SCORE Study:
706
i.
A CRVO is defined as an eye that has retinal hemorrhage or other
707
biomicroscopic evidence of retinal vein occlusion (e.g.
708
telangiectatic capillary bed) and a dilated venous system (or
709
previously dilated venous system) in all 4 quadrants.
710
ii.
A BRVO is defined as an eye that has retinal hemorrhage or other
711
biomicroscopic evidence of retinal vein occlusion (e.g.
712
telangiectatic capillary bed) and a dilated venous system (or
713
previously dilated venous system) in 1 quadrant or less of retina
714
drained by the affected vein.
715
iii.
A hemiretinal vein occlusion (HRVO) is defined as an eye that
716
has retinal hemorrhage or other biomicroscopic evidence of retinal
717
vein occlusion (e.g. telangiectatic capillary bed) and a dilated
718
venous system (or previously dilated venous system) in more than
719
1 quadrant but less than all 4 quadrants. Typically, a HRVO is a
720
retinal vein occlusion that involves 2 altitudinal quadrants. For
721
the purposes of the SCORE Study, eyes with HRVO will be treated
722
as eyes with BRVO and analyzed with the BRVO group.
723
b.
ETDRS visual acuity score of greater than or equal to 19 letters
724
(approximately 20/400) and less than or equal to 73 letters
725
(approximately 20/40) by the ETDRS visual acuity protocol.
726
• Note: There will be an enrollment limit of 15% of eyes with visual
727
acuity between 19 and 33 letters. The investigator must believe that
728
a study eye with visual acuity between 19 and 33 letters is perfused.
729
c.
Mean retinal thickness on two OCT measurements greater than or equal
730
to 250 microns (central subfield).
731
d.
Media clarity, pupillary dilation and participant cooperation sufficient
732
for adequate fundus photographs.
733
734
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4.4 Exclusion Criteria
735
4.4.1 General Exclusion Criteria
736
Participants with any of the following conditions are ineligible:
737
a. A condition that, in the opinion of the investigator, would preclude
738
participation in the study (e.g., chronic alcoholism or drug abuse,
739
personality disorder or use of major tranquilizers indicating difficulty in
740
long term follow-up, likelihood of survival of less than 3 years).
741
b. Participation in an investigational trial within 30 days of study entry that
742
involved treatment with any drug that has not received regulatory approval
743
at time of study entry.
744
c. History of allergy to any corticosteroid or component of the delivery
745
vehicle.
746
d. Sitting systolic blood pressure greater than 180 mmHg or diastolic blood
747
pressure greater than 110 mmHg. If the initial reading exceeds these
748
values, a second reading may be taken two or more hours later; the patient
749
may be included (if all other inclusion criteria are met) in the study if the
750
second reading demonstrates a systolic blood pressure equal to or less than
751
180 mmHg and the diastolic blood pressure is 110 mmHg or less. If the
752
blood pressure is brought to 180 mmHg systolic or less and 110 mmHg
753
diastolic or less by antihypertensive treatment, the patient can become
754
eligible.
755
e. The participant will be moving out of the area of the clinical center to an
756
area not covered by another clinical center during the 3 years of the study.
757
f. History of systemic (e.g., oral, IV, IM, epidural, bursal) corticosteroids
758
within 4 months prior to randomization or corticosteroid eyedrops in
759
current use more than 2 times per week.
760
• Note: Patients taking topical, rectal or inhaled corticosteroids are
761
eligible for the study.
762
g. Positive urine pregnancy test: all women of childbearing potential (those
763
who are pre-menopausal and not surgically sterilized) may participate only
764
if they have a negative urine pregnancy test, if they do not intend to
765
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become pregnant during the timeframe of the study and if they agree to use
766
at least one of the following birth control methods: hormonal therapy such
767
as oral, implantable or injectable chemical contraceptives; mechanical
768
therapy such as spermicide in conjunction with a barrier such as a condom
769
or diaphragm; intrauterine device (IUD); or surgical sterilization of
770
partner.
771
772
4.4.2 Ocular Exclusion Criteria (study eye)
773
a. Exam evidence of vitreoretinal interface disease (e.g. vitreomacular
774
traction, epiretinal membrane), either on clinical examination or optical
775
coherence tomography thought to be contributing to macular edema.
776
b. An eye that, in the investigator’s opinion, would not benefit from
777
resolution of macular edema such as eyes with foveal atrophy, dense
778
pigmentary changes or dense subfoveal hard exudates.
779
c. Presence of an ocular condition that, in the opinion of the investigator,
780
might affect macular edema or alter visual acuity during the course of the
781
study (e.g., age-related macular degeneration, uveitis or other ocular
782
inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, prior
783
macula-off rhegmatogenous retinal detachment).
784
d. Presence of a substantial cataract that, in the opinion of the investigator, is
785
likely to be decreasing visual acuity by 3 lines or more (i.e. a 20/40
786
cataract).
787
e. History of laser photocoagulation for macular edema within 4 months
788
prior to randomization.
789
•
Note: If prior grid laser photocoagulation has been performed, the
790
study eye must have either:
791
a.
One or more disc areas of leakage on the fluorescein angiogram
792
(FA). This area of leakage must be contiguous with the fovea
793
and have no evidence of prior laser treatment.
794
OR
795
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b.
Two or more disc areas of leakage on the fluorescein angiogram
796
(FA). This area of leakage must be contiguous with the fovea
797
and have evidence of clearly inadequate prior laser treatment.
798
f. History of intravitreal corticosteroid injection.
799
g. History of peribulbar or retrobulbar corticosteroid use for any reason
800
within 6 months prior to randomization.
801
h. History of panretinal scatter photocoagulation (PRP) or sector laser
802
photocoagulation within four months prior to randomization or anticipated
803
within the next four months following randomization.
804
i. History of pars plana vitrectomy.
805
j. History of major ocular surgery (including cataract extraction, scleral
806
buckle, any intraocular surgery, etc.) within 6 months prior to
807
randomization or anticipated within the next 6 months following
808
randomization.
809
k. History of YAG capsulotomy performed within 2 months prior to
810
randomization.
811
l. IOP greater than or equal to 25 mm Hg.
812
m. Exam evidence of pseudoexfoliation.
813
n. History of steroid-induced IOP elevation that required IOP-lowering
814
treatment.
815
o. History of open angle glaucoma (either primary open angle glaucoma or
816
other cause of open angle glaucoma; note: prior angle closure glaucoma is
817
not an exclusion).
818
• A history of ocular hypertension (or IOP greater than or equal to 22
819
mm Hg without a prior diagnosis of ocular hypertension) is not an
820
exclusion as long as (1) IOP is less than 25 mm Hg, (2) the patient is
821
using no more than one topical glaucoma medication, (3) the most
822
recent visual field, performed within the last 12 months, is normal (if
823
abnormalities are present on the visual field they must be attributable
824
to the patient’s macular disease), and (4) the optic nerve does not
825
appear glaucomatous.
826
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• Note: If IOP is 22 to less than 25 mm Hg, then the above criteria for
827
ocular hypertension eligibility must be met.
828
p. History of herpetic ocular infection.
829
q. History of ocular toxoplasmosis.
830
r. Aphakia.
831
s. Exam evidence of external ocular infection, including conjunctivitis,
832
chalazion or significant blepharitis.
833
t. History of macular detachment.
834
u. Exam evidence of any diabetic retinopathy, defined as eyes of diabetic
835
patients with more than one microaneurysm outside the area of the vein
836
occlusion (inclusive of both eyes).
837
v. History of idiopathic central serous chorioretinopathy.
838
4.4.3 Fellow (Non-Study) Eye Criteria (the Fellow Eye Must Meet the
839
Following)
840
a. ETDRS visual acuity score of greater than or equal to 19 letters
841
(approximately 20/400)
842
b. No prior history of intravitreal corticosteroid injection.
843
c. IOP less than 25 mm Hg.
844
d. No exam evidence of pseudoexfoliation.
845
e. No history of steroid-induced IOP elevation that required IOP lowering
846
treatment.
847
f. No history of open-angle glaucoma (either primary open-angle glaucoma
848
or other cause of open-angle glaucoma; note: angle-closure glaucoma is
849
not an exclusion).
850
• A history of ocular hypertension (or IOP greater than or equal to 22
851
mm Hg without a prior diagnosis of ocular hypertension) is not an
852
exclusion as long as (1) IOP is less than 25 mm Hg, (2) the patient is
853
using no more than one topical glaucoma medication, (3) the most
854
recent visual field, performed within the last 12 months, is normal (if
855
abnormalities are present on the visual field they must be attributable
856
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to the patient’s macular disease), and (4) the optic nerve does not
857
appear glaucomatous.
858
• Note: If the IOP is 22 to less than 25 mm Hg, then the above criteria
859
for ocular hypertension must be met
860
4.5 Informed Consent, Screening Evaluation, and Randomization
861
4.5.1 Informed Consent
862
Potential participants in the SCORE Study will be assessed as part of routine-care
863
examinations. Prior to completing any procedures or collecting any data that are not
864
part of usual medical care, written informed consent will be obtained. The informed
865
consent should be reviewed with the patient at this visit and signed with the
866
understanding that the patient may or may not be eligible. Consent may be given in
867
two stages (if approved by the IRB), with one consent signature obtained prior to
868
screening procedures specific to the SCORE Study that are needed to assess
869
eligibility. The second stage will be obtained prior to randomization and will be for
870
participation in the SCORE Study. Thus, a single consent form will have two
871
signature/date lines for the patient: one for the patient to consent to the screening
872
procedures and one for the patient to consent for the randomized trial. Patients will
873
be encouraged to discuss the SCORE Study with family members and their personal
874
physician(s) before deciding on study participation. Two identical consent forms are
875
signed. One original consent form is to be kept in the participant’s study file and a
876
copy of an original is placed in the participant’s clinical chart. The other original
877
signed consent is for the participant to take home. The informed consent describes
878
the study, randomization procedure, intravitreal steroid treatment and participant
879
responsibilities. Randomization will occur following confirmation of the patient’s
880
eligibility for the study and decision to enter the study.
881
882
4.5.2 Screening Evaluation
883
a. An interview is conducted, including demographic information, medical
884
history including ocular history and current medications. This history is
885
taken in order to ascertain whether there is any medical, ocular, or
886
medication condition that may indicate ineligibility. Participants who are
887
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taking aspirin or warfarin are eligible for the study. However,
888
participants may be requested to refrain from taking warfarin a few days
889
prior to the randomization visit and/or any retreatment visits if they are
890
assigned to receive corticosteroid treatment; this decision is at the
891
discretion of the investigator and the patient’s primary care physician.
892
b. Visual acuity and manifest refraction (done within 8 days prior to
893
randomization). Visual acuity testing and manifest refraction are done
894
using electronic ETDRS (E-ETDRS) visual acuity testing at 3 meters
895
using the Electronic Visual Acuity Tester by a SCORE certified
896
technician. This testing procedure has been validated against 4 meter
897
standard ETDRS chart testing. Given the critical importance of visual
898
acuity in this study, the best-corrected E-ETDRS visual acuity must be
899
obtained in this very careful and standardized manner. Additionally, a
900
“masked” visual acuity examiner with no knowledge of treatment
901
assignments will perform visual acuity testing at the 4-month, 12-month,
902
24-month and 36-month visits. This “masked” examiner will be an
903
individual not involved with the study except for the purpose of performing
904
visual acuity testing. For example, this individual may be a clinic
905
technician or a study coordinator for another clinical trial, but may not be
906
the study coordinator for this trial.
907
c. IOP (done within 21 days prior to randomization). The IOP of both eyes
908
will be measured prior to randomization. IOP will be measured using a
909
sterile Goldmann applanation tonometer (see MOPP for procedure
910
details).
911
d. Ophthalmic examination including dilated ophthalmoscopy (done within
912
21 days prior to randomization). The participant's ocular status is
913
evaluated by a study participating ophthalmologist for conditions that may
914
make the participant ineligible as well as information necessary to
915
complete the study forms. Lens assessment for cataract at the slit lamp
916
will be performed with grading according to a modified Age-Related Eye
917
Disease Study (AREDS) grading system.
918
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e. Fundus photographs, fluorescein angiography and optical coherence
919
tomography (done within 21 days prior to randomization). Good quality
920
stereoscopic color fundus photographs (7 fields of the study eye and 3
921
fields of the fellow eye) and a fluorescein angiogram as well as two optical
922
coherence tomography measurements per eye are required for all
923
participants. The mean of the 2 OCT measurements will be used to assess
924
eligibility. These procedures are described in: University of Wisconsin-
925
Madison Fundus Photograph Reading Center Fluorescein Angiography
926
and Optical Coherence Tomography protocols.
927
f. Blood pressure measurement (done within 21 days prior to
928
randomization).
929
g. For women of childbearing potential: Urine pregnancy test (done within 21
930
days prior to randomization).
931
932
4.5.3 Randomization
933
A secure Internet-based eligibility, enrollment and randomization system is integrated
934
into the SCORE Study. One eye of each participant will be randomly assigned to
935
either treatment with intravitreal triamcinolone acetonide in one of two doses (4 mg
936
or 1 mg) vs. observation (CRVO) or intravitreal triamcinolone acetonide in one of
937
two doses (4 mg or 1 mg) vs. observation/grid laser photocoagulation (BRVO).
938
Treatment assignments, generated by the SCORE Data Coordinating Center, will be
939
stratified according to the following disease groups: CRVO, BRVO without dense
940
macular hemorrhage, and BRVO with dense macular hemorrhage; and baseline visual
941
acuity according to the following categories: good visual acuity (59-73 letters: 20/40
942
to 20/63), moderate visual acuity (49-58 letters: 20/80 to 20/100), and poor visual
943
acuity (19-48 letters: 20/125-20/400). In participants with both eyes eligible and
944
when both eyes have the same disease (CRVO or BRVO), the eye to be randomized
945
into the SCORE Study will be at the discretion of the physician and patient. Only one
946
eye per participant may be randomized into the SCORE study. In participants with
947
both eyes eligible, but where the disease is different (i.e. CRVO in one eye and
948
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BRVO in the other eye) the eye to be randomized into the SCORE Study will also be
949
at the discretion of the physician and patient.
950
951
4.6 Standard Care Groups
952
For study eyes with CRVO, standard care consists of observation of the macular edema.
953
For study eyes of BRVO participants with a dense macular hemorrhage, standard care is
954
observation followed by grid laser photocoagulation if and when clearing of the
955
hemorrhage permits grid laser photocoagulation. For study eyes of BRVO participants
956
without a dense macular hemorrhage at enrollment, standard care consists of immediate
957
grid laser photocoagulation. The determination of a dense hemorrhage in the center of the
958
macula (and thus the timing of the grid laser photocoagulation) is left to the discretion of
959
the investigator. For all three groups, neovascular complications will be treated as
960
necessary.
961
962
The timing of, and criteria for, retreatment with laser photocoagulation are detailed in
963
Section 4.8.3.
964
965
4.6.1 Photocoagulation Procedures
966
Participants with BRVO assigned to standard care who are eligible for laser (i.e., no
967
dense macular hemorrhage) will have laser photocoagulation performed to treat both
968
focal leaks, if any, and areas of diffuse retinal thickening. The investigator has the
969
flexibility to determine the total number of burns required for treatment. However,
970
the total number of burns delivered will depend on the number of focal leaks present,
971
if any, and the area of diffuse retinal thickening present. If the eye is not eligible for
972
laser photocoagulation at the randomization visit because of the presence of dense
973
macular hemorrhage, the participant will be re-evaluated at 4-month intervals. If the
974
macular hemorrhage clears, laser photocoagulation will be performed at that time.
975
The following guidelines should be followed:
976
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Grid Laser Photocoagulation Procedure
977
Size
50-100 um
Exposure
0.05-0.1 seconds
Intensity
Mild
Number
Cover areas of diffuse retinal thickening and treat focal leaks if
any are present
Placement
1-2 burn width apart (500-3000um from center of fovea)
Wavelength
Green to yellow
978
979
4.7 Intravitreal Steroid Groups
980
Study eyes of CRVO and BRVO participants randomized to intravitreal steroid injection(s)
981
will be given triamcinolone acetonide, in a masked fashion, in one of two doses (1 mg or 4
982
mg), depending on the treatment assignment.
983
984
The timing of, and criteria for, retreatment with intravitreal triamcinolone injections are
985
detailed in section 4.8.3.
986
987
4.7.1 Intravitreal Injection of Triamcinolone Acetonide
988
The study drug formulation (triamcinolone acetonide) used in the SCORE Study has
989
been developed by Allergan, Inc. (Irvine, CA). The physical, chemical and
990
pharmaceutical properties of the study drug and formulation are detailed in the
991
Clinical Investigator’s Brochure. Topical antibiotic drops will be administered in the
992
study eye prior to injection (on the day of injection) and for three days post injection.
993
Prior to injection, a standard prep will include povidone iodine and a sterile lid
994
speculum. The same technique is followed for both the initial treatment and for
995
retreatment. The full injection procedure is described in the SCORE Study MOPP.
996
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4.8 Participant Visit Schedule, Retreatment, Alternate Treatment and Other
998
Treatments
999
Note: The SCORE Study protocol under protocol versions 6.0 and earlier specified 3
1000
year follow-up on all study participants. Under Protocol version 7.0 and higher
1001
(February 10, 2008), the last day of enrollment is February 29, 2008 and the last day
1002
of participant follow-up is February 28, 2009 to allow all participants at least one
1003
year of follow-up for primary efficacy assessment. Testing procedures at a study
1004
participant’s final study visit, which will take place at one of the following visits: M12,
1005
M16, M20, M24, M28, M32, or M36, will be performed as described in Section 4.8.2.
1006
Patients who are injected in February 2009 will still need to come in for their Day 4
1007
and Month 1 safety visits, even though these safety visits may be late, i.e. they may
1008
occur after February 28, 2009. (Late safety visits are required to safeguard patient
1009
safety, but, to ensure comparability between groups, late safety visits will not be part
1010
of the trial safety analysis). All study participants active under Protocol Version 7.0
1011
who will not reach their Month 36 visit by February 28, 2009 will be asked to sign an
1012
addendum to the informed consent form.
1013
4.8.1 Visit Schedule
1014
Appendix 1 shows the follow-up visit schedule for all participants through month 36.
1015
Participants in each of the 3 treatment groups will have follow-up visits every 4
1016
months. The visit windows are ± 2 weeks during the first 12 months and ± 8 weeks
1017
after 12 months.
1018
• The visits at 4 months (± 2 weeks), 12 months (± 2 weeks), 24 months (±
1019
8 weeks), and 36 months (± 8 weeks) are designated for outcome
1020
assessment visits. At these visits, certain additional testing is performed
1021
that is not performed at other visits.
1022
• For the visits at 8, 16, 20, 28, and 32-months, the end of the visit window
1023
may be extended if necessary so that the visit occurs no sooner than 3.5
1024
months since the last treatment.
1025
Additional visits may occur as required for usual care of the study participant
1026
• In the intravitreal triamcinolone groups, post-injection safety visits will be
1027
performed at 4 days and 4 weeks after each intravitreal injection.
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• Assessment of ocular symptoms or ocular problems other than for macular
1029
edema or the follow-up of adverse events may require additional visits.
1030
These visits are to be scheduled promptly at the investigator’s discretion.
1031
1032
4.8.2 Testing Procedures to be Performed at Follow-up Visits (see Appendix 1)
1033
The following procedures will be performed at each 4-month follow-up visit on both
1034
eyes unless otherwise specified.
1035
1. E-ETDRS visual acuity. Protocol refraction will be performed at the 4,
1036
12, 24 and 36 month visits. At other visits, the need for a refraction is
1037
determined by the investigator based on usual care considerations. A
1038
refraction should be performed when there is a change in visual acuity of
1039
15 or more letters (better or worse) from the visual acuity score at the time
1040
of the last refraction.
1041
2. IOP measurement using the Goldmann tonometer.
1042
3. Ophthalmic examination, including a dilated fundus examination and a
1043
slit-lamp examination.
1044
4. Fundus photography. Three field fundus photography will be performed on
1045
the study eye at all visits except at 12, 24, and 36 months, at which time
1046
seven field fundus photography will be performed. Three field fundus
1047
photography will be performed on the non-study eye at 12, 24, and 36
1048
months.
1049
5. Optical coherence tomography. To be performed on both eyes at 4, 12, 24,
1050
and 36 months and on the study eye only at other visits.
1051
6. Lens assessment, using modified AREDS standard lens photographs, for
1052
cataract will be performed at 4, 12, 24, and 36 months.
1053
7. Fluorescein angiography will be performed at 4, 12, and 24 months. The
1054
fluorescein angiography protocol directs image capture from both eyes,
1055
with emphasis on the study eye.
1056
8. Blood pressure measurements will be performed at 12, 24, and 36 months.
1057
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Visual acuity, IOP, and an ophthalmic examination will be performed at the 4-
1059
day (+/-3 days) and 4-week (+/-7 days) post-injection safety visits. At
1060
unscheduled visits, the procedures performed will be determined by the
1061
investigator.
1062
4.8.3 Retreatment Assessment
1063
At each 4-month visit during follow-up, the investigator will assess whether persistent
1064
or recurrent macular edema is present that warrants retreatment with the
1065
randomization assigned treatment.
1066
1067
Only those eyes assigned to intravitreal triamcinolone and those eyes eligible for laser
1068
photocoagulation (i.e. eyes with BRVO and without a dense macular hemorrhage) are
1069
eligible for retreatment.
1070
1071
Retreatment, when indicated, will be performed within 4 weeks after the follow-up
1072
visit. Retreatment should not be performed sooner than 3.5 months from the time of
1073
the last treatment.
1074
1075
If retreatment is deferred because the patient has responded well to prior treatment,
1076
then the patient can either be scheduled to be seen in 4 months or can be seen sooner
1077
at investigator’s discretion.
1078
1079
4.8.3.1
Retreatment Criteria
1080
In general, the patient will be retreated with the randomization-assigned
1081
treatment unless there are specific reasons not to retreat, in which case the
1082
investigator may decide to postpone treatment, although postponing treatment
1083
is not required. The reasons for not retreating include:
1084
1085
1. Treatment has been successful and may not need to be repeated if one of
1086
the following is present:
1087
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a. The investigator considers the center of the macula nearly flat. (Note:
1088
for the purposes of this study, as a guideline, the center of the macula
1089
should not be considered flat if the OCT central subfield is greater
1090
than 225 microns).
1091
b. ETDRS visual acuity score of 79 or more letters (approximately 20/25
1092
or better).
1093
c. In the opinion of the investigator, there has been substantial
1094
improvement in macular edema from the last treatment session (e.g., >
1095
50% decrease in retinal thickening [thickening is not retinal thickness;
1096
it is the difference between normal retinal thickness and observed
1097
retinal thickness] in the central subfield) AND further spontaneous
1098
improvement (without additional treatment) in macular edema might
1099
be expected.
1100
1101
2. Additional treatment is contraindicated because either the patient had a
1102
significant adverse effect from prior treatment or maximum treatment has
1103
already been received. Examples include the following:
1104
•
The participant had an IOP elevation after a previous steroid
1105
injection that required treatment to lower the IOP. (Note: an
1106
investigator may choose to retreat a participant who developed
1107
IOP elevation that has been controlled or is currently controlled
1108
with treatment as long as IOP currently is 35 mm Hg or less. If
1109
the IOP is greater than 35 mm Hg, then the IOP must be lowered
1110
before retreatment is given).
1111
•
In the investigator’s judgment, maximum safe laser
1112
photocoagulation has been performed and therefore additional
1113
laser photocoagulation is contraindicated
1114
1115
3. Additional treatment seems "apparently futile":
1116
Additional treatment will be defined as "apparently futile" if 8 or more
1117
months transpire, during which there have been 2 procedures (either laser
1118
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photocoagulation or intravitreal triamcinolone injection, according to the
1119
randomization assigned treatment), and during which there is no evidence
1120
of at least “borderline improvement.”
1121
An eye is considered to have at least "borderline improvement" if it meets
1122
either of the following criteria compared with the findings at the beginning
1123
of the 8 or more months period:
1124
a. An increase in visual acuity score of 5 or more letters.
1125
or
1126
b. A decrease in calculated retinal thickening (measured thickness minus
1127
175 microns in the OCT central subfield of the six-radial scan map)
1128
that is at least 50 microns and represents at least a 20% reduction in
1129
calculated retinal thickening (measured thickness minus 175 microns)
1130
compared with the findings at the beginning of the 8 or more months
1131
period.
1132
If the eye meets the criteria for additional treatment being “apparently futile”, the
1133
treating ophthalmologist may elect to discontinue further treatment at this visit.
1134
However, the treating ophthalmologist is not obligated to discontinue treatment at
1135
this visit and may perform an additional treatment (either laser photocoagulation
1136
or intravitreal triamcinolone injection, according to the randomization assigned
1137
treatment) if desired.
1138
1139
Example of “Apparently Futile” at 20 Months After Study Enrollment
1140
An eye improved in visual acuity from 55 letters (approximately 20/80) to 70
1141
letters (approximately 20/40) and in OCT from 400 to 300 microns during the
1142
first year of follow-up (i.e., at the 12-month follow-up the visual acuity was 70
1143
letters (approximately 20/40) and the OCT measured 300 microns) and had
1144
intravitreal injections at baseline, 6, 12, and 16 months. Between 12 and 20
1145
months the eye never had a visual acuity measured at better than 70 letters
1146
(approximately 20/40) and the smallest OCT thickness measured was 290 (less
1147
than 50 microns reduction from 300 microns measured at 12 months). Because
1148
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there is no evidence of at least “borderline improvement” during these last 8
1149
months, the treating ophthalmologist may wish to discontinue treatment at this
1150
visit. However, continued treatment is not forbidden. If treatment is
1151
discontinued, the investigator may choose to reinstate treatment at a subsequent
1152
visit (such as, if the investigator believes that vision and/or retinal thickening has
1153
worsened).
1154
1155
If the OCT thickness at the beginning of the 8 or more months period had been
1156
500µm, a reduction of at least 65µm would have been required to meet the at
1157
least borderline improvement definition (beginning calculated retinal thickening
1158
500-175 = 325; 20% reduction = 65µm).
1159
1160
Note: This example is for a patient assigned to receive intravitreal triamcinolone
1161
injection. However, this example is also applicable for patients with BRVO and
1162
without a dense macular hemorrhage who have received laser photocoagulation.
1163
1164
4.8.4 Alternate Treatment for the Study Eye
1165
Although it is preferable that study eyes assigned to standard care (i.e., laser
1166
photocoagulation for BRVO eyes without a dense macular hemorrhage or
1167
observation for CRVO eyes or observation for BRVO eyes with a dense macular
1168
hemorrhage) not be treated with intravitreal triamcinolone acetonide and for study
1169
eyes assigned to intravitreal triamcinolone acetonide not be treated with laser
1170
photocoagulation, it is recognized that there may be situations where the
1171
investigator strongly believes that the alternate treatment should be provided.
1172
1173
An eye may be treated with the alternate treatment when it has experienced:
1174
1.
A 15-letter decrease from baseline in best-corrected visual acuity that is
1175
present at two consecutive 4-month interval visits.
1176
AND
1177
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2.
The decrease in visual acuity is due to persistent or recurrent macular edema
1178
(i.e. not due to cataract or other abnormality) that is documented on OCT.
1179
(Note: for the purposes of this study, as a guideline, the center of the macula
1180
should not be considered flat if the OCT central subfield is >225 microns).
1181
1182
When the above criteria are met, an eye assigned to a standard care group may
1183
receive (but is not required to receive) intravitreal triamcinolone (4 mg dose, study
1184
formulation) and BRVO eyes without a dense macular hemorrhage assigned to
1185
intravitreal triamcinolone injection may receive (but are not required to receive)
1186
laser photocoagulation. When the above criteria are met, the investigator should
1187
only provide the alternate treatment if the investigator strongly believes that the
1188
alternate treatment is in the patient’s best interest.
1189
1190
4.8.5 Other Treatments
1191
If, in the investigator’s judgment, the study eye requires additional treatment other
1192
than laser photocoagulation or intravitreal triamcinolone injection, then the Study
1193
Chair or Co-Chair should be contacted to discuss possible treatments. However,
1194
anti-inflammatory topical medication may be prescribed for treatment of the study
1195
eye without Study Chair or Co-Chair consultation.
1196
1197
4.9 Diagnosis and Treatment of Adverse Events
1198
4.9.1 Endophthalmitis Treatment
1199
The decision to treat a patient for an endophthalmitis or a suspected endophthalmitis
1200
will be guided by the clinical judgment of the investigator. The treatment method
1201
(pars plana vitrectomy vs. vitreous tap) and choice of antimicrobial agents is also at
1202
the discretion of the investigator and should follow current standard practice patterns.
1203
The decision to use intravitreal steroids (e.g. dexamethasone) for the treatment of
1204
endophthalmitis is also at the discretion of the investigator.
1205
1206
4.9.2 Treatment of Elevated Intraocular Pressure (IOP)
1207
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It is expected that some patients will have an IOP rise that may require treatment to
1208
lower the IOP.
1209
1210
Treatment of elevated IOP will be instituted whenever the IOP is greater than or equal
1211
to 30 mm Hg. The treatment to prescribe will be at investigator discretion and may
1212
include referral to another ophthalmologist. If the IOP is between 22 and 30 mm Hg,
1213
then the IOP should be measured again within one month and treated if greater than or
1214
equal to 30 mm Hg. IOP greater than 25 mm Hg at consecutive 4-month visits should
1215
be treated. If IOP is greater than 25 mm Hg for 4 months, then a visual field should
1216
be performed to evaluate for glaucomatous damage.
1217
1218
The treatment to prescribe is at the discretion of the investigator and may include
1219
referral to another ophthalmologist. One treatment regimen that can be followed was
1220
used in the Collaborative Initial Glaucoma Treatment Study53 and is listed below:
1221
1222
Participants may receive a sequence of medications, which may begin with a topical
1223
beta-blocker, followed by an alternate single topical therapeutic agent, dual topical
1224
therapy, triple topical therapy, an alternate combination of triple topical therapy, and
1225
an optional additional topical and/or oral medication or medications. If further
1226
treatment is required, the next treatment step may be argon laser trabeculoplasty,
1227
followed by trabeculectomy, medication, trabeculectomy with an antifibrotic agent,
1228
and medication.
1229
1230
4.9.3 Cataract Surgery
1231
It is expected that some study participants in both the intravitreal steroid arms and the
1232
standard care arms will develop cataract within the study period. The decision to
1233
perform cataract surgery is at the discretion of the investigator and the patient.
1234
Indications for cataract surgery should follow guidelines developed by the American
1235
Academy of Ophthalmology, Preferred Practice Pattern (Cataract in the Adult Eye,
1236
Anterior Segment Panel, 2001, page 15). Similar guidelines have been adopted by the
1237
Department of Health and Human Services (Medicare Program; Limitations on
1238
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Medicare Coverage of Cataract Surgery, October 6, 1995):
1239
Indications for Cataract Surgery:
1240
1. Visual function that no longer meets the participant’s needs and for which
1241
cataract surgery provides a reasonable likelihood of improvement.
1242
2. Lens opacity that inhibits optimal management of posterior segment disease.
1243
3. The lens causes inflammation (phakolysis, phakoanaphylaxis), angle
1244
closure, or medically unmanageable open-angle glaucoma.
1245
1246
Participants in both the intravitreal steroid groups and the standard care groups
1247
should be assessed for the development of cataract in a similar fashion. Cataract
1248
surgery may be performed at any time that this is indicated clinically.
1249
1250
4.9.4 Surgery for Proliferative Retinopathy and Other Complications Due to
1251
Retinal Vein Occlusion
1252
It is expected that some study participants will develop vitreous hemorrhage and/or
1253
other complications of retinal vein occlusion that may cause visual impairment.
1254
Vitrectomy for the complications of proliferative retinopathy such as vitreous
1255
hemorrhage should be delayed, if clinically feasible, because vitreous hemorrhage
1256
may resolve, obviating the need for vitrectomy. Furthermore, vitrectomy is thought to
1257
reduce the half-life of intravitreal steroids such that participants assigned to the
1258
steroid treatment arms may experience reduced benefit from intravitreal steroid
1259
injections following vitrectomy.
1260
1261
A suggested treatment plan that may be followed for eyes with vitreous hemorrhage
1262
and/or other complications of retinal vein occlusion is as follows:
1263
1. Eyes with visually significant, non-clearing vitreous hemorrhage should
1264
have vitrectomy performed if there is no significant clearing in 3 months.
1265
2. Eyes with traction retinal detachment involving or threatening the fovea
1266
should have vitrectomy performed as soon as clinically indicated.
1267
3. Eyes with a combined traction-rhegmatogenous retinal detachment should
1268
have vitrectomy performed as soon as clinically indicated.
1269
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4. Eyes with extensive and progressive fibrovascular proliferation should have
1270
vitrectomy performed as soon as clinically indicated.
1271
5. Eyes with vitreoretinal interface disease such as from vitreomacular traction
1272
or an epiretinal membrane can, at the discretion of the investigator, have
1273
vitrectomy performed if the investigator believes that the primary cause of
1274
macular edema and reduced visual acuity is due to the vitreoretinal interface
1275
disease.
1276
1277
4.10
Miscellaneous Treatments During Follow-up
1278
4.10.1 Treatment of Macular Edema in Non-study Eye
1279
If a non-study eye that was not eligible for enrollment develops macular edema
1280
associated with retinal vein occlusion requiring treatment, the treatment will depend
1281
on the randomization group of the study eye. The following also applies to the non-
1282
study eye of a patient who presents with both eyes eligible for the SCORE study at
1283
screening and when both eyes have the same disease (CRVO or BRVO) or if each eye
1284
has a different disease (i.e. one eye has a CRVO and the other eye has a BRVO).
1285
•
If the study eye was assigned to an intravitreal corticosteroid group, then
1286
the non-study eye will receive standard care to avoid treating both eyes
1287
with intravitreal corticosteroids.
1288
•
If the study eye was assigned to standard care, then the non-study eye may
1289
be treated with either intravitreal corticosteroids (study preparation, 4 mg
1290
dose only) or standard care at investigator/patient discretion. A non-study
1291
eye treated with the study steroid preparation will undergo the same follow-
1292
up schedule, retreatment regimen and adverse event monitoring as study
1293
eyes in the SCORE Study.
1294
1295
4.10.2 Panretinal Photocoagulation (PRP) Treatment:
1296
PRP or sector PRP can be given if it is indicated in the judgment of the investigator
1297
and following guidelines established by the CVOS and BVOS. Recall that
1298
participants are not eligible for the SCORE Study if, at the time of randomization, it
1299
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is expected that they will need PRP within 4 months. The following guidelines
1300
should be followed:
1301
Burn Characteristics
1302
1303
Size (on retina)
500 microns
Exposure
0.1 seconds recommended, 0.05 to 0.2 allowed
Intensity
mild white
Distribution
edges 1 burn width apart
No. of Sessions/Sittings
unrestricted (each session generally should be completed in <6 sittings)
Nasal proximity to disk
No closer than 500 microns
Temp. proximity to center
No closer than 3000 microns
Superior/inferior limit
No further posterior than 1 burn within the temporal arcades
Wavelength
Green to yellow (red can be used if vitreous hemorrhage is present
precluding use of green or yellow)
1304
5.
Data Monitoring and Adverse Event Reporting
1305
5.1 Data Safety Monitoring Committee
1306
The SCORE Data and Safety Monitoring Committee (DSMC) is responsible for reviewing
1307
the study design and, as appropriate, recommending design changes to the SCORE
1308
Executive Committee and the NEI. The DSMC also may recommend to the NEI to
1309
suspend enrollment if adverse events predominate. In addition, the DSMC assesses study
1310
data, particularly for adverse and/or beneficial effects of treatment. The DSMC is expected
1311
to meet at least every six months and will review all accumulating study data including
1312
adverse events. The SCORE Data Coordinating Center (DCC) will report to the DSMC
1313
expeditiously, on a case-by-case basis, specific adverse events described in the DSMC
1314
Standard Operating Procedure document. In addition, the DSMC will review early safety
1315
data on patients from the SCORE Study and from the Diabetic Retinopathy Clinical
1316
Research Network (DRCR.net) study on intravitreal triamcinolone and diabetic macular
1317
edema. Both studies are served by the same DSMC and both studies will use the same drug
1318
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formulation. The SCORE Study will not proceed if there are any serious concerns
1319
identified with the formulation or the injection procedure. The monitoring plan that the
1320
DSMC will follow is:
1321
• An initial report will include the day 4 follow-up data from the first 5 patients
1322
(combined in the DRCRnet and SCORE studies) who receive an intravitreal
1323
triamcinolone injection. No additional patients will receive an intravitreal
1324
injection until these data have been obtained and it is clear that there are no
1325
immediate safety concerns.
1326
• A second report will be compiled after 5 patients have completed the 4-week post
1327
injection exam. It will include the 4-day data on a second group of 5 patients.
1328
Note: no more than 10 patients will receive intravitreal injections until the first 5
1329
patients have completed at least 4 weeks of follow up. Thereafter, assuming that
1330
there have not been any unexpected consequences of the injections, enrollment
1331
will be opened to all sites.
1332
• A third report will be compiled after 10 patients who receive an intravitreal
1333
triamcinolone injection have completed the 4-week post injection exam.
1334
Thereafter, assuming that there have been no safety concerns, the data will be reviewed
1335
on a monthly basis by the DSMC until the committee is comfortable with reviewing the
1336
data on a less frequent schedule.
1337
1338
5.2 Methods and Timing for Assessing, Recording and Analyzing Safety Parameters
1339
Each clinical site is responsible for reporting all adverse events, including toxicities, that
1340
occur to SCORE participants enrolled at their site, regardless of relatedness to study
1341
therapy or procedure. Reporting of all adverse event data is expected upon recognition.
1342
1343
Serious adverse events (SAEs), as defined in Section 5.3.1.2 must be reported to the
1344
SCORE DCC within 24 hours of recognition. Study investigators must report serious
1345
adverse events to their local ethics review committee (or IRB) promptly in accordance with
1346
local regulations or policies in addition to the SCORE DCC. The SCORE DCC may
1347
request additional information regarding adverse events from investigators following their
1348
initial review.
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1350
5.3 Procedures for Reporting Adverse Events
1351
Clinical sites are required to report all adverse events via the SCORE electronic data
1352
capture system (AdvantageEDCSM). Each site will receive training on reporting
1353
requirements. Electronic forms that are designed to collect adverse event data will be
1354
available for input at any time, including between scheduled visits.
1355
1356
When a reported adverse event is determined to be serious, unexpected, and to have a
1357
reasonable possibility to be related to the test product or procedure, or otherwise reportable
1358
to regulatory agencies or drug manufacturers, the SCORE DCC will prepare an initial
1359
report as described below. Cumulative reports of other adverse events not considered
1360
serious will also be prepared by the SCORE DCC and reviewed by the Medical Monitor on
1361
at least a monthly basis, and by the DSMC on a routine basis at least semi-annually.
1362
1363
5.3.1 Routine SCORE DCC Review
1364
The SCORE DCC Medical Monitor will be provided relevant material in order to
1365
assess whether there are safety concerns that may require expedited reporting to the
1366
FDA, DSMC, local ethics committee (or IRB), study investigators, the pharmaceutical
1367
manufacturer, or the study sponsor (National Eye Institute). A report of new adverse
1368
events will be reviewed each weekday by the SCORE DCC. Other data are reviewed
1369
weekly by the SCORE DCC.
1370
1371
5.3.1.1 Definition of Adverse Event
1372
An adverse event (AE) is defined as any untoward medical occurrence in a
1373
patient or clinical investigation subject administered a pharmaceutical product
1374
and that does not necessarily have a causal relationship with this treatment. An
1375
adverse event can therefore be any unfavorable and unintended sign (including
1376
an abnormal laboratory finding), symptom, or disease temporally associated
1377
with the use of a medicinal (investigational) product, whether or not related to
1378
the medicinal (investigational) product.
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• Unexpected Adverse Drug Reaction – An adverse reaction, the nature or
1380
severity of which is not consistent with the applicable product
1381
information (e.g. Investigator’s Brochure for an unapproved
1382
investigational product or package insert / summary of product
1383
characteristics for an approved product.).
1384
1385
Throughout the study, all adverse events must be recorded in the
1386
AdvantageEDC, regardless of the severity or relationship to study medication or
1387
procedure. If an adverse event is caused by a combination of treatment and
1388
disease, the adverse event should be graded as it is observed. Early in the
1389
development of a therapy, when little is known about the therapy’s safety
1390
profile, it is especially important to maintain a high level of suspicion and report
1391
adverse events that may be treatment-related adverse events. This reporting may
1392
facilitate identification of idiosyncratic or low frequency treatment-related
1393
adverse events.
1394
1395
5.3.1.2 Serious Adverse Event (SAE)
1396
A serious adverse event (SAE) is defined as any adverse event occurring at
1397
any dose that results in any of the following outcomes:
1398
a. Death;
1399
b. Life-threatening adverse event*;
1400
c. In-patient hospitalization or prolongation of existing hospitalization;
1401
d. Persistent or significant disability / incapacity;
1402
e. Congenital anomaly / birth defect.
1403
* Including any adverse drug experience that places the patient or subject,
1404
in the view of the investigator, at immediate risk of death from the reaction
1405
as it occurred (i.e., it does not include a reaction that, had it occurred in a
1406
more severe form, might have caused death).
1407
1408
Important medical events that may not result in death, be life-threatening, or
1409
require hospitalization may be considered a serious adverse event when,
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based upon appropriate medical judgment, they may jeopardize the patient
1411
or subject and may require medical or surgical intervention to prevent one of
1412
the outcomes listed in this definition.
1413
1414
5.3.1.3 Expected and Unexpected Adverse Event
1415
All adverse events, be they routine or serious, will be classified as either
1416
expected or unexpected. Any adverse therapeutic experience that is associated
1417
with the study therapy or procedure and is listed as such in an investigational
1418
plan, investigational brochure, protocol or informed consent is an expected
1419
event. In contrast, any adverse therapeutic experience, the specificity or severity
1420
of which is not consistent with the investigational plan, investigator brochure,
1421
protocol, or informed consent for the therapy is an unexpected event.
1422
1423
5.3.2 Adverse Event Severity Grading
1424
Severity grades are assigned by the study site to indicate the severity of all adverse
1425
experiences. The SCORE Study has adapted usage of The National Cancer Institute's
1426
Common Terminology Criteria for Adverse Events (CTCAE) for application in adverse
1427
event reporting. A copy of the CTCAE system can be found on the SCORE website:
1428
(http://www.emmes.com/).
1429
1430
The CTCAE provides a term and a grade that closely describes the adverse event.
1431
The CTCAE grade for each adverse event should be associated with a severity
1432
category: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-
1433
threatening) and Grade 5 (Death). If the adverse event is not included in the CTCAE,
1434
the following general definitions should be used in determining severity:
1435
1436
Grade 1 Mild
Transient or mild discomforts (<48 hours), no or minimal
1437
medical intervention/therapy required, hospitalization not
1438
necessary (nonprescription or single-use prescription
1439
therapy may be employed to relieve symptoms, e.g.,
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aspirin for simple headache, acetaminophen for post-
1441
surgical pain). Mild adverse effects are an expected
1442
consequence of the SCORE protocol used here, and
1443
standard supportive therapies (per institutional guidelines)
1444
are permitted.
1445
Grade 2 Moderate
Mild to moderate limitation in activity, some assistance
1446
may be needed; no or minimal intervention/therapy
1447
required, hospitalization possible.
1448
Grade 3 Severe
Marked limitation in activity, some assistance usually
1449
required; medical intervention/therapy required,
1450
hospitalization possible.
1451
Grade 4 Life-threatening Extreme limitation in activity, significant assistance
1452
required; significant medical/therapy intervention
1453
required, hospitalization or hospice care probable.
1454
Grade 5 Death
Death.
1455
1456
5.3.3 Relation to Therapy
1457
The physician acting as the Principal Investigator at each study site or his/her
1458
physician designee should make the determination of therapy-relatedness of an
1459
adverse experience. A therapy-related determination must be made for every adverse
1460
event, regardless of severity or event type (routine AE or SAE). A causal relationship
1461
is present if a determination is made that there is a reasonable possibility that the
1462
adverse event may have been caused by the study drug.
1463
1464
5.3.4 Adverse Event Reporting Requirements and Procedures for Clinical Sites
1465
to the SCORE Coordinating Center
1466
All adverse events, deaths, infections, and hospitalizations, regardless of severity,
1467
expectedness, or potential association with the investigational drug, will be entered on
1468
the appropriate form in the AdvantageEDC.
1469
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5.3.4.1 Requirements
1471
Clinical sites are required to enter all known adverse event data from all
1472
events into the electronic adverse event form in the AdvantageEDC.
1473
1474
Serious adverse events are required to be entered into the AdvantageEDC
1475
within 24 hours of recognition. If all information required on the event form
1476
has not been obtained, the site should submit what is available. Additional
1477
information, as it becomes available, can be submitted at a later date.
1478
1479
5.3.5 Reporting Procedures
1480
For reporting of AEs and SAEs, the Site Coordinator will:
1481
1. Complete an Adverse Event form (page 1) in the SCORE data entry
1482
system.
1483
2. If the site determines that the event is serious, the site will complete, in
1484
detail, the Adverse Event Summary (page 2 of the Adverse Event Form).
1485
3. The SCORE Medical Monitor will review the Adverse Event Summary
1486
and complete an Adverse Event Review form (page 3 of the Adverse
1487
Event form).
1488
4. If follow-up information is required, the SCORE DCC will contact the
1489
site.
1490
5. If rapid reporting is required, the SCORE DCC will prepare a MedWatch
1491
and forward copies of the completed MedWatch to the SCORE Study
1492
Chair and Co-Chair, DSMC Chair, and IND sponsor who will send the
1493
MedWatch to the FDA.
1494
1495
5.3.6 SCORE Adverse Event Reporting Contact
1496
The SCORE Project Director (listed in the Data Management Handbook as well as
1497
the current MOPP) may be contacted at the SCORE DCC, The EMMES Corporation,
1498
located in Rockville, Maryland. Be sure to clearly indicate the protocol number and
1499
the location of your site when contacting the SCORE DCC. Back-up personnel and
1500
procedures are in place to assure that if the Project Director is not available, other
1501
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personnel at the SCORE DCC can adequately handle requests or adverse event
1502
reporting requirements. For urgent AE requests that occur after business hours (8:30
1503
– 5:00 Eastern Time), contact:
1504
Maria Figueroa, MBA, CCRP
1505
SCORE Project Director
1506
The EMMES Corporation
1507
Tel. (240) 344-1935
1508
1509
5.4 Procedure for Reporting of Pregnancy
1510
At the time a site Principal Investigator or Study Coordinator becomes aware that a study
1511
participant has become pregnant during the study, the Principal Investigator or Study
1512
Coordinator will prepare a report on the pregnancy to be sent to the SCORE DCC that
1513
includes the following elements:
1514
• Participant (mother’s) coded study identifier(s);
1515
• Date of last menstrual period;
1516
• Date of enrollment;
1517
• Date(s) of fluorescein angiogram(s); and
1518
• Date of last intravitreal injection or laser treatment, if any.
1519
1520
Any pregnancy that occurs during the study should be followed until the time of delivery,
1521
miscarriage or abortion. A report with any relevant information on the condition of the
1522
fetus or infant at birth should be forwarded to the SCORE DCC, including:
1523
• Mother’s coded study identifier(s);
1524
• Gestational age at delivery, miscarriage, or abortion;
1525
• Birth weight, gender, length, and head circumference, if available;
1526
• Apgar scores recorded after birth, if available;
1527
• Any abnormalities. Report all abnormalities as a serious adverse event.
1528
1529
6.
Statistical Considerations
1530
6.1
Scientific and Regulatory Objectives
1531
The SCORE Study’s scientific and regulatory objectives are to compare the efficacy and
1532
safety of standard care with intravitreal injection(s) of triamcinolone acetonide (4 mg or 1
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mg) to treat macular edema associated with CRVO and BRVO. Although scientific goals
1534
parallel regulatory goals, regulatory requirements demand some divergence of scientific
1535
statistical methods from regulatory statistical methods for testing the null hypothesis of no
1536
treatment effect of triamcinolone acetonide. Section 6.2 describes the formal test to be
1537
performed for drug registration, while the remaining sections describe the scientific
1538
statistical approach. The DSMC will be responsible for monitoring the SCORE Study
1539
following the scientific plan only.
1540
1541
6.2
Formal Regulatory Statistical Test of Efficacy
1542
For regulatory purposes, the SCORE Study will be configured as two separate and
1543
independent clinical trials “A” and “B”, each trial to serve as confirmatory of the other. To
1544
accomplish this, clinical sites will be allocated before recruitment commences to either trial
1545
“A” or trial “B”, using a method that strives for comparable geographic patterns and
1546
distributions of enrollees per center. Within each trial, CRVO and BRVO disease areas
1547
will be pooled for analysis and three primary efficacy analyses performed after no more
1548
than one year of follow-up. A detailed description of the method of assigning sites to Trial
1549
“A” and Trial “B” is provided in the SCORE Study Manual of Procedures and Policies
1550
(MOPP). The assignment of sites to Trial “A” and Trial “B” will be made prior to
1551
recruitment of subjects. One analysis will compare 1 mg steroid versus standard care, one
1552
will compare 4 mg steroid versus standard care, and one will compare 1 mg versus 4 mg
1553
steroid. The comparison will be with respect to the primary outcome measure. The
1554
primary outcome measure indicates whether or not a study eye of a participant experiences
1555
an improvement of 15 or more letters from baseline in best-corrected ETDRS visual acuity
1556
score. The significance of the three comparisons will be obtained by Hochberg’s
1557
sequentially rejective procedure, as described in detail in the MOPP, section 6.2. The
1558
overall alpha for the A trial will be no more than 0.05, and similarly for the independent B
1559
trial (more specifically, the alpha for each of the “A” and “B” trials will be diminished from
1560
0.05 by the amount of alpha previously spent on interim scientific efficacy assessments).
1561
Within trial “A” and within trial “B”, an initial analysis of treatment effect will be carried
1562
out by logistic regression to determine whether a statistical interaction exists between
1563
disease group (BRVO and CRVO) and treatment group (standard care, 4 mg steroid, and 1
1564
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mg steroid). A finding of no interaction effect will provide justification for pooling the
1565
CRVO and BRVO participants within trial “A” and trial “B” and the primary efficacy
1566
analyses for regulatory purposes, as described above, will be carried out by means of
1567
logistic regression adjusting for disease area, baseline visual acuity, and center. A
1568
statistically significant interaction effect will require separate primary efficacy analyses for
1569
CRVO and for BRVO within trial “A” and with trial “B”.
1570
1571
6.3 Scientific Statistical Approach
1572
6.3.1
Two Independent Clinical Trials
1573
The SCORE Study consists of two separate independent clinical trials - one for
1574
CRVO and one for BRVO. Each of these clinical trials has its own overall Type I
1575
error (alpha) = .05.
1576
1577
6.3.2
Three Primary Questions in Each Clinical Trial
1578
Each of these clinical trials asks three questions. One question is the comparison of
1579
standard care to 4 mg intravitreal injection(s) of triamcinolone acetonide. A second
1580
question is the comparison of standard care to 1 mg intravitreal injection(s) of
1581
triamcinolone acetonide. The third question compares 1 mg to 4 mg intravitreal
1582
injections. Within each clinical trial, the significance of the comparisons will be
1583
obtained by Hochberg’s sequentially rejective procedure using an alpha level of 0.05
1584
(see the MOPP, section 6.4).
1585
6.3.3
Primary Efficacy Outcome Measure and Time Point
1586
Improvement by 15 or more letters from the randomization visit visual acuity to the
1587
12-month follow-up visual acuity is the primary efficacy outcome measure. Visual
1588
acuity is to be measured using E-ETDRS visual acuity testing.
1589
1590
6.3.3.1
Primary Efficacy Analysis Method
1591
The three treatment comparisons (1 mg versus standard care, 4 mg versus
1592
standard care, and 1 mg versus 4 mg) will be made by means of logistic
1593
regression adjusting for baseline visual acuity, clinical site, and presence of
1594
baseline macular hemorrhage in participants with BRVO. The test statistic
1595
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will be compared to the critical value of the efficacy monitoring guideline
1596
(section 6.7.2). Family-wise error will be controlled at no more than 0.05 by
1597
Hochberg’s sequentially rejective method, modified for interim monitoring as
1598
specified in the MOPP.
1599
1600
The analysis will be on the basis of intent to treat (ITT), treating missing
1601
observations as missing completely at random [i.e., missing data from study
1602
participants will be dropped from the analysis and noncompliance (or
1603
treatment crossover) ignored].
1604
1605
6.3.3.2
Additional Analysis Methods for Consistency of Primary
1606
Efficacy Result
1607
We will investigate two other ITT variants: (1) last-observation-carried-
1608
forward (LOCF) and (2) performing a sensitivity analysis in which outcomes
1609
will be assigned to missing eyes so as to explore both the minimum and
1610
maximum possible estimates of treatment effects. A per-protocol analysis,
1611
excluded from which will be those study participants who drop out, cross over
1612
to another treatment group, or violate the protocol, also will be conducted
1613
including only study eyes that have completed 12-month visual acuity data.
1614
Logistic regression analysis will be performed to adjust for any potential
1615
imbalances in baseline characteristics observed between treatment groups,
1616
with the odds ratio used as a measure of increased or decreased risk.
1617
Important baseline differences, not necessarily based on tests of statistical
1618
significance, will be investigated as to their ability to confound the association
1619
between the treatment groups and the primary outcome. Although the intent-
1620
to-treat analysis described in section 6.3.3.1 is considered to be the definitive
1621
analysis, these additional analyses (e.g. other ITT variants, per-protocol) will
1622
be used to explore the consistency of the result and provide more information
1623
as to the benefit or lack of benefit of the treatment.
1624
1625
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6.4 Assumptions for and Result of Sample Size Estimation
1626
6.4.1 Study Power
1627
The study power is set for each trial at 80%.
1628
1629
6.4.2 Estimate of CRVO Primary Efficacy Outcome in the Standard Care Group
1630
The Central Vein Occlusion Study (CVOS) demonstrated that in participants with
1631
macular edema for more than 3 months secondary to a CRVO, macular grid laser
1632
photocoagulation, as compared to no treatment, did not improve visual acuity.4 There
1633
were no significant differences between treated and untreated participants in either
1634
level of visual acuity or change in visual acuity across all follow-up visits. The data
1635
from the CVOS demonstrate that at 2 years from baseline 18% of treated eyes (10 of
1636
57 eyes) and 11% of untreated eyes (6 of 53 eyes) experienced a gain of three or more
1637
lines of visual acuity. At 1 year, approximately 6% in both the treated and untreated
1638
eyes showed a gain of three or more lines of visual acuity. From these data, it is
1639
conservatively estimated that approximately 15% of untreated eyes with CRVO will
1640
experience a gain of three or more lines of visual acuity at 1 year.
1641
1642
6.4.3 Estimate of BRVO Primary Efficacy Outcome in the Standard Care Group
1643
In the Branch Vein Occlusion Study (BVOS), macular grid laser photocoagulation
1644
was demonstrated to be effective in improving visual acuity in some eyes with BRVO
1645
complicated by macular edema.1 Treatment resulted in a two or more line
1646
improvement in visual acuity for two or more consecutive visits in approximately
1647
45% of eyes at the 2-year follow-up. At one year, approximately 20% of treated eyes
1648
gained two or more lines of visual acuity at two or more consecutive visits. Patients
1649
in the BVOS all had absence of dense macular hemorrhage before enrollment. In the
1650
SCORE Study, we anticipate as many as 50% of participants may have a dense
1651
macular hemorrhage at enrollment and therefore will have grid laser treatment
1652
postponed until the hemorrhage clears to permit treatment. It is uncertain how the
1653
inclusion of these eyes will affect efficacy in the standard care arm of the SCORE
1654
study. From these data, it is conservatively estimated that approximately 35% of
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standard care eyes will experience a gain of three or more lines of visual acuity at 1
1656
year.
1657
1658
6.4.4 Background Information on Efficacy of Intravitreal Injection(s) of
1659
Triamcinolone Acetonide
1660
In Table 4, we provide outcomes of treatment with intravitreal steroid injections
1661
based on six published reports of case series. Data concerning diabetic macular
1662
edema (DME) are included because of the similarity (VEGF related vascular
1663
permeability) between DME and macular edema due to retinal vein occlusion.
1664
Table 4
1665
# of
eyes
treated
Disease
Dose
(mg)
Anatomical
improvement
Mean baseline
visual acuity
Mean visual
acuity at
endpoint
Follow-
up
(mos)
Martidis33
16
DME
4
11/16 (69%)
20/200
20/80
3
Jonas41
26
DME
25
21/21 (FA)
20/160
20/100
6.6
Jonas37
2
CRVO
25
2/2 (100%)
20/160
20/125
3
Greenberg35
2
CRVO
4
2/2 (100%)
20/400
20/160
4.5
Ip36
2
CRVO
4
1/2 (50%)
20/200
20/100
6
Park38
10
CRVO
4
10/10 (100%)
20/80
20/32
4.8
1666
Except for Park et al,38 the six case series above did not use standardized methods to
1667
measure visual acuity. However, all six studies indicate a high likelihood of
1668
significant visual acuity improvement for treatment of macular edema with
1669
intravitreal triamcinolone acetonide. The report by Martidis33 showed 11 of 16
1670
DME eyes (69%) having a 3-line improvement in visual acuity at the last follow-up
1671
visit for each eye, which was either 3 or 6 months after the intravitreal injection.
1672
Park et al38 showed that 7/10 (70%) had a 3 or more line improvement after a mean
1673
of 4.8 months follow up. Further, unpublished data (Martidis et al and Ip et al),
1674
some of which were presented at the 2002 Retina Congress (San Francisco, CA),
1675
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provide additional evidence of the efficacy of this treatment for macular edema
1676
secondary to retinal vein occlusion and diabetic macular edema. Martidis et al, at
1677
the 2002 Retina Congress, reported additional information on efficacy for DME:
1678
73/125 (58%) had a two or more Snellen line improvement at an average follow-up
1679
of 6.7-months. For BRVO with prior laser treatment, 6/13 (46%) had a three or
1680
more Snellen line improvement at 6 months. Ip et al, at the 2002 Retina Congress,
1681
reported additional information on efficacy for CRVO (three Snellen line
1682
improvement): 3/8 (38%) had a three or more Snellen line improvement at 6
1683
months.
1684
1685
6.4.4.1
Estimate for CRVO Primary Efficacy Outcome in the
1686
Intravitreal Injection(s) Groups
1687
For CRVO eyes, our projected rate of improvement of 15 or more letters at
1688
one year is 30% in the 1 mg and in the 4 mg injection group.
1689
1690
6.4.4.2
Estimate for BRVO Primary Efficacy Outcome in the
1691
Intravitreal Injection(s) Groups
1692
For BRVO eyes in the SCORE Study, in which all eyes will not have had prior
1693
laser treatment, we expect efficacy for eyes receiving intravitreal injection(s)
1694
of triamcinolone to be higher, and project 53% will have an improvement of
1695
15 or more letters at 1 year in the 1 mg and in the 4 mg group.
1696
6.4.5 Sample Size Estimate
1697
The sample size estimate (number per group) was computed assuming the efficacy in
1698
the two steroid doses are the same. If the efficacy in the 4 mg group is higher than the
1699
1 mg group, and given the other preceding assumptions, the study power will be
1700
higher for the standard care versus 4 mg comparison. This was considered important
1701
because the 4 mg dose is the basis for all available information.
1702
1703
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Sample Size Estimate
1704
Type I error (alpha) = .025, study power = 80%
1705
CRVO
BRVO
1706
Standard care
15%
35%
1707
1 mg or 4 mg
30%
53%
1708
N per group
147
147
1709
The allocation ratio will be 1:1:1 for standard care: 1 mg: 4 mg. The number per
1710
group has been increased by 10% to allow for some missing data at 12 months
1711
(number per group=162). Thus, the total sample estimate for the CRVO trial is 486
1712
(3 times 162) and for the BRVO trial the total sample estimate is 486 (3 times 162).
1713
1714
6.5 Safety Outcomes
1715
Safety outcomes that will be assessed include serious adverse events and specific ocular
1716
events requested by the Data and Safety Monitoring Committee. The SCORE Study DCC
1717
and DSMC will continuously monitor the following safety indicator variables:
1718
• Cataract
1719
• IOP exceeding 35 while on maximal medical therapy
1720
• Filtration surgery to lower IOP
1721
• Non-infectious endophthalmitis
1722
• Any of: infectious endophthalmitis, retinal detachment, vitreous hemorrhage, loss of
1723
20 ETDRS letters at 4 days or 4 week post injection, a new-onset retinal arterial
1724
occlusion, a transition from a branch to a central retinal vein occlusion, a new,
1725
clearly independent branch retinal vein occlusion, or anterior ischemic optic
1726
neuropathy.
1727
Table 5 indicates the precision with which the SCORE Study will be able to estimate rates
1728
of safety events at the end of the trial. Three sample sizes are provided in Table 5:
1729
• N=162: within each study arm.
1730
• N=324: pooling the 1 mg and 4 mg intravitreal injection arms within CRVO or
1731
BRVO disease area OR pooling the 1 mg or 4 mg intravitreal injection arm across
1732
each disease area.
1733
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• N=648: pooling the 1 mg and 4 mg intravitreal injection arms across each disease
1734
area.
1735
For example, if the true rate is 0.25 and the sample size is 162, the 10% quantile for the
1736
lower 95% confidence limits is 0.15, and the 90% quantile for the upper 95% confidence
1737
limit and half-width are 0.36 and 0.07, respectively.
1738
1739
Table 5: 90% limits for 95% confidence intervals of rates of safety events,
1740
as a function of the true rate p and the sample size N
1741
1742
N=162
N=324
N=648
P
Lower
CL
Upper
CL
Half
width
Lower
CL
Upper
CL
Half-
width
Lower
CL
Upper
CL
Half-
width
0.01
0.00
0.05
0.02
0.00
0.04
0.02
0.00
0.03
0.01
0.03
0.00
0.09
0.04
0.01
0.07
0.02
0.01
0.06
0.02
0.05
0.01
0.13
0.04
0.02
0.10
0.03
0.03
0.08
0.02
0.1
0.03
0.19
0.05
0.05
0.16
0.04
0.06
0.14
0.03
0.15
0.07
0.25
0.06
0.09
0.22
0.04
0.11
0.20
0.03
0.25
0.15
0.37
0.07
0.18
0.33
0.05
0.20
0.31
0.03
0.5
0.37
0.63
0.08
0.41
0.59
0.06
0.44
0.57
0.04
1743
6.6 Secondary Efficacy Outcomes
1744
Secondary efficacy outcomes will be analyzed by comparing each triamcinolone group (4
1745
mg or 1 mg) to standard care as well as by comparing 4 mg vs 1 mg intravitreal
1746
triamcinolone for the secondary efficacy outcome variables listed below. The secondary
1747
efficacy outcomes include the following:
1748
• Change between baseline and each efficacy outcome assessment visit in best-
1749
corrected ETDRS visual acuity score (e.g., mean change from baseline in visual
1750
acuity, distribution of change from baseline in visual acuity based on clinically
1751
meaningful cut points of improvement or worsening of visual acuity).
1752
• Change in calculated retinal thickening as assessed by optical coherence
1753
tomography.
1754
• Change in retinal thickness at the center of the macula as assessed by stereoscopic
1755
color fundus photography.
1756
• Change in area of retinal thickening as assessed by stereoscopic color fundus
1757
photography.
1758
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1759
6.7 Statistical Guidelines for Interim Monitoring by the DSMC
1760
6.7.1 Interim Monitoring for Safety
1761
The SCORE Study will use repeated confidence intervals to continuously monitor the
1762
safety indicator variables mentioned in section 6.5. Safety rates will be reported
1763
separately in the two disease areas, but injection arms will be pooled to increase
1764
accuracy of the estimates.
1765
1766
6.7.2 Interim Monitoring for Efficacy
1767
The primary efficacy outcome occurs at 12 months from the randomization visit. The
1768
recruitment pattern is unpredictable. Information concerning the primary outcome
1769
will accrue as participants complete their 12-month visit and thus "information time"
1770
is the percent of the 486 patients in each trial expected to have completed this visit.
1771
1772
Of the Type I error (alpha) = .05 for each trial, alpha = 0.005 will be allocated for
1773
interim monitoring and the remaining alpha = 0.045 will be reserved for the final
1774
analysis. With alpha =0.045 for the final analysis, the estimate of the sample size
1775
does not need to be increased for interim monitoring. Interim testing will be carried
1776
out using the Lan-DeMets interim monitoring boundary with an O’Brien-Fleming-
1777
type spending function where at most 0.005 cumulative alpha can be spent prior to the
1778
final analysis. The "height of the hurdle" is highest when the information fraction is
1779
smallest and decreases as additional patients complete 12 months. The "height of the
1780
hurdle" can be calculated for each DSMC meeting based on the number of patients
1781
expected to have completed the 12-month visit and the alpha spent by previous
1782
"looks" by the DSMC. With the specification that the total alpha for interim
1783
monitoring is 0.005, the maximum amount the DSMC can "spend" is 0.005. If the
1784
DSMC looks more often, it will “spend” less per look.
1785
1786
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Formally, if t is the information fraction, B(t) is the 2-sided cumulative O’Brien-
1787
Fleming-type spending function of Lan & DeMets with final value B(1) = 0.005, and
1788
S(t) is the two-sided cumulative spending function used by SCORE, then
1789
( ) for 0
1
( )
0.05 for
1
B t
t
S t
t
≤<
=
=
1790
1791
At each interim inspection, the three comparisons will be made using the Lan-DeMets
1792
methodology, and the results combined using Hochberg’s sequentially rejective
1793
procedure as described in the MOPP, section 6.4.
1794
6.7.3 Interim Monitoring for Futility
1795
The DSMC will consider futility as well as safety and efficacy. One method of
1796
statistically assessing futility is to use conditional power to estimate the likelihood of
1797
statistical significance given the observed efficacy results and various possible
1798
choices for the remaining results.
1799
1800
6.7.4 Analyses and Results Requested to be Considered Prior to
1801
Recommending Early Termination
1802
1803
Before recommending early termination, the DSMC will consider:
1804
• internal consistency of primary and secondary results
1805
• internal consistency of primary and secondary results by subgroups
1806
defined by baseline characteristics (e.g. visual acuity categories, categories
1807
based on length of history of CRVO or BRVO, and time period of
1808
enrollment)
1809
• distribution of baseline prognostic factors among the three groups
1810
(standard care, 4 mg, 1 mg)
1811
• consistency of primary and secondary results across clinical centers and
1812
among centers enrolling larger numbers of patients
1813
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• possible bias in assessment of primary and secondary response variables,
1814
particularly visual acuity, given the unmasked implementation of standard
1815
care versus intravitreal triamcinolone
1816
• possible impact of missing data from missed patient visits for assessment
1817
of the primary and secondary response variables
1818
• possible differences in concomitant interventions or medications.
1819
6.7.5 Study Timeline and DSMC Data Reviews
1820
The DSMC will meet to review study data starting in November 2004, and every 6
1821
months until 3-year follow-up is concluded on all study participants. Table 6 depicts
1822
the fractions of the population enrolled, with 1 year follow-up, and with 3 year
1823
follow-up, assuming that enrollment is constant, starts in August 2004, and takes 18
1824
months. Under this assumption, there will be 10 DSMC meetings. Formal interim
1825
inspection for 1-year efficacy will take place only during the four meetings when the
1826
information fraction is nonzero, that is, in November and May of 2005 and 2006.
1827
1828
Table 6: Study Timeline for DSMC Data Reviews
1829
1830
Date of DSMC Meeting
Fraction
Enrolled
With 1-year
follow-up
With 3-year
follow-up
November 2004
2/9
May 2005
5/9
November 2005
8/9
2/9
May 2006
1
5/9
November 2006
8/9
May 2007
1
November 2007
2/9
May 2008
5/9
November 2008
8/9
May 2009
1
1831
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7.
Confidentiality and Access to Source Data / Documents
1832
The investigators will maintain the highest degree of confidentiality permitted for the clinical and
1833
research information obtained from participants in this clinical study. Medical and research
1834
records should be maintained in the strictest confidence. However, as part of the quality
1835
assurance and legal responsibilities of an investigator, the site must permit authorized
1836
representatives of the sponsor(s), the SCORE Coordinating Center, and regulatory agencies to
1837
examine (and when permitted or required by applicable law, to copy) clinical records for the
1838
purposes of quality assurance reviews, audits and evaluation of the study safety and progress.
1839
Unless required by the law, no copying of records with personally identifying information will be
1840
permitted. Only the coded identity associated with documents or other participant data may be
1841
copied (obscuring any personally identifying information) or transmitted to the SCORE
1842
Coordinating Center. Authorized representatives as noted above are bound to maintain the strict
1843
confidentiality of medical and research information that may be linked to identified individuals.
1844
The site will normally be notified in advance of monitoring and auditing visits.
1845
1846
8.
Summary of Good Clinical Practice Compliance
1847
This trial will be conducted in accordance with Good Clinical Practice (GCP) using the guidance
1848
documents and practices offered by ICH and FDA, and in accordance with the Declarations of
1849
Helsinki and the policies and procedures for the SCORE Coordinating Center at The EMMES
1850
Corporation. This study will also comply with the regulations under 21 CFR Parts 50, 54, 56,
1851
and 312 under an IND application authorized by FDA.
1852
1853
8.1 Investigator Responsibilities (Form FDA-1572)
1854
A Statement of Investigator (Form FDA-1572) including the names of all of the
1855
sub-investigators and selected key study personnel (e.g., pharmacist, study nurse and/or
1856
study Coordinator, ophthalmic technician or optometric staff may be listed if desired)
1857
directly involved in the study will be completed and signed by the Principal Investigator at
1858
each site. The general responsibilities of the Investigator as acknowledged on the Form
1859
FDA-1572 are governed under the regulations in 21 CFR Parts 50, 54, 56, 312, and HIPAA.
1860
The study drug or test article may be administered only in accordance with the approved
1861
protocol and under the supervision of the Investigator or a sub-investigator listed on this
1862
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form. The Investigator must maintain accurate and complete study records, including
1863
records for disposition of the test article, and an accurate and complete record of all
1864
submissions made to and received from the local Institutional Review Board (IRB) or
1865
Independent Ethics Committee (IEC), including a copy of all reports and documents
1866
submitted. Adverse experiences that are reported to the FDA as IND Safety Reports must
1867
be submitted promptly to the local IRB/IEC and the SCORE Coordinating Center.
1868
1869
Progress reports must be submitted by the Investigator to the IRB/IEC at least once per
1870
year. The IRB/IEC must be promptly notified of completion or termination of the study.
1871
Within three months of study completion or termination, a final report from the Investigator
1872
must be provided to the IRB/IEC.
1873
1874
The curriculum vitæ (CV) or a résumé for each investigator, sub-investigator, and key study
1875
personnel must also be supplied if named on the Form FDA-1572. This form and related
1876
CVs must be supplied to the SCORE Coordinating Center prior to initiating the trial at each
1877
site. When necessary due to personnel changes, updated versions of the Form FDA-1572
1878
must be forwarded to the SCORE Coordinating Center and copies of all versions must be
1879
maintained in study records at each site. Any CV or résumé collected at the beginning of a
1880
study should be current, and would need to be updated during the study only if substantial
1881
changes or additions are warranted (e.g., change of position or affiliation, certifications or
1882
licensure, or significant new publications relevant to the study protocol).
1883
1884
8.2 Human Subjects Protection
1885
8.2.1 Institutional Review Board or Independent Ethics Committee
1886
Each participating institution must have an IRB or IEC constituted and operating in
1887
accordance with the regulations under 21 CFR Part 56 and authorized by the
1888
institution to review and approved materials for this trial. Because of the use of US
1889
Federal funds in this trial, all participating institutions must have a current Assurance
1890
of Compliance (either FWA or MPA) regarding their IRB/IEC on file with the DHHS
1891
Office of Human Research Protections (OHRP) before any award can be made to that
1892
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institution and before participants may be enrolled in the trial. In addition, each
1893
reviewing IRB or IEC must be registered with OHRP. A list of IRB/IEC voting
1894
members, their titles or occupations, and their institutional affiliations, as well as a
1895
copy of the Assurance of Compliance, must be kept available by the institution for
1896
inspection and copying by authorized study monitors, auditors, and regulatory
1897
officials.
1898
1899
8.3 Data Handling and Recordkeeping
1900
The Principal Investigator at the Participating Clinical Center is responsible for maintaining
1901
adherence to study procedures within the clinic. He or she must spend adequate time at the
1902
clinic observing study procedures and must hold regular discussions with staff, either
1903
one-to-one or in-group meetings, to review various aspects of the study and to solve
1904
problems that may arise. Other clinic staff members have a responsibility to report to the PI
1905
problems that could affect the quality of the data. The PI will designate one staff member
1906
to be the Clinic Coordinator for the clinic, with specific responsibility for reporting
1907
problems that have affected or can potentially affect the quality of data collected.
1908
1909
The Clinic Coordinator should be thoroughly familiar with clinic activities and equipment
1910
and the MOPP. The Clinic Coordinator should maintain an up-to-date copy of the MOPP
1911
close at hand and encourage all clinic personnel to consult it frequently. During Full Group
1912
Meetings the Clinic Coordinators will have the opportunity to meet with the Protocol
1913
Monitor to discuss mutual problems.
1914
1915
8.3.1 Case Report Forms
1916
Clinical data will be entered on electronic Case Report Forms (CRFs) in accordance
1917
with the procedures specified in the current MOPP and Data Management Handbook
1918
(DMH) for this trial.
1919
1920
8.3.2 Data Transmittal
1921
The primary method of data transmittal to the SCORE Coordinating Center will be via
1922
the secure AdvantageEDC maintained by The EMMES Corporation. The current
1923
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MOPP, DMH and access to the AdvantageEDC are available to authorized users via
1924
the SCORE DCC Internet web site, located at http://www.emmes.com/ where an
1925
assigned username and password are required for access. All data transfers between
1926
the investigational site and SCORE DCC via the AdvantageEDC are encrypted using
1927
SSL technologies to assure confidential data transfer.
1928
1929
8.4 Professional Licensure
1930
Physicians must provide evidence of current medical licensure applicable to the study
1931
location(s) if they are practicing medicine and undertake to diagnose and/or treat
1932
participants (including administration of the test article) in this study. A physician who is a
1933
site Principal Investigator must also provide evidence of ophthalmology training before
1934
study initiation.
1935
1936
8.5 Human Subjects Protection Training
1937
Documented training is required for each of the key personnel in the ethical conduct of
1938
clinical studies and in the protection of human subjects.
1939
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9.
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47. Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of
cataracts. New Engl J Med 1997;337:8-14.
48. Butcher JM. Austin M, McGalliard, Bourke RD. Bilateral cataracts and glaucoma
induced by long term use of steroid eye drops. BMJ 1994;309:43.
49. Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroids use with cataract
extraction in elderly patients. JAMA 1998;280:539-543.
50. Aaberg TM Jr, Flynn HW Jr. Nosocomial postoperative endophthalmitis. Invest Ophthalmol
Vis Sci 1996; 37: S775.
51. Endophthalmitis Vitrectomy Study Group. Results of the endophthalmitis vitrectomy
study. Arch Ophthalmol 1995;113:1479-1496.
52. Hida T, Chandler D, Arena J, Machemer R. Experimental and clinical observations of
the intraocular toxicity off commercial corticosteroid preparations. Am J Ophthalmol
1986; 101:190-195.
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
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53. Musch DC, Lichter PR, Guire KE, Standardi CL and the CIGTS Study Group. The
Collaborative Initial Glaucoma Treatment Study, Study Design, Methods, and Baseline
Characteristics of Enrolled Patients. Ophthalmology 1999;106:653-662.
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
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10. Appendix I
The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study
February 10, 2008
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Appendix 1: Scheduled Study Evaluations
Baseline
4-month interval follow-up visits
Safety2
M4
M8
M12
M16
M20
M24
M28
M32
M36
D4
M1
Informed
consent
X
Urine
pregnancy test
X3
Medical/ocular
history
X3
Blood pressure
X3
X
X
X
Visual acuity
X4,5
X5
X5
X5
X5
X5
X5
X5
X5
X5
X7
X7
Manifest
refraction
X5
X5
X5
X5
X5
IOP
X3,5
X5
X5
X5
X5
X5
X5
X5
X5
X5
X7
X7
Ophthalmic
examination8
X3,5
X5
X5
X5
X5
X5
X5
X5
X5
X5
X7
X7
Lens
assessment9
X3,5
X5
X5
X5
X5
Fundus photos
Study Eye
M7F3
M3F
M3F
M7F
M3F
M3F
M7F
M3F
M3F
M7F
Non-study Eye
M3F3
M3F
M3F
M3F
FA
X3
X
X
X
OCT
X5,10
X5
X6
X5
X6
X6
X5
X6
X6
X5
Steroid
injection
/Laser1
X
X
X
X
X
X
X
X
X
M= month
M7F= Modified 7-Field photos
Q= every
M3F= Modified 3-Field photos
D= day
1
Retreatment with steroid injections or laser photocoagulation (if applicable) should be administered at 4-month intervals
unless there are specific reasons not to treat in which case the investigator may decide to postpone treatment (see protocol
section 4.8.3).
2
Safety visits are performed at Day 4 and Month 1 after each injection.
3
To be performed within 21 days prior to randomization.
4
To be performed within 8 days prior to randomization
5
Examination data to be collected on both eyes.
6
Examination data to be collected on study eye only.
7
Examination data to be collected on the injected eye only.
8
Examination includes both a dilated fundus examination and a slit-lamp examination.
9
To be performed using the modified AREDS lens grading system.
10
OCT measurements will be performed twice on the same day in both eyes. This will occur within 21 days prior to
randomization.
Note: Visit windows at M8, M16, M20, M28, M32 may be extended, if necessary, so that the visit
occurs no sooner than 3.5 months from the last treatment.
ICF_001.pdf:
SCORE Study Informed Consent version 5.0
October 6, 2006
1
INFORMED CONSENT: The Standard Care versus COrticosteroid for REtinal Vein
Occlusion (SCORE) Study
TITLE OF PROJECT: The Standard Care versus COrticosteroid for REtinal Vein Occlusion
(SCORE) Study: Two Randomized Trials to Compare the Efficacy and Safety of Intravitreal
Injection(s) of Triamcinolone Acetonide with Standard Care to Treat Macular Edema: One for
Central Retinal Vein Occlusion and One for Branch Retinal Vein Occlusion
PURPOSE OF THE STUDY
Request to participate:
You are being asked to participate in this research study because you have macular edema
(swelling in the center of the retina) from a blockage in a retinal vein (a retinal blood vessel):
either a central retinal vein occlusion (CRVO) (a blockage in a larger retinal blood vessel) or
branch retinal vein occlusion (BRVO) (a blockage in a smaller retinal blood vessel). The study
is designed to find out if injection(s) of steroid into the eye are safe and effective in the treatment
of macular edema compared to standard treatment.
Triamcinolone acetonide is a steroid approved by the United States Food and Drug
Administration (FDA) for injection into joints and muscles for treatment of inflammatory
conditions. Triamcinolone acetonide works by reducing inflammation (swelling). Triamcinolone
acetonide has not been approved by the FDA for use in the eye, and is considered an
investigational drug when used to treat macular edema (eye disease).
Several thousand patients have received injections into the eye of a preparation of triamcinolone
acetonide called Kenalog. Kenalog is not made to use in the eye. Use of Kenalog has been
associated with eye inflammation in some patients and it is believed that this may be because
there are preservatives along with the triamcinolone acetonide in the Kenalog preparation. The
preparation of triamcinolone acetonide being used in the study is specially made for injection
into the eye and does not contain any preservatives.
Your participation in this study is voluntary. The study procedures and the possible risks,
discomforts and benefits of participation are described below. Please read the information
carefully and discuss any questions you have with your doctors before you decide whether or not
to participate.
If you choose to participate in this study, you must sign this form, which includes your
authorization for the use and disclosure of your health information that is collected as part of
your participation in this study. If you do not provide permission for the use and disclosure of
your health information, you will not be able to participate in this study.
Background:
The retina is a part of the eye that is similar to the film in a camera and produces images for the
brain to understand. The macula is the part of the retina that you use to read or see fine detail.
Retinal veins drain blood away from the retina back to your heart. A blockage in one of the large
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October 6, 2006
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retinal veins (central retinal vein occlusion - CRVO) or smaller retinal veins (branch retinal vein
occlusion - BRVO) can result in fluid in the center of the retina (macular edema). This can result
in decreased vision in that eye. Injecting a steroid directly into your eye may improve the vision
in your eye, but also carries risks. This study is being done to compare the risks and benefits of
this treatment.
If the vision loss is due to fluid in the retina associated with CRVO, laser treatment has not been
shown to improve the vision. No other proven treatments are available to try to improve the
vision. In some cases, vision may improve without treatment over many months to years. If you
have a CRVO, standard care consists of observation of the fluid in the retina as well as
monitoring the eye for the development of other complications such as increased eye pressure or
the growth of abnormal blood vessels which may require treatment. For patients with CRVO,
this study is designed to find out if injection(s) of steroid into the eye is safe and if this can lead
to improved vision compared with patients with CRVO who receive standard care (observation).
If the vision loss is due to fluid in the retina associated with BRVO, laser treatment alone has
been proven to help restore the vision in some patients. However, despite laser treatment, there
are some patients who do not experience an improvement in vision and improved treatments for
this condition need to be developed. If you have a BRVO, standard treatment consists of laser
treatment to the retina if excessive blood is not present in the retina along with fluid in the retina
(macular edema). If excessive blood is present in the retina, standard treatment consists of
observation until enough blood has been reabsorbed so that laser treatment can be performed.
For patients with BRVO, this study is designed to find out if injection(s) of steroid into the eye is
safe and if this can lead to improved vision compared with patients with BRVO who receive
standard care (observation or laser treatment to the retina, depending on how much blood is
present in the retina).
Purpose:
The purpose of this study is to find out if injection(s) of triamcinolone acetonide into the eye are
safe and effective in the treatment of macular edema in eyes with central retinal vein occlusion
(CRVO) or branch retinal vein occlusion (BRVO) compared to standard treatment.
PROCEDURE
Approximately 972 people will participate in this study at various medical centers in the United
States. There will be at least 12 study visits over a period of up to 3 years if you are assigned to
a group that is to receive injection(s). If you are assigned to a standard care group, there will be
at least 10 study visits over a period of 3 years. If you are assigned to a group that is to receive
injection(s) or if you receive laser treatment as part of the standard care group, you may require
additional visits, depending on whether or not you require additional treatment.
If you agree to participate in this study, you will have some tests to see if you are eligible. You
will be asked questions about your medical and medication history, and you will have your blood
pressure measured. If you are a woman and can bear children you will be asked to give a urine
sample to see if you are pregnant. See Section on Pregnancy and Contraception.
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In addition, you will have a complete eye examination for both eyes, including:
• Visual acuity: You will be asked to read letters on a special eye chart.
• Fluorescein angiography: Fluorescein angiography is a test in which a dye is injected into a
vein in your arm. The dye travels throughout the body, including the eyes. With a camera
and flashes of light, a series of photographs of the retina is taken as the dye passes through it.
The photographs will show where and what kinds of changes have occurred in the retina.
The test takes about 20 minutes.
• Optical coherence tomography (OCT): This is a test that uses a light source to examine
the retina and measure the thickness of the retina. You will be asked to sit in front of the
machine and you will be asked by either a technician or photographer to look into a pattern
of flashing and rotating red and green lights first with one eye then the other. The procedure
takes approximately 5 minutes per eye to perform.
• Eye examination: An assessment of the cornea, lens, and retina, after dilating drops have
been administered, will be performed. Also, the pressure in your eyes will be measured.
During some of the eye examinations, fundus photography will be performed. Fundus
photography is a procedure in which bright lights will be shone into your eyes and pictures will
be taken of the back of your eye (retina).
If your study doctor determines that you are eligible for the study, you will be randomly assigned
(by chance, like the flip of a coin) to receive either injection(s) of triamcinolone acetonide or
standard treatment. If you have CRVO, standard treatment is observation. If you have BRVO
and an excessive amount of blood in the retina, standard treatment is observation. If you have
BRVO and excessive blood is not present in the retina, standard treatment is laser treatment.
If both of your eyes meet the criteria for being part of the study, only one of your eyes will be
randomly selected to receive either steroid injection(s) or standard treatment. The other eye
cannot be entered into the study.
If you are randomized to receive an injection of steroid medication, you will receive one of 2
doses (4 mg or 1 mg). This study is designed such that you have a 1 in 3 (33%) chance of
receiving a steroid injection with the 4 mg dose, a 1 in 3 (33%) chance of receiving a steroid
medication with the 1 mg dose, and a 1 in 3 (33%) chance of receiving standard treatment.
During the study period, you will be examined at least every 4 months and, depending on how
your eye responds to treatment, you may be retreated as often as every 4 months. Thus, if you
are randomized to receive steroid injection(s), you may receive an injection as often as every 4
months. Similarly, if you have a BRVO that does not have excessive blood present in the retina
and are randomized to standard treatment, you may receive multiple laser treatments.
Before receiving the injection with triamcinolone acetonide, a local anesthetic (numbing
medication) will be placed with a cotton tipped applicator into the lower part of your eye in the
clear tissue that surrounds the white of your eye. Regardless of the diagnosis of your macular
edema (CRVO or BRVO), if you are assigned to receive triamcinolone acetonide, after a few
minutes, the study drug will be injected into your vitreous, which is the jelly-like substance
inside your eye located between the back of your lens and your retina. If you are assigned to a
standard treatment arm, no injection will be given. If you receive an injection, before leaving,
SCORE Study Informed Consent version 5.0
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your doctor will give you an antibiotic eyedrop to place in your eye for 3 days following the
injection.
For the laser treatment procedure, if you are assigned to a standard care group and your eye
doctor determines that laser treatment to the retina may benefit you, 1 or 2 drops of a numbing
agent are applied to the surface of the eye. A special contact lens is then placed on the eye
during the laser beam application. You will be asked to remain still while the laser beam is
applied. Minimal discomfort is anticipated during the laser beam treatment.
If you have BRVO and are assigned to a standard treatment arm, you will receive immediate
laser treatment unless there is too much blood in the retina to permit laser treatment to be given.
If your doctor is unable to perform laser treatment at the time you enroll in the study because
there is too much blood in the retina, you will be observed and laser treatment will be given if the
blood clears enough to permit application of laser treatment.
If you have CRVO, no laser treatment will be given for macular edema, regardless of your
assignment to the treatment arms.
Follow-up visits will occur at least every 4 months. The need and timing of additional visits
depends on your course of treatment. For example, if you receive an injection, you will also be
examined within 1 week of each injection and 1 month following each injection. At each visit,
your vision will be checked. Your eyes will be dilated for an eye examination and the pressure
of your eye measured. Photographs of your retina will be taken, and OCT will be performed at
certain study visits. Fluorescein angiography will be performed at Months 4, 12, and 24. In
addition, at Months 12, 24, and 36 you will have your blood pressure measured.
RISKS
Possible risks of the injection include the following:
1) We anticipate an approximately 100% chance of seeing floaters (things floating around
inside your eye), which almost always resolve within a few days to weeks.
2) We anticipate a low chance [estimated at less than 1 in 100 (1%)] of retinal detachment
(separation of the film-like layer of cells at the back of the eye) which may require
surgery to treat. If a retinal detachment occurs and surgery is required, the surgery is
usually successful. However, a retinal detachment can produce permanent loss of vision
and even blindness.
3) We anticipate a low chance [estimated at less than 1 in 100 (1%)] of vitreous hemorrhage
(bleeding in the gel inside the eye) which usually resolves within a few weeks. If it does
not go away, surgery may be needed to remove the blood. This surgery is usually
successful. However, a vitreous hemorrhage can produce permanent loss of vision and
even blindness.
4) We anticipate a low chance [estimated at less than 1 in 100 (1%)] of endophthalmitis
(infection of an entire eye) which would require treatment with antibiotic injections into
the eye and possibly surgery. This treatment is usually successful. However,
endophthalmitis can produce permanent loss of vision and even blindness.
5) Tiny droplets, about the size of the period on this page, have been observed in the
vitreous cavity following injection of the SCORE Study steroid preparation. As of
SCORE Study Informed Consent version 5.0
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October 5, 2006, this has been reported in 6 study participants out of 256 study
participants (2.3%) who have received an intravitreal steroid injection in the study.
These droplets have been reported before with intravitreal injection of various other
medications. The source of the droplets is believed to be silicone oil that is used as a
lubricant in the syringes and needles employed to deliver the medication. Silicone oil in
large amounts is sometimes put into the vitreous during retinal detachment surgery. The
amount of silicone oil in the eye after an intravitreal injection is a very tiny amount. We
do not have any evidence that droplets of silicone oil are harmful to the eye. None of the
participants in the study has reported any problems with their vision or any other
problems due to the droplets. It is possible that the droplets could cause you to see
floaters at certain times depending on the background in your field of view and the
lighting.
Possible risks associated with triamcinolone acetonide include the following:
1) We anticipate that many patients will experience cataract (clouding of the lens of the eye)
after treatment. We do not know how often a cataract develops from the steroid
injection. However, we think there is a good chance that a cataract will develop. If a
cataract develops, cataract surgery may be needed. In most cases, this surgery is
effective in removing the cataract.
2) An increase in eye pressure could happen right after the injection or it could happen
weeks to months later. If the eye pressure is high right after the injection, eye drops may
be given to help lower the eye pressure. If the pressure is still high, fluid may be
removed from the front part of the eye with a small needle. If the eye pressure goes up
after several weeks to months, eye drops may be needed to lower the eye pressure. If the
eye drops do not lower the eye pressure, it may be necessary to have surgery to lower the
eye pressure. There is an approximately 3 in 10 (30%) chance of increased pressure in
the eye which is usually reversible and can be treated with medications (e.g. eyedrops)
but may require surgery. It is estimated that the chance of requiring surgery to lower eye
pressure (called trabeculectomy surgery) is less than 1 in 20 (5%).
There may be additional conditions associated with the injection and triamcinolone acetonide
that are not known at this time.
Fluorescein angiography: After the orange-colored dye is injected into your arm, your skin
may turn yellow for several hours. The yellow color will disappear as your kidney removes the
dye from your body. Because the dye passes through your kidneys, your urine will turn dark
orange for up to 24 hours after the exam. Some participants may be slightly nauseous (upset
stomach) during the exam, but their nausea usually lasts only a few seconds, and rarely, some
may vomit. There is also a chance of fainting and a chance of bruising (black and blue mark) at
the site of injection. If the dye leaks out of your vein during the injection, some of the skin
around the injection site may feel like it is burning or become yellow. The burning sensation
usually lasts only a few minutes, and the yellow color goes away in a few days. As with any
drug, it is possible that you could experience an allergic reaction to the dye. Such allergic
reactions include: itching, skin rash, an acute or sudden drop in blood pressure to shock levels
with loss of consciousness and/or associated with seizures, including the possibility of death (the
risk of death is about 1 in 250,000).
SCORE Study Informed Consent version 5.0
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6
Optical coherence tomography (OCT): For the OCT, your pupils will be dilated. Your pupils
will remain dilated for 4 to 6 hours. This may result in excess glare in brightly lit areas.
Sunglasses will reduce this problem. You should not drive if your vision is impaired.
Risks of eye examination and dilation: Dilation of your pupils may cause some temporary
glare and blurring of vision. Occasionally, there may be an allergic reaction to the medication.
If this should occur, medication to control the allergic reaction will be administered. Rarely,
dilation may cause the pressure in the eye to go up; if this should occur, you will be treated with
eyedrops and, if necessary, laser surgery.
It is possible that complications and side effects of the study treatment that are unknown at this
time may occur. You will be told of any new findings that develop which may affect your
willingness to continue in the study.
PREGNANCY AND CONTRACEPTION
Pregnancy: If you are a woman and can bear children, you will have a urine pregnancy test at
the beginning of the study. If you are pregnant, you will not be allowed in the study. If you
become pregnant during the study, you must inform the physician or the study coordinator that
you are pregnant.
Contraception: The effect of the dye injected for the fluorescein angiography procedure on a
fetus is unknown. If you are a woman who is sexually active and can bear children, you or your
partner must use a reliable form of birth control from the time you enroll in the study until you
are no longer in the study.
BENEFITS
It is possible that you may not benefit from your participation in the study. No direct medical
benefit to you can be assured from your participation in this study. As a result of your
participation, your macular edema may improve; however, this cannot be guaranteed. If you are
randomized to a standard treatment arm, no therapy with the study drug will be given and,
therefore, you will not receive direct benefit from participation in this study. However,
information obtained in this study may be of future benefit to both you and other patients with
macular edema.
ALTERNATIVES
The information obtained from this study will have no bearing on your medical treatment. You
may choose to not participate in this study. For CRVO there are currently no proven treatments
available. For BRVO you may choose to undergo laser treatment if your doctor determines you
are eligible (for example, if there is not too much blood associated with the fluid in your retina)
or to receive no treatment at all.
SCORE Study Informed Consent version 5.0
October 6, 2006
7
CONFIDENTIALITY& YOUR PROTECTED HEALTH INFORMATION
(Section Required by the HIPAA Privacy Rule – 45 CFR 164.508)
By signing this form, you are giving permission for the use and disclosure of your health
information that is collected as part of your participation in this study.
A. What health information about you may be used or disclosed?
The results of your examinations and testing that are part of this study will be reported to the
SCORE Data Coordinating Center in Rockville, Maryland along with information from all other
participants in the study at this and all other participating clinics across the country. The
photographs of your eyes, angiograms, and OCTs from your evaluations will be sent to the Fundus
Photograph Reading Center for this study. The Fundus Photograph Reading Center is located at the
Department of Ophthalmology & Visual Sciences at the University of Wisconsin – Madison in
Madison, WI. This information will be identified to the SCORE Data Coordinating Center and the
Fundus Photograph Reading Center only by a code number assigned to you. Federal privacy
regulations provide safeguards for privacy, security, and authorized access. Except where required
by law and as noted in the paragraph below, you will not be identified by name, social security
number, address, telephone number, or any other direct personal identifier in study records
disclosed outside of your eye doctor’s office.
Results of the study will be reported in medical journals and may be presented at scientific
meetings. However, at no time will any of the patients in the study be identified in any publication
or at any meeting. Confidentiality of your records will be maintained and all records will be kept
in accordance with current legal requirements. The research team will discuss the results of your
tests with you during the study. You will be informed of the results of the study at the time they are
made public.
B. Who may use or disclose and see or receive your health information?
Reviewers of your health information may include representatives of the SCORE Data Coordinating
Center (Rockville, MD), the Fundus Photograph Reading Center (Madison, WI) and Pharmaceutical
Partner (Allergan, Inc., Irvine, CA) who are involved in the conduct of the study, the analysis of the
data and the manufacturing of the study drug, any review board that oversees human investigations
regulations for your doctor’s office or institution, or any federal agency that oversees the conduct of
clinical trials. If your research record is reviewed by any of these groups, they may also need to
review your entire medical record.
C. Why do they need to see or receive your health information?
As part of this study, the persons or entities listed above (see paragraph B) may see, receive, or
use your health information to help conduct the study and/or to evaluate the results. Your records
may also be reviewed in order to meet federal or state regulations.
D. Is there an expiration date?
No. Your authorization for the use and disclosure of your health information will continue
indefinitely.
SCORE Study Informed Consent version 5.0
October 6, 2006
8
E. May you stop or cancel your permission for the use and disclosure of your health
information?
Yes. You may stop or cancel your permission for the use and disclosure of your health
information at any time. You need only to contact your doctor or one of the medical staff at
(telephone number) and provide a notice of cancellation to him/her in writing. However, when
you stop or cancel your permission for the use and disclosure of your health information, you
will no longer be part of the study.
When you stop or cancel your permission for the use and disclosure of your health information
or when you withdraw from the study directly, no new data about you will be collected for study
purposes unless the data concern an adverse event (a bad effect) related to the study. If such an
adverse event occurs, your entire medical record may need to be reviewed. All data that have
already been collected for study purposes up to the time of cancellation or withdrawal, and any
new information about any adverse event related or potentially related to the study, will be sent
to the SCORE Data Coordinating Center.
F. Is your health information protected after it has been given to others?
It is possible that your health information may be given out or disclosed again if the recipients
named above (see paragraph B) are not required by law to protect the privacy of your health
information. The SCORE Study DCC will make very effort to comply with the Privacy
Regulations as required by law.
FINANCIAL RESPONSIBILITY
Any costs borne by you that may result from your participation in this study are your
responsibility. The triamcinolone acetonide (study drug) will be provided at no cost to you. All
other charges associated with your continuing medical care, including the injection procedure (if
applicable), the traditional laser treatment (if applicable), photography and room charges, will be
billed to you or your insurance provider in the normal fashion. If you develop a complication as a
result of participation in this study (e.g. cataract or glaucoma) and require treatment for the
complication (e.g. cataract surgery or surgery for glaucoma), the cost of the cataract surgery or
surgery for glaucoma will be billed to you or your insurance provider in the normal fashion.
If you experience an unexpected adverse reaction as a direct result of the study drug being
administered in this study, your reasonable expenses for medical treatment of such reaction will
be reimbursed by the drug manufacturer, Allergan, to the extent that these expenses are not
covered by medical, third party, or government insurance or programs.
In select cases, reimbursement for travel related expenses may be available as need warrants.
COMPENSATION AND INJURY STATEMENT
If injury occurs due to your involvement in this study, medical treatment will be available. You
or your insurance company will be responsible for the costs of this medical care, unless you
experience an unexpected problem that is a direct result of the new formulation of triamcinolone
being administered in this study. If this should occur, your reasonable expenses for medical
treatment of such reaction will be reimbursed by the drug manufacturer, Allergan, to the extent
SCORE Study Informed Consent version 5.0
October 6, 2006
9
that these expenses are not covered by medical, third party, or government insurance or
programs. Compensation for lost wages and/or direct or indirect losses is not available.
VOLUNTARY PARTICIPATION AND WITHDRAWAL STATEMENT
You may withdraw from the research study at any time. Your participation is completely
voluntary. You may stop participating at any time, and you may refuse to answer any question if
you don’t wish to answer. Even if you do not want to join the study, or if you stop participating
in it, you will still have the same quality of medical care available to you at the local site. The
investigators reserve the right to remove you from the study without your consent at such time
that they feel it is in your best interest medically or for administrative reasons.
OFFER TO ANSWER ANY QUESTIONS
In case of a research-related injury, or if you have any questions, please contact Dr. X (Principal
Investigator) at X (XXX) XXX-XXXX. You may ask questions in the future if you do not
understand something that is being done. If you have any questions regarding your rights as a
study subject, you may contact the Institutional Review Board administrator (Lesley S. Zajac at
1-813-975-8690). You will be given a signed copy of this form to keep. You will be informed
of significant new findings that may alter your continued participation in this study.
Subject's Name (printed)
Description of Representative’s Authority to Act for the Study Subject
__________________________________________________ (if applicable)
AGREEMENT TO HAVE THE TESTING DONE TO SEE IF I AM ELIGIBLE FOR THIS STUDY
By signing below, I agree to have this testing done. I authorize the use and disclosure of my
health information collected as part of the eligibility testing.
_________________________________________
_____________
Signature of Subject or Authorized Representative
Date
_________________________________________
_____________
Witness
Date
APPROVAL DATE
Jaeb Center for Health Research
Institutional Review Board
JUL 09 2007
SCORE Study Informed Consent version 5.0
October 6, 2006
10
AGREEMENT TO PARTICIPATE IN THIS STUDY
I have read the explanation about this study. I have been given the opportunity to discuss the
study and to ask questions. I hereby give my consent to take part in this study. I authorize the
use and disclosure of my health information collected as part of my participation in this study.
_________________________________________
_____________
Signature of Subject or Authorized Representative
Date
_________________________________________
_____________
Witness
Date
I have personally explained the research to the subject or the subject’s legally authorized
representative and answered all questions. I believe that he/she understands the information
described in this informed consent and freely consents to participate.
______________________________________
Signature of person obtaining informed consent
APPROVAL DATE
Jaeb Center for Health Research
Institutional Review Board
JUL 09 2007
| 6
|
arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None
|
[
1,
1,
1,
1,
1,
1
] | 3
|
[
10,
0,
0
] |
intervention 1: CRVO: observation; BRVO: standard care intervention 2: 1 mg dose intervention 3: 4 mg
|
intervention 1: Standard Care intervention 2: intravitreal triamcinolone injection intervention 3: intravitreal triamcinolone injection
| 1
|
Madison | Wisconsin | United States | -89.40123 | 43.07305
| 0
|
NCT00105027
|
[
4
] | 19
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
RATIONALE: Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin and docetaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) together with radiation therapy before surgery may shrink the tumor so it can be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving cisplatin and docetaxel together with radiation therapy is more effective than giving cisplatin together with docetaxel in treating non-small cell lung cancer.
PURPOSE: This randomized phase III trial is studying cisplatin, docetaxel, and radiation therapy to see how well they work compared to cisplatin and docetaxel in treating patients who are undergoing surgery for newly diagnosed stage III non-small cell lung cancer.
|
OBJECTIVES:
Primary
* Compare overall survival of patients with newly diagnosed favorable prognosis stage IIIA non-small cell lung cancer treated with neoadjuvant cisplatin and docetaxel with vs without thoracic conformal radiotherapy followed by surgical resection and docetaxel.
Secondary
* Compare median and progression-free survival of patients treated with these regimens.
* Compare clinical and pathologic response rates in patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
* Correlate pathological complete response with disease-free and overall survival of patients treated with these regimens.
* Correlate DNA damage repair genes (ERCC1 and XRCC1), microtubule-related proteins (TUBB-III and MAP4), and shed tumor DNA with response and outcome in patients treated with these regimens.
* Correlate protein profiles, using MALDI-TOF proteomic analysis of tumor and serum, with response and prognosis in patients treated with these regimens.
* Compare quality of life of patients treated with these regimens.
* Determine the efficacy of fludeoxyglucose F 18 positron emission tomography scanning in assessing pathological response of the tumor and the mediastinal lymph nodes and in predicting long-term outcome in patients treated with these regimens.
* Correlate comorbid conditions with survival of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T stage (T1 vs T2-3), number of involved mediastinal lymph nodes (1 vs 2 or more vs not evaluable), and nodal micrometastases vs clinically involved nodes (mN2 vs cN2).
* Induction therapy: Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive cisplatin IV over 1 hour and docetaxel IV over 1 hour on days 1 and 22.
* Arm II: Patients undergo thoracic conformal radiotherapy once daily 5 days a week for approximately 5½ weeks (total of 28 doses). Patients also receive cisplatin IV over 1 hour on days 1, 8, 22, and 29 and docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29.
* Surgery: Within 4-8 weeks after completion of induction therapy, patients with stable disease or better undergo a lobectomy or pneumonectomy with a formal systematic mediastinal lymph node dissection.
* Consolidation therapy: Beginning 4-6 weeks after surgery, patients receive docetaxel IV over 1 hour on days 1, 22, and 43 and pegfilgrastim or filgrastim (G-CSF) subcutaneously on days 2, 23, and 44.
Quality of life is assessed at baseline, within 2 weeks after completion of induction therapy, and then at 6 and 12 months after surgery.
After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 574 patients will be accrued for this study within 4 years.
|
Lung Cancer
|
stage IIIA non-small cell lung cancer adenocarcinoma of the lung large cell lung cancer squamous cell lung cancer bronchoalveolar cell lung cancer
| null | 2
|
arm 1: Induction/surgery/consolidation arm 2: Induction/radiation/surgery/cosolidation
|
[
5,
5
] | 8
|
[
2,
2,
0,
0,
3,
3,
3,
4
] |
intervention 1: Consolidation chemotherapy intervention 2: Consolidation chemotherapy intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None
|
intervention 1: filgrastim intervention 2: pegfilgrastim intervention 3: cisplatin intervention 4: docetaxel intervention 5: adjuvant therapy intervention 6: conventional surgery intervention 7: neoadjuvant therapy intervention 8: radiation therapy
| 76
|
Anchorage | Alaska | United States | -149.90028 | 61.21806
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Concord | California | United States | -122.03107 | 37.97798
La Jolla | California | United States | -117.2742 | 32.84727
Los Angeles | California | United States | -118.24368 | 34.05223
Sacramento | California | United States | -121.4944 | 38.58157
Colorado Springs | Colorado | United States | -104.82136 | 38.83388
Fort Collins | Colorado | United States | -105.08442 | 40.58526
Fort Collins | Colorado | United States | -105.08442 | 40.58526
Newark | Delaware | United States | -75.74966 | 39.68372
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jupiter | Florida | United States | -80.09421 | 26.93422
Lakeland | Florida | United States | -81.9498 | 28.03947
Miami Beach | Florida | United States | -80.13005 | 25.79065
Albany | Georgia | United States | -84.15574 | 31.57851
Atlanta | Georgia | United States | -84.38798 | 33.749
Gainesville | Georgia | United States | -83.82407 | 34.29788
Geneva | Illinois | United States | -88.30535 | 41.88753
Maywood | Illinois | United States | -87.84312 | 41.8792
Normal | Illinois | United States | -88.99063 | 40.5142
Oak Lawn | Illinois | United States | -87.75811 | 41.71087
Pekin | Illinois | United States | -89.64066 | 40.56754
Peoria | Illinois | United States | -89.58899 | 40.69365
Peoria | Illinois | United States | -89.58899 | 40.69365
Springfield | Illinois | United States | -89.64371 | 39.80172
Richmond | Indiana | United States | -84.89024 | 39.82894
South Bend | Indiana | United States | -86.25001 | 41.68338
Bettendorf | Iowa | United States | -90.51569 | 41.52448
Davenport | Iowa | United States | -90.57764 | 41.52364
Lexington | Kentucky | United States | -84.47772 | 37.98869
Baltimore | Maryland | United States | -76.61219 | 39.29038
Baltimore | Maryland | United States | -76.61219 | 39.29038
Frederick | Maryland | United States | -77.41054 | 39.41427
Boston | Massachusetts | United States | -71.05977 | 42.35843
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Marquette | Michigan | United States | -87.39542 | 46.54354
Rochester | Minnesota | United States | -92.4699 | 44.02163
Joplin | Missouri | United States | -94.51328 | 37.08423
Springfield | Missouri | United States | -93.29824 | 37.21533
St Louis | Missouri | United States | -90.19789 | 38.62727
Kearney | Nebraska | United States | -99.08148 | 40.69946
Omaha | Nebraska | United States | -95.94043 | 41.25626
Omaha | Nebraska | United States | -95.94043 | 41.25626
Ridgewood | New Jersey | United States | -74.11653 | 40.97926
New York | New York | United States | -74.00597 | 40.71427
Syracuse | New York | United States | -76.14742 | 43.04812
Utica | New York | United States | -75.23266 | 43.1009
Durham | North Carolina | United States | -78.89862 | 35.99403
Greenville | North Carolina | United States | -77.36635 | 35.61266
Kinston | North Carolina | United States | -77.58164 | 35.26266
Pinehurst | North Carolina | United States | -79.46948 | 35.19543
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Columbus | Ohio | United States | -82.99879 | 39.96118
Portland | Oregon | United States | -122.67621 | 45.52345
Portland | Oregon | United States | -122.67621 | 45.52345
Bethlehem | Pennsylvania | United States | -75.37046 | 40.62593
Hershey | Pennsylvania | United States | -76.65025 | 40.28592
Lancaster | Pennsylvania | United States | -76.30551 | 40.03788
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
York | Pennsylvania | United States | -76.72774 | 39.9626
Charleston | South Carolina | United States | -79.93275 | 32.77632
Greenville | South Carolina | United States | -82.39401 | 34.85262
Spartanburg | South Carolina | United States | -81.93205 | 34.94957
Knoxville | Tennessee | United States | -83.92074 | 35.96064
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Seattle | Washington | United States | -122.33207 | 47.60621
Seattle | Washington | United States | -122.33207 | 47.60621
Tacoma | Washington | United States | -122.44429 | 47.25288
Green Bay | Wisconsin | United States | -88.01983 | 44.51916
Madison | Wisconsin | United States | -89.40123 | 43.07305
Sheboygan | Wisconsin | United States | -87.71453 | 43.75083
| 0
|
NCT00113386
|
[
4
] | 15
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin and paclitaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) and giving them with radiation therapy may kill more tumor cells. It is not yet known whether giving radiation therapy together with combination chemotherapy is more effective than giving combination chemotherapy alone in treating head and neck cancer.
PURPOSE: This randomized phase III trial is studying radiation therapy and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating patients with recurrent head and neck cancer that cannot be removed by surgery.
|
OBJECTIVES:
Primary
* Compare overall survival of patients with previously irradiated unresectable locally recurrent squamous cell carcinoma of the head and neck treated with radiotherapy, cisplatin, and paclitaxel vs cisplatin-based chemotherapy alone.
Secondary
* Compare progression-free survival of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
* Compare quality of life, functional/performance status, and quality-adjusted survival of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients undergo radiotherapy twice daily and receive paclitaxel IV over 1 hour and cisplatin IV over 30 minutes once daily on days 1-5, 15-19, 29-33, and 43-47. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-13, 20-27, 34-41, and 48-55.
* Arm II: Patients receive 1 of the following cisplatin-based\* regimens at the discretion of the treating physician:
* Regimen 1: Patients receive cisplatin\* IV over 1-2 hours on day 1 and fluorouracil IV continuously over 96 hours on days 1-4.
* Regimen 2: Patients receive cisplatin\* IV over 1-2 hours and paclitaxel IV over 3 hours on day 1.
* Regimen 3: Patients receive cisplatin\* IV over 1-2 hours and docetaxel IV over 1 hour on day 1.
NOTE: \*Carboplatin may be substituted for cisplatin in patients with creatinine clearance \< 50 mL/min or in patients who experience grade 2 or 3 neurotoxicity.
For all regimens, treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond documentation of CR.
Quality of life is assessed at baseline and then at 3, 6, 12, 24, and 36 months.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study within 5½ years.
|
Head and Neck Cancer
|
recurrent squamous cell carcinoma of the hypopharynx recurrent squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the lip and oral cavity recurrent squamous cell carcinoma of the oropharynx recurrent metastatic squamous neck cancer with occult primary recurrent lymphoepithelioma of the oropharynx
| null | 2
|
arm 1: Radiotherapy/paclitaxel/cisplatin/filgrastim arm 2: Cisplatin/fluorouracil/paclitaxel/docetaxel
|
[
5,
5
] | 6
|
[
2,
0,
0,
0,
0,
4
] |
intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None
|
intervention 1: filgrastim intervention 2: cisplatin intervention 3: docetaxel intervention 4: fluorouracil intervention 5: paclitaxel intervention 6: radiation therapy
| 125
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Mobile | Alabama | United States | -88.04305 | 30.69436
Hot Springs | Arkansas | United States | -93.05518 | 34.5037
Auburn | California | United States | -121.07689 | 38.89657
Cameron Park | California | United States | -120.98716 | 38.66879
Carmichael | California | United States | -121.32828 | 38.61713
Pomona | California | United States | -117.75228 | 34.05529
Roseville | California | United States | -121.28801 | 38.75212
Sacramento | California | United States | -121.4944 | 38.58157
Sacramento | California | United States | -121.4944 | 38.58157
Sacramento | California | United States | -121.4944 | 38.58157
Vacaville | California | United States | -121.98774 | 38.35658
Boca Raton | Florida | United States | -80.0831 | 26.35869
Fort Lauderdale | Florida | United States | -80.14338 | 26.12231
Gainesville | Florida | United States | -82.32483 | 29.65163
Jupiter | Florida | United States | -80.09421 | 26.93422
Miami | Florida | United States | -80.19366 | 25.77427
Miami Beach | Florida | United States | -80.13005 | 25.79065
Tampa | Florida | United States | -82.45843 | 27.94752
Augusta | Georgia | United States | -81.97484 | 33.47097
Savannah | Georgia | United States | -81.09983 | 32.08354
Alton | Illinois | United States | -90.18428 | 38.8906
Aurora | Illinois | United States | -88.32007 | 41.76058
Joliet | Illinois | United States | -88.0834 | 41.52519
Olympia Fields | Illinois | United States | -87.67421 | 41.51337
Springfield | Illinois | United States | -89.64371 | 39.80172
Urbana | Illinois | United States | -88.20727 | 40.11059
Urbana | Illinois | United States | -88.20727 | 40.11059
Anderson | Indiana | United States | -85.68025 | 40.10532
Beech Grove | Indiana | United States | -86.08998 | 39.72199
Elkhart | Indiana | United States | -85.97667 | 41.68199
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Kokomo | Indiana | United States | -86.1336 | 40.48643
La Porte | Indiana | United States | -86.71389 | 41.60774
Michigan City | Indiana | United States | -86.89503 | 41.70754
Richmond | Indiana | United States | -84.89024 | 39.82894
South Bend | Indiana | United States | -86.25001 | 41.68338
South Bend | Indiana | United States | -86.25001 | 41.68338
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Waterville | Maine | United States | -69.63171 | 44.55201
Baltimore | Maryland | United States | -76.61219 | 39.29038
Adrian | Michigan | United States | -84.03717 | 41.89755
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
Detroit | Michigan | United States | -83.04575 | 42.33143
Lansing | Michigan | United States | -84.55553 | 42.73253
Saint Joseph | Michigan | United States | -86.48002 | 42.10976
Cape Girardeau | Missouri | United States | -89.51815 | 37.30588
Gape Girardeau | Missouri | United States | N/A | N/A
St Louis | Missouri | United States | -90.19789 | 38.62727
St Louis | Missouri | United States | -90.19789 | 38.62727
St Louis | Missouri | United States | -90.19789 | 38.62727
Billings | Montana | United States | -108.50069 | 45.78329
Billings | Montana | United States | -108.50069 | 45.78329
Billings | Montana | United States | -108.50069 | 45.78329
Omaha | Nebraska | United States | -95.94043 | 41.25626
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Keene | New Hampshire | United States | -72.27814 | 42.93369
Lebanon | New Hampshire | United States | -72.25176 | 43.64229
Marlton | New Jersey | United States | -74.92183 | 39.89122
Toms River | New Jersey | United States | -74.19792 | 39.95373
Vineland | New Jersey | United States | -75.02573 | 39.48623
Voorhees Township | New Jersey | United States | -74.49062 | 40.4795
Brooklyn | New York | United States | -73.94958 | 40.6501
Buffalo | New York | United States | -78.87837 | 42.88645
Manhasset | New York | United States | -73.69957 | 40.79788
Manhasset | New York | United States | -73.69957 | 40.79788
New Hyde Park | New York | United States | -73.68791 | 40.7351
Kinston | North Carolina | United States | -77.58164 | 35.26266
Rutherfordton | North Carolina | United States | -81.95677 | 35.36929
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Akron | Ohio | United States | -81.51901 | 41.08144
Akron | Ohio | United States | -81.51901 | 41.08144
Dayton | Ohio | United States | -84.19161 | 39.75895
Dayton | Ohio | United States | -84.19161 | 39.75895
Dayton | Ohio | United States | -84.19161 | 39.75895
Dayton | Ohio | United States | -84.19161 | 39.75895
Dayton | Ohio | United States | -84.19161 | 39.75895
Findlay | Ohio | United States | -83.64993 | 41.04422
Kettering | Ohio | United States | -84.16883 | 39.6895
Lima | Ohio | United States | -84.10523 | 40.74255
Maumee | Ohio | United States | -83.65382 | 41.56283
Middletown | Ohio | United States | -84.39828 | 39.51506
Oregon | Ohio | United States | -83.48688 | 41.64366
Salem | Ohio | United States | -80.85675 | 40.90089
Sandusky | Ohio | United States | -82.70796 | 41.44894
Sylvania | Ohio | United States | -83.71299 | 41.71894
Toledo | Ohio | United States | -83.55521 | 41.66394
Toledo | Ohio | United States | -83.55521 | 41.66394
Toledo | Ohio | United States | -83.55521 | 41.66394
Toledo | Ohio | United States | -83.55521 | 41.66394
Troy | Ohio | United States | -84.20328 | 40.0395
Wooster | Ohio | United States | -81.93646 | 40.80517
Wright-Patterson AFB | Ohio | United States | -84.05731 | 39.81113
Xenia | Ohio | United States | -83.92965 | 39.68478
Darby | Pennsylvania | United States | -75.25907 | 39.91845
Natrona Heights | Pennsylvania | United States | -79.72977 | 40.6234
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Anderson | South Carolina | United States | -82.65013 | 34.50344
Charleston | South Carolina | United States | -79.93275 | 32.77632
Spartanburg | South Carolina | United States | -81.93205 | 34.94957
Spartanburg | South Carolina | United States | -81.93205 | 34.94957
Rapid City | South Dakota | United States | -103.23101 | 44.08054
Sioux Falls | South Dakota | United States | -96.70033 | 43.54997
Sioux Falls | South Dakota | United States | -96.70033 | 43.54997
Murray | Utah | United States | -111.88799 | 40.66689
Ogden | Utah | United States | -111.97383 | 41.223
Provo | Utah | United States | -111.65853 | 40.23384
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Salt Lake City | Utah | United States | -111.89105 | 40.76078
St. George | Utah | United States | -113.58412 | 37.10415
Saint Johnsbury | Vermont | United States | -72.01509 | 44.41922
Morgantown | West Virginia | United States | -79.9559 | 39.62953
Madison | Wisconsin | United States | -89.40123 | 43.07305
Menomonee Falls | Wisconsin | United States | -88.11731 | 43.1789
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Racine | Wisconsin | United States | -87.78285 | 42.72613
Wausau | Wisconsin | United States | -89.63012 | 44.95914
West Milwaukee | Wisconsin | United States | -87.97259 | 43.01251
| 0
|
NCT00113399
|
[
4
] | 1,052
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This is a world wide study to evaluate the remission and joint damage in subjects treated with abatacept in addition to methotrexate versus subjects who receive methotrexate along with a placebo.
| null |
Rheumatoid Arthritis
|
abatacept, methotrexate, erosive RA
| null | 2
|
arm 1: abatacept 10 mg/kg intravenous (IV) + methotrexate arm 2: placebo IV + methotrexate
|
[
1,
1
] | 3
|
[
0,
0,
0
] |
intervention 1: abatacept 10 mg/kg IV monthly, methotrexate weekly, for 24 months intervention 2: placebo IV, monthly, methotrexate weekly for 12 months followed by abatacept 10 mg/kg IV monthly, methotrexate weekly for 12 months intervention 3: Oral, titrated to at least 15 mg per week not to exceed 20 mg per week administered every 28 days from Month 12 to Month 24
|
intervention 1: Abatacept intervention 2: placebo intervention 3: methotrexate
| 89
|
Huntsville | Alabama | United States | -86.58594 | 34.7304
Huntington Beach | California | United States | -117.99923 | 33.6603
Colorado Springs | Colorado | United States | -104.82136 | 38.83388
Trumbull | Connecticut | United States | -73.20067 | 41.24287
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Cumberland | Maryland | United States | -78.76252 | 39.65287
Hagerstown | Maryland | United States | -77.71999 | 39.64176
Lincoln | Nebraska | United States | -96.66696 | 40.8
Binghamton | New York | United States | -75.91797 | 42.09869
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Greenville | North Carolina | United States | -77.36635 | 35.61266
Statesville | North Carolina | United States | -80.8873 | 35.78264
Norman | Oklahoma | United States | -97.43948 | 35.22257
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Duncansville | Pennsylvania | United States | -78.4339 | 40.42341
Charleston | South Carolina | United States | -79.93275 | 32.77632
Austin | Texas | United States | -97.74306 | 30.26715
Arlington | Virginia | United States | -77.10428 | 38.88101
Malvern | Victoria | Australia | 145.02811 | -37.86259
Shenton Park | Western Australia | Australia | 115.79807 | -31.95575
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Hasselt | N/A | Belgium | 5.33781 | 50.93106
Leuven | N/A | Belgium | 4.70093 | 50.87959
Goiânia | Goiás | Brazil | -49.25389 | -16.67861
Curitiba | Paraná | Brazil | -49.27306 | -25.42778
Rio de Janeiro - Rj | Rio de Janeiro | Brazil | N/A | N/A
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
St. John's | Newfoundland and Labrador | Canada | -52.70931 | 47.56494
Kitchener | Ontario | Canada | -80.5112 | 43.42537
Toronto | Ontario | Canada | -79.39864 | 43.70643
Montreal | Quebec | Canada | -73.58781 | 45.50884
Québec | Quebec | Canada | -71.21454 | 46.81228
Sherbrooke | Quebec | Canada | -71.89908 | 45.40008
Saskatoon | Saskatchewan | Canada | -106.66892 | 52.13238
Prague | N/A | Czechia | 14.42076 | 50.08804
Dijon | N/A | France | 5.01667 | 47.31667
Montpellier | N/A | France | 3.87635 | 43.61093
Nice | N/A | France | 7.26608 | 43.70313
Strasbourg | N/A | France | 7.74553 | 48.58392
Berlin | N/A | Germany | 13.41053 | 52.52437
Hamburg | N/A | Germany | 9.99302 | 53.55073
Leipzig | N/A | Germany | 12.37129 | 51.33962
Leipzig | N/A | Germany | 12.37129 | 51.33962
Jesi(Ancona) | N/A | Italy | 13.24368 | 43.52142
Milan | N/A | Italy | 12.59836 | 42.78235
Chihuahua City | Chihuahua | Mexico | -106.08889 | 28.63528
León | Guanajuato | Mexico | -101.67374 | 21.12908
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
D.f. | Mexico City | Mexico | N/A | N/A
Morelia | Michioacan | Mexico | -101.18443 | 19.70078
Cuernavaca | Morelos | Mexico | -99.23075 | 18.9261
Monterrey | Nuevo León | Mexico | -100.31721 | 25.68435
San Luis Potosí City | San Luis Potosí | Mexico | -100.97135 | 22.15234
Metepec | State of Mexico | Mexico | -99.60175 | 19.25934
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Leiden | N/A | Netherlands | 4.49306 | 52.15833
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
Poznan | N/A | Poland | 16.92993 | 52.40692
Poznan | N/A | Poland | 16.92993 | 52.40692
Warsaw | N/A | Poland | 21.01178 | 52.22977
Ponce | N/A | Puerto Rico | -66.62398 | 18.01031
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Bloemfontein | Free State | South Africa | 26.214 | -29.12107
Muckleneuk | Gauteng | South Africa | N/A | N/A
Pretoria | Gauteng | South Africa | 28.18783 | -25.74486
Berea | KwaZulu-Natal | South Africa | 30.99337 | -29.85185
Panorama | Western Cape | South Africa | N/A | N/A
Anyang | N/A | South Korea | 127.1464 | 36.9577
Daegu | N/A | South Korea | 128.59111 | 35.87028
Daejeon | N/A | South Korea | 127.38493 | 36.34913
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
A Coruña | N/A | Spain | -8.396 | 43.37135
Santander | N/A | Spain | -3.80444 | 43.46472
Seville | N/A | Spain | -5.97317 | 37.38283
Manchester | Greater Manchester | United Kingdom | -2.23743 | 53.48095
Glasgow | Lanarkshire | United Kingdom | -4.25763 | 55.86515
Leeds | North Yorkshire | United Kingdom | -1.54785 | 53.79648
Newcastle | Northumberland | United Kingdom | -5.88979 | 54.21804
| 0
|
NCT00122382
|
[
3
] | 62
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 1FEMALE
| true
|
Study Design: This ia a Phase II study.
Subjects: Patients with chemotherapy naive epithelial ovarian cancer; or fallopian, primary peritoneal and papillary serous mullerian tumors will be recruited.
Carboplatin and Taxol (paclitaxel) will be administered concurrently with bevacizumab after surgery for 6-8 cycles every 21 (q21) days. Bevacizumab will be omitted in the first cycle, immediately post-operatively. This will be followed by one year of bevacizumab q21.
Outcomes: Outcomes include toxicity, response rate, and progression free survival.
|
Ovarian cancer is diagnosed in approximately 26,000 American women each year, and is the leading cause of death from gynecologic cancers. Difficult to detect, the disease typically presents only when advanced. Ovarian cancer is among the most sensitive of solid tumors to chemotherapy. However, the majority of patients with ovarian cancer who achieve a complete remission with first line platinum-based chemotherapy will ultimately develop recurrent disease. The combination of carboplatin and paclitaxel is the standard first line combination in the US.
In patients with advanced ovarian cancer, carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel. The randomized trial, GOG-158 finally confirmed the adoption of this standard with an improved toxicity profile of the combination of cisplatin and paclitaxel, a doublet that had been previously demonstrated to have a substantially better progression free and overall survival advantage compared with cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with good prognosis completely resected advanced disease.
In parallel European, multicentre, randomised trials, between January, 1996, and March, 2002, 802 patients with platinum-sensitive ovarian cancer relapsing after 6 months of being treatment-free were enrolled from 119 hospitals in five countries (ICON III). Patients were randomly assigned paclitaxel plus platinum chemotherapy or conventional platinum-based chemotherapy. Survival curves demonstrated a difference in favor of paclitaxel plus platinum (hazard ratio 0.82 \[95% CI 0.69-0.97\], p=0.02), corresponding to an absolute difference in 2-year survival of 7% between the paclitaxel and conventional treatment groups (57 vs 50% \[95% CI for difference 1-12\]), and median survival of 5 months (29 vs 24 months \[1-11\]).
Since the hypothesis of targeting angiogenesis to treat cancer was first described in 1971 by Judah Folkman, there has been intense research into the development of antiangiogenic cancer therapies. Tumors are dependent on their development of a vascular supply. Recent work has shown that, if cells are already transformed, angiogenesis can be initiated with a tumor mass comprising as few as 100-300 cells.
VEGF actions are mediated through binding to two receptor tyrosine kinases, VEGF-R-1 (Flt-1) and VEGF-R- 2 (KDR; whose murine form is known as Flk-1). Activation of these receptors by VEGF triggers the phosphorylation of a multitude of proteins that are active in signal transduction cascades. VEGF gene expression is upregulated by a wide range of stimuli including hypoxia, nitric oxide, estrogen, a variety of growth factors (e.g., FGF-4, PDGF, TNF, TGF-b, EGF, IL-6, IL-1b, #76) and common genetic events associated with the malignant phenotype (loss of tumor suppressor genes such as p53 and activation of oncogenes such as ras, v-src and HER2/neu). Beside major angiogenic properties, VEGF is a potent mitogen for vascular endothelium, inhibits endothelial apoptosis and mobilizes bone marrow-derived endothelial cell precursors. VEGF also mediates the secretion of enzymes involved in the degradation of extracellular matrix, modulates migration, increases vascular permeability, upregulates hexose transport and induces monocyte migration.
Ovarian cancers secrete large amounts of VEGF in vitro and in vivo, and VEGF appears to play a crucial role in angiogenesis and tumor induced immunosuppression in ovarian cancer patients. Indeed, VEGF has been confirmed as an independent prognostic indicator by multivariate analysis of survival.
Angiogenesis is crucial in the development of ovarian cancer. VEGF is closely linked to normal ovarian function and is required for the development of the corpus luteum and the maturation of the endometrium. Elevated VEGF expression occurs in all stages of ovarian cancer and is associated with poor prognosis. In fact, VEGF levels appear to be prognostically important. In addition to its role in ovarian-cancer-associated angiogenesis, VEGF overexpression is directly associated with the production of ascitic fluid, a feature probably related to its ability to induce endothelial hyperpermeability. In studies monitoring VEGF after tumor resection, VEGF appears to be a valid tumor marker, following a dramatic decline after surgery, the levels rise at recurrence.
The parent murine antibody of bevacizumab, A.4.6.1, demonstrated promising antitumor activity in a subcutaneous SKOV-3 human ovarian cancer xenograft model. Interestingly, in the intraperitoneal model of the same cell line, A.4.6.1 produced only partial inhibition of tumor growth, but was associated with almost complete inhibition of ascites production. These data provided the rationale for evaluation of bevacizumab in ovarian cancer. A Gynecologic Oncology Group (GOG) phase II study of bevacizumab monotherapy is ongoing, and a second trial will examine the combination of bevacizumab with daily, low-dose, oral cyclophosphamide, using metronomic dosing in the hope that 'less is more'.
Bevacizumab (rHumAb VEGF; Genentech, Inc., CA), a recombinant humanized monoclonal antibody directed to VEGF, and neutralizes the biological properties of human VEGF. Bevacizumab, derived from the murine antibody A.4.6.1, comprises 93% human IgG frameworks and 7% murine-derived antigen-binding regions, the humanization providing a longer half-life and less immunogenicity.
Based on preclinical data, a phase I/II program with bevacizumab was initiated. The initial phase I trial enrolled 25 patients in a dose-escalation fashion (0.1-10.0 mg/kg on days 0, 28, 35, and 42). No grade 3 or 4 toxicity was seen that was directly attributable to therapy. There were three episodes of tumor-related bleeding, including a hemorrhage in a previously undetected cerebral metastasis. Grade 1 and 2 toxicities, possibly or probably related to treatment, included asthenia, headache, and nausea. There were no complete or partial responses seen, although one patient with renal cell carcinoma achieved a mixed response.
The material use in this study is NOT commercially available Avastin™ (Genentech, Inc.; South San Francisco, CA), and may differ from that product.
Bevacizumab demonstrated preclinical and clinical activity in colorectal cancer and Genentech chose this as the disease for their registration studies. At ASCO 2003 Hurwitz et al reported the results of their phase III study of standard bolus irinotecan/5-FU/LV (IFL) plus bevacizumab (5 mg/kg). An impressive median survival advantage (20.3 months vs. 15.6 months \[p=0.00003\]) was reported in 925 patients receiving first line therapy with irinotecan, 5-fluorouracil, leucovorin treatment for metastatic colorectal cancer. Only grade 3 hypertension (11%), easily managed with oral medications, was clearly increased in this Phase III study. Gastrointestinal perforation, although rare, was possibly seen more frequently.
Importantly, this was the first phase III validation of an antiangiogenic approach for the treatment of human cancer. Several further, large phase III trials of bevacizumab in metastatic colorectal cancer are under way. These include a first-line study of standard 5-FU/LV with or without bevacizumab in patients who are not appropriate for irinotecan therapy. A further phase III study will assess the FOLFOX regimen with or without bevacizumab in the second-line setting for patients who have failed previous irinotecan plus 5-FU treatment. These results will help to define the benefit of anti-VEGF therapy.
Other studies are awaited, notably ECOG 4599 a randomized comparison of Taxol and carboplatin with and without bevacizumab, in patients with non-small cell lung cancer has completed accrual with over 600 patients.
There are three reasons to investigate protracted exposure to bevacizumab. Firstly, the agent, while inducing apoptosis, is considered a cytotoxic and protracted exposure is thought to be necessary to maintain tumor dormancy. Secondly, the studies in colorectal cancer treated patients until tumor progression. Lastly, there is an evolving paradigm in the treatment of ovarian cancer. It is now widely accepted that continual rather than intermittent palliative chemotherapy translates into a better quality of life. The Gynecologic Oncology Group have recently reported a provocative randomized controlled trial that confirmed a significant and large improvement in progression free survival (GOG 178), considered the most important end point in the patients with advanced ovarian cancer. Furthermore, in the preclinical studies of ovarian cancer, the ovarian cancer model presented a compelling argument for prolonged bevacizumab administration. Having inoculated the human ovarian carcinoma cell line SKOV-3 within the peritoneal cavity of immunodeficient mice, tumor engrafted in 7 to 10 days. The function-blocking VEGF antibody, A4.6.1 significantly inhibited subcutaneous SKOV-3 tumor growth approximately 20 fold compared with controls (P \< 0.05), and similarly in the intraperitoneal model. Importantly, within 2 to 3 weeks of cessation of A4.6.1 treatment, effectively treated mice developed severe ascites, became cachectic, and had to be killed, and subsequent tumor burden in these animals varied from moderate to high. It should be clarified that the murine study utilized A4.6.1 the murine precursor of bevacizumab, but that the results can be extrapolated to the actions of bevacizumab.
OVERVIEW OF TRIAL DESIGN Study Design: Open label phase II study. Subjects: Patients with chemotherapy naive epithelial ovarian cancer; or fallopian, primary peritoneal and papillary serous mullerian tumors .
CHEMOTHERAPY Carboplatin and paclitaxel administered concurrently with bevacizumab after surgery for for 6-8 cycles q21 days. Bevacizumab will be omitted in the first cycle, immediately post-operatively and continued for one year of consolidation therapy.
|
Ovarian Cancer
|
Carboplatin Paclitaxel Bevacizumab Ovarian Cancer
| null | 1
|
arm 1: Paclitaxel carboplatin bevacizumab
|
[
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Given intravenously intervention 2: Given intravenously intervention 3: Given intravenously
|
intervention 1: Paclitaxel intervention 2: Carboplatin intervention 3: Bevacizumab
| 0
| null | 0
|
NCT00129727
|
[
3
] | 211
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
Sodium nitroprusside (SNP) has been approved for control of blood pressure in adults, yet there are no controlled studies in children. The purpose of this study is to determine the efficacy and safety of sodium nitroprusside in children who will be having surgery, and who require blood pressure lowering in order to decrease the amount of blood loss during their surgery.
|
The trial is a multicenter randomized, double-blind, parallel group, dose-ranging, effect-controlled study examining the effects of sodium nitroprusside in pediatric subjects requiring relative hypotension during a surgical or medical procedure. The goal is to establish the starting and maximum infusion rates that afford optimum blood pressure control in children and a safe dosing regimen in children. The objective is to describe the relationship between the infusion rate of nitroprusside and changes in blood pressure.
The specific aims of this trial are:
1. To define the onset and offset of blood pressure lowering effects of nitroprusside to obtain adequate instructions for dose titration in the pediatric population.
2. To construct a dose-response model that defines the relationship between nitroprusside infusion rate and changes in blood pressure in pediatric subjects.
3. To assess the safety of nitroprusside administration in pediatric subjects requiring controlled reduction of blood pressure.
|
Hypotension
|
children sodium nitroprusside controlled hypotension dose-response pharmacokinetics pharmacodynamics safety efficacy
| null | 4
|
arm 1: Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons. arm 2: Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons. arm 3: Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons arm 4: Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons
|
[
1,
1,
1,
1
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS (Interactive Voice Response System). intervention 2: Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS. intervention 3: Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS. intervention 4: Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS
|
intervention 1: Nitroprusside intervention 2: Nitroprusside intervention 3: Nitroprusside intervention 4: Nitroprusside
| 1
|
Stanford | California | United States | -122.16608 | 37.42411
| 0
|
NCT00135668
|
[
3
] | 34
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The purpose of this study is to determine the effectiveness of etanercept in the treatment of patients with sub-acute lung injury following a bone marrow transplant. This study will also examine the toxicity of treatment with etanercept as well as whether there is an improved quality of life in these patients.
|
Lung or breathing problems can develop several months to years following a bone marrow transplant. In some cases, these breathing problems develop without any signs of germs or infection in the lungs. The name for this type of breathing problem is called "Sub-Acute Lung Injury". Sub-acute lung injury often develops many months, even years following a bone marrow transplant. It is often characterized by shortness of breath, cough, wheezing and fatigue.
Sub-acute lung injury can either lead to the formation of scar tissue in the lungs (making it difficult to take deep breaths), or it can cause the lungs to get weak (making people feel out of breath easily). Approximately 25 - 50% of patients with sub-acute lung injury may eventually die from the damage in their lungs. Typically, such patients die from infections that develop inside the damaged lungs.
In this study, treatment with an experimental drug called Etanercept will be used. (Enbrel). The physicians feel there is the possibility that Etanercept may help improve breathing. Breathing ability will be assessed prior to treatment as well as during and after treatment so that comparisons can be made.
|
Lung Injury, Acute Respiratory Distress Syndrome, Adult Bronchiolitis Obliterans
|
Enbrel Stem Cell Transplantation Lung Injury
| null | 1
|
arm 1: Etanercept for lung injury
|
[
0
] | 1
|
[
0
] |
intervention 1: Etanercept will be given on an open label, single arm basis to patients with non-infectious, sub-acute lung injury. 0.4 mg/kg/dose to a maximum of 25 mg, subcutaneously, twice weekly, for a total of 24 dosages.
|
intervention 1: Etanercept
| 1
|
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
| 0
|
NCT00141726
|
[
0
] | 15
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
Malignant infantile osteopetrosis (MIOP) is a rare fatal genetic disorder that is characterized by the bone's inability to regulate remodeling. The only curative therapy is hematopoietic stem cell transplantation. Stem cells provided from an HLA identical matched sibling donor is the standard of care, but not feasible for the majority of patients. In addition, due to the potentially rapid progression of this disease, the time to identify a suitable HLA matched unrelated donor is not optimal. Therefore this study is designed to test the hypothesis that children with osteopetrosis can properly engraft hematopoietic stem cells that are donated from a partially matched parental donor, or "haploidentical" stem cell donor that are processed on the investigational device, CliniMACS selection system.
|
The primary objective of this trial will be answered strictly by those patients enrolled who receive a haploidentical stem cell donor graft.
Patients with a matched sibling donor will be offered participation in this clinical trial and will receive a standard myeloablative conditioning regimen followed by the infusion of an unmanipulated bone marrow graft. However, data from these transplant recipients will be reported in a descriptive manner only.
Secondary Objectives in this trial include the following:
* To describe the outcome of children with MIOP who receive hematopoietic stem cells from a matched sibling donor or a haploidentical donor utilizing a uniform approach one year from transplant
* To estimate the fraction of children with MIOP who have a genetic defect correlating to the osteopetrosis phenotype
* To assess carrier-state of the genetic mutation in parents with an affected child
* To assess carrier-state of the genetic mutation in siblings of affected children
* To estimate the effect of age at the time of hematopoietic stem cell transplantation on the overall outcome of children with MIOP
* To describe the kinetics of select cytokine expression before and after transplantation
|
Osteopetrosis
|
Osteopetrosis Autosomal recessive bone disease Haploidentical stem cell transplantation Allogeneic stem cell transplantation T-cell depletion methodology Miltenyi Biotec CliniMACS stem cell selection device
| null | 1
|
arm 1: None
|
[
5
] | 3
|
[
3,
1,
0
] |
intervention 1: An infusion of HLA partially matched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device. intervention 2: Stem cell selection device intervention 3: Haploidentical stem cell transplant recipients will receive a reduced intensity conditioning regimen consisting of OKT-3, Fludarabine, Thiotepa , and Melphalan followed by an infusion of a T-cell depleted donor stem cell product. Rituximab will be administered within 24 hours of the infusion in an effort to prevent post transplantation lymphoproliferative disorders (PTLPD). In addition to T-cell depletion of the donor product, cyclosporine will be provided as prophylaxis for (GVHD)Graft versus Host Disease
Recipients of a matched sibling donor product will receive a myeloablative conditioning regimen consisting of busulfan and cyclophosphamide. Cyclosporine will be administered for GVHD prophylaxis.
|
intervention 1: Stem Cell Transplantation intervention 2: Miltenyi Biotec CliniMACS intervention 3: Systemic chemotherapy and antibodies
| 1
|
Memphis | Tennessee | United States | -90.04898 | 35.14953
| 0
|
NCT00145587
|
[
5
] | 76
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.
|
A significant number of schizophrenics exhibit partial or no response to typical antipsychotic medications. Clozapine has been shown to be more effective in treating schizophrenia than typical antipsychotic drugs. However, only an estimated 30% to 60% of people who are unresponsive to treatment with typical antipsychotics will respond to treatment with clozapine. Taking clozapine with pimozide, an antipsychotic drug, can increase clozapine's effects. However, sufficient research on this approach has not yet been performed. This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.
Participants in this double-blind study will receive a stable dose of clozapine for eight weeks prior to enrollment. For the first 4 weeks following enrollment, baseline measurements will be taken. Once a week, participants will report to the study site, where symptom severity, cognitive ability, and functional status, including reading level, will be assessed. In addition, participants will receive a standard medical examination, which will include blood tests and an EKG. Upon completion of this initial phase, participants will be randomly assigned to one of two treatment groups: clozapine combined with pimozide; or clozapine combined with placebo. This phase will last for 12 weeks. Study visits will continue to occur weekly, and will be used to re-assess the measurements obtained during baseline. In addition, participants will have an EKG at each study visit for the first 4 weeks of treatment. All baseline measurements will be repeated in Week 12.
|
Schizophrenia Psychotic Disorders
|
Schizophrenia Clozapine Treatment Combination Unresponsive Schizoaffective Disorders
| null | 2
|
arm 1: Participants will receive encapsulated placebo made to match active drug arm 2: Participants will receive pimozide flexible dosing
|
[
2,
0
] | 2
|
[
0,
0
] |
intervention 1: Each capsule of active treatment will contain 2 mg of pimozide. Dosing will be flexible and will range from a minimum of 2 mg per day to 8 mg per day. Dosing will begin at Week 1 with 1 capsule per day. This will be slowly titrated at a rate of 1 capsule per week to a maximum of 4 capsules depending upon clinical response and side effects. intervention 2: Active drug and placebo will be encapsulated in an identical fashion. The placebo capsule will be made to match in appearance and weight. There will be flexible dosing, allowing a minimum of 1 capsule per day to 4 capsules per day, in order to match the dosing range of the active treatment.
|
intervention 1: Pimozide intervention 2: Placebo
| 3
|
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
W. Brentwood | New York | United States | N/A | N/A
| 0
|
NCT00158223
|
[
5
] | 240
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 1FEMALE
| false
|
To evaluate the efficacy and safety of 300 mg and 400 mg doses of PROMETRIUM® capsules in women of reproductive age with secondary amenorrhea
| null |
Secondary Amenorrhea
|
To collect additional data on 300 and 400 mg doses of PROMETRIUM in women with secondary amenorrhea
| null | 2
|
arm 1: None arm 2: None
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: 300 mg (3x100mg capsules) by mouth once daily at bedtime for 10 days X 3 cycles intervention 2: 400 mg (4x100mg capsules) by mouth once daily at bedtime for 10 days X 3 cycles
|
intervention 1: PROMETRIUM® 300 mg intervention 2: PROMETRIUM® 400 mg
| 42
|
Mobile | Alabama | United States | -88.04305 | 30.69436
Montgomery | Alabama | United States | -86.29997 | 32.36681
Tucson | Arizona | United States | -110.92648 | 32.22174
Jonesboro | Arkansas | United States | -90.70428 | 35.8423
Carmichael | California | United States | -121.32828 | 38.61713
Encinitas | California | United States | -117.29198 | 33.03699
San Diego | California | United States | -117.16472 | 32.71571
Avon | Connecticut | United States | -72.83065 | 41.80982
Groton | Connecticut | United States | -72.07841 | 41.3501
New Britian | Connecticut | United States | N/A | N/A
Waterbury | Connecticut | United States | -73.0515 | 41.55815
West Hartford | Connecticut | United States | -72.74204 | 41.76204
Aventura | Florida | United States | -80.13921 | 25.95648
Clearwater | Florida | United States | -82.8001 | 27.96585
West Palm Beach | Florida | United States | -80.05337 | 26.71534
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Atlanta | Georgia | United States | -84.38798 | 33.749
Powder Springs | Georgia | United States | -84.68382 | 33.85955
Champaign | Illinois | United States | -88.24338 | 40.11642
Chicago | Illinois | United States | -87.65005 | 41.85003
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
Baltimore | Maryland | United States | -76.61219 | 39.29038
St Louis | Missouri | United States | -90.19789 | 38.62727
Reno | Nevada | United States | -119.8138 | 39.52963
New York | New York | United States | -74.00597 | 40.71427
New Bern | North Carolina | United States | -77.04411 | 35.10849
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Erie | Pennsylvania | United States | -80.08506 | 42.12922
Hershey | Pennsylvania | United States | -76.65025 | 40.28592
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pottstown | Pennsylvania | United States | -75.64963 | 40.24537
Greenville | South Carolina | United States | -82.39401 | 34.85262
Conroe | Texas | United States | -95.45605 | 30.31188
Corpus Christi | Texas | United States | -97.39638 | 27.80058
Houston | Texas | United States | -95.36327 | 29.76328
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Norfolk | Virginia | United States | -76.28522 | 36.84681
Seattle | Washington | United States | -122.33207 | 47.60621
| 0
|
NCT00160199
|
[
3
] | 64
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
To assess the 2 year survival of patients with Stage III unresectable non-small cell lung cancer receiving consolidation gemcitabine or gemcitabine plus docetaxel following concurrent chemotherapy and radiation.
| null |
Non-small Cell Lung Cancer
| null | 2
|
arm 1: None arm 2: None
|
[
0,
0
] | 5
|
[
0,
0,
0,
0,
4
] |
intervention 1: After induction chemotherapy, radiation therapy and 10 weeks with no disease progression, randomized consolidation treatment begins. In both treatment arms, gemcitabine 1000 milligrams per meter squared (mg/m2), is administered intravenously (IV), on days 1 and 8 of every 21-day cycle for 3 cycles. intervention 2: Following cisplatin-etoposide induction chemotherapy, radiation therapy and 10 weeks with no disease progression, randomized consolidation treatment begins. In this treatment arm, docetaxel 75 mg/m2, is administered IV on day 1 of each 21-day cycle for 3 cycles. Docetaxel is given after gemcitabine. intervention 3: As part of induction chemotherapy, cisplatin is given 50 mg/m2, IV, day 1, 8, 29 and 36 (spans 2 cycles) intervention 4: As part of induction chemotherapy, etoposide is given 50 mg/m2, IV, days 1-5 and 29-33 (spans 2 cycles) intervention 5: In conjunction with induction chemotherapy, radiation therapy is administered at a dose of 200 centi Gray (cGy) per day, Monday through Friday for 6 weeks
|
intervention 1: gemcitabine intervention 2: docetaxel intervention 3: cisplatin intervention 4: etoposide intervention 5: radiation therapy
| 15
|
Denver | Colorado | United States | -104.9847 | 39.73915
South Bend | Indiana | United States | -86.25001 | 41.68338
Baltimore | Maryland | United States | -76.61219 | 39.29038
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Kansas City | Missouri | United States | -94.57857 | 39.09973
St Louis | Missouri | United States | -90.19789 | 38.62727
Cleveland | Ohio | United States | -81.69541 | 41.4995
Portland | Oregon | United States | -122.67621 | 45.52345
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Memphis | Tennessee | United States | -90.04898 | 35.14953
Rosario | N/A | Argentina | -60.63932 | -32.94682
Beijing | N/A | China | 116.39723 | 39.9075
Chengdu | N/A | China | 104.06667 | 30.66667
Seoul | N/A | South Korea | 126.9784 | 37.566
Suwon | N/A | South Korea | 127.00889 | 37.29111
| 0
|
NCT00191139
|
|
[
0
] | 24
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The majority of kidney stones are treated with shock wave lithotripsy (SWL). We are examining if the medication Flomax will result in improved stone passage rates following SWL.
|
Placebo blinded study examining the effects of Flomax on stone passage rates following SWL.
|
Urolithiasis
|
urolithiasis
| null | 2
|
arm 1: Patients on this arm will be given 0.4mg of Flomax to be taken for one month following their shock wave lithotripsy procedure. arm 2: Patients on this arm will be given a sugar pill to be taken for one month following their shock wave lithotripsy procedure.
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: 0.4mg Flomax pills will be given to patients to take once daily for one month following shock wave lithotripsy to aid the stone passage. intervention 2: Comparable sugar pills will be given to the placebo group to take daily for one month following shock wave lithotripsy to aid stone passage.
|
intervention 1: Flomax intervention 2: Sugar pill
| 1
|
Atlanta | Georgia | United States | -84.38798 | 33.749
| 0
|
NCT00209131
|
[
2,
3
] | 23
|
RANDOMIZED
|
SEQUENTIAL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The objectives of this study are to:
1. To assess dose-limiting toxicities (DLTs) of capecitabine +/- oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
2. To determine the maximum-tolerated dose (MTD) when capecitabine
* oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
3. To determine the pathologic response rate of cetuximab +/- oxaliplatin in combination with capecitabine and radiotherapy (Phase 2)
|
Part of the treatment plan for this study is surgical removal of the tumor that is planned to occur 6 to 8 weeks after completion of radiotherapy (XRT). This study consists of 2 distinct phases (Phase 1 and Phase 2).
In Phase 1, the objectives are to
1. Assess dose-limiting toxicities (DLTs) and
2. Determine a maximum-tolerated dose (MTD)
The Phase 1 endpoints are assessed on an initial cohort of patients after the completion of the chemo-radiotherapy regimen at defined timepoints that precede surgery.
Phase 2 is the efficacy assessment portion of this study. In Phase 2, the objective is to accrue an expansion cohort. Efficacy assessments for phase 2 are to be assessed across all study participants at the time of, or after, surgery, as measured by the pathologic response rate; downstaging; and survival at 5 years from the start of treatment.
|
Rectal Cancer Colo-rectal Cancer
| null | 4
|
arm 1: * Cetuximab 250 mg/m² / week
* Capecitabine 800 mg/m²
* Radiotherapy (XRT)
* Oxaliplatin 100 mg/m², Days 2 and 23 arm 2: * Cetuximab 250 mg/m² / week
* Capecitabine 700 mg/m²
* Radiotherapy (XRT)
* Oxaliplatin 85 mg/m², Days 2 and 23 arm 3: * Cetuximab 250 mg/m² / week
* Capecitabine 800 mg/m²
* Radiotherapy (XRT) arm 4: * Cetuximab 250 mg/m² / week
* Capecitabine 1000 mg/m²
* Radiotherapy (XRT)
|
[
0,
0,
0,
0
] | 5
|
[
0,
0,
0,
4,
0
] |
intervention 1: Cetuximab is a chimeric anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, administered via a intravenous (IV) infusion at 400 mg/m² (initial loading dose) or 250 mg/m² (weekly dose). Dosage is based on m² of body surface area (BSA) intervention 2: Oxaliplatin is a cancer medication used to treat colorectal cancer, and is administered on Days 2 and 23. intervention 3: Capecitabine is a cancer medication, and is administered based on m² of body surface area (BSA) delivered in equivalent morning and evening doses intervention 4: Radiotherapy is administered on weekdays in 180 centigray fractions ("doses"), for 28 total fractions delivering a total dose of 5040 centigray (cGy) intervention 5: Diphenhydramine HCl 50 mg (or equivalent) is administered as a per-medication for cetuximab
|
intervention 1: Cetuximab intervention 2: Oxaliplatin intervention 3: Capecitabine intervention 4: Radiotherapy intervention 5: Diphenhydramine hydrochloride (HCl)
| 1
|
Stanford | California | United States | -122.16608 | 37.42411
| 0
|
NCT00226941
|
|
[
5
] | 27
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
The goal of the investigators' study is to further understand the potentially beneficial effects of statin therapy in patients with heart failure. It is hypothesized that statins will 1) increase the heart's pumping ability 2) improve functioning of the sympathetic nervous system and 3) decrease immune activation in heart failure.
|
Recent evidence suggests that HMG-Coenzyme A (statin) therapy may be associated with improved survival in both ischemic and non-ischemic heart failure (HF). Large, randomized outcome studies of statins in HF are currently underway, but these trials will not address underlying mechanisms. The aim of the study is to investigate statins' potentially beneficial mechanisms of action in HF, focusing on: 1) sympathetic nervous system activation and 2) myocardial remodeling, and 3) immune activation in heart failure.
Fifty patients with systolic HF of non-ischemic etiology from a single center will be randomized in a double-blinded fashion to 3 months of atorvastatin 10mg QD (25 subjects) vs matching placebo QD (25 subjects). The following exams will be performed at baseline (pre-treatment) and at end of study (post-treatment): sympathetic microneurography, echocardiography, and peripheral blood chemokine analysis. Sympathetic microneurography at the peroneal nerve will directly quantify changes in sympathetic nerve activity (bursts/minute). Echocardiography (with the addition of MRI in a subset of subjects without pacemakers or implantable defibrillators) will be used to track changes in cardiac structure and function; indices of remodeling will include measurement of left ventricular mass index, left ventricular volume indices, left ventricular ejection fraction, and subendocardial scar quantification (MRI only). Immune activation will be characterized by circulating cytokines and chemokines. Additionally, quantification of established cardiac biomarkers (cardiac troponin, B-type natriuretic peptide, and C-reactive Protein), Holter monitor/heart rate variability studies, and quality of life and global clinical assessment will be performed pre- and post- treatment.
Neither sympathetic microneurography nor MRI have been previously utilized to assess statins' effects in humans with HF. The impact of statin therapy on inflammatory chemokine activation in HF also has not been studied. The knowledge gained from our proposed investigations may serve as a basis for understanding how statin therapy has potential to improve clinical outcomes in HF, and may ultimately lead to new therapeutic strategies for HF.
|
Heart Failure, Congestive
|
Randomized Controlled Trial Hydroxymethylglutaryl-CoA Reductase Inhibitors Sympathetic Nervous System Ventricular Remodeling Chemokines
| null | 2
|
arm 1: atorvastatin 10mg QD x 3 months arm 2: matched placebo QD x 3 months
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: atorvastatin 10mg PO QD intervention 2: matched placebo Qd x 3 months
|
intervention 1: atorvastatin intervention 2: placebo
| 1
|
Los Angeles | California | United States | -118.24368 | 34.05223
| 0
|
NCT00233480
|
[
3
] | 42
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX).
| null |
Rheumatoid Arthritis
|
Rituxan RA
| null | 2
|
arm 1: Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18).
Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion.
Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant).
Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk). arm 2: Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered.
Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion.
Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant).
Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
|
[
0,
0
] | 5
|
[
0,
0,
0,
0,
0
] |
intervention 1: Minimum of 1 mg/day oral (or folinic acid 5 mg/week) intervention 2: 15-25 mg/week oral or parenteral (10-14 mg/week if intolerant) intervention 3: 100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion) intervention 4: To maintain the blind, patients in Arm B (Rituximab 1000 mg) received placebo infusions at Months 6 and 18. intervention 5: 500 mg or 1000 mg IV\*2.
|
intervention 1: folate intervention 2: methotrexate intervention 3: methylprednisolone intervention 4: Placebo intervention 5: Rituximab
| 0
| null | 0
|
NCT00243412
|
[
2,
3
] | 144
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The purpose of this study is to evaluate the safety and effectiveness of the intetumumab, alone and in combination with dacarbazine, in patients with stage 4 melanoma.
|
This is a Phase 1/2, multi-center, randomized (the study medication is assigned by chance) study. This study will be conducted in 2 Phases (Phase 1 and Phase 2). Phase 1 of this study will be non-randomized, open-label (all people know the identity of the intervention) and dose-escalation phase. It includes screening period and treatment period, which consists of 2 parts (Part 1 and Part 2). In Part 1, participants will receive 1 of 3 single dose levels of intetumumab \[3 milligram per kilogram (mg/kg), 5 mg/kg or 10 mg/kg\]. Part 2 will include 2 dose cohorts: dacarbazine plus intetumumab (5 mg/kg) or dacarbazine plus intetumumab (10 mg/kg). Phase 2 of this study will be randomized, blinded (neither physician nor participant knows the intervention which the participant will receive) and controlled (an inactive substance and other medication is compared with a study medication to test whether the medication has a real effect in this clinical study). This phase of the study will include screening period, treatment period (8 cycles of treatment with every cycle once in 3 weeks) and follow-up period (24 weeks). During the treatment period, participants will be randomly assigned to 1 of 4 treatment groups, Group 1: dacarbazine plus placebo, Group 2: intetumumab (5 mg/kg), Group 3: intetumumab (10 mg/kg) and Group 4: dacarbazine plus intetumumab. Randomization will be further based on the site of metastases and Eastern Cooperative Oncology Group performance status at Baseline. Single-medication intetumumab treatment groups will be open-label, while the dacarbazine plus intetumumab or placebo groups will be blinded. The total duration of the Phase 2 of this study will be up to 52 weeks or up to 76 weeks in case of extended dosing (extended administrations \[up to 8 additional cycles\] of the same assigned treatment will be allowed for participants that are responding to therapy with stable disease or better). Participants will be assessed for incidence of dose limiting toxicities, pharmacokinetics and tumor responses. Participants' safety will be monitored throughout the study.
|
Melanoma
|
Melanoma Neoplasm CNTO 95 Dacarbazine Intetumumab
| null | 9
|
arm 1: Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation is not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab will be discontinued in Part 1 and participants will be treated at the highest, documented safe dose level at which receptor saturation is observed. arm 2: Intetumumab will be administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs. If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation is not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab will be discontinued in Part 1 and participants will be treated at the highest, documented safe dose level at which receptor saturation is observed. arm 3: Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs. arm 4: Intetumumab will be administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with stable disease (SD) or better, they will be considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine will be administered at the dose of 1000 milligram per meter-square (mg/m\^2) intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion. arm 5: Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they will be considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine will be administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion. arm 6: Placebo will be administered intravenously over a period of 2 hr (±15 minutes). Commercially available dacarbazine will be administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue with 10 mg/kg intetumumab alone. arm 7: Intetumumab will be administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they are considered eligible to receive up to 8 cycles of extended administrations. arm 8: Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they are considered eligible to receive up to 8 cycles of extended administrations. arm 9: Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they are considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine will be administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.
|
[
0,
0,
0,
0,
0,
0,
0,
0,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations. intervention 2: Commercially available dacarbazine will be administered intravenously over a 60-minute period (+30 minutes/-30 minutes) and prior to the intetumumab/placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue on intetumumab alone. intervention 3: Placebo will be administered intravenously over a period of 2 hours (+15 minutes/-15 minutes).
|
intervention 1: Intetumumab intervention 2: Dacarbazine intervention 3: Placebo
| 32
|
Scottsdale | Arizona | United States | -111.89903 | 33.50921
La Jolla | California | United States | -117.2742 | 32.84727
Santa Monica | California | United States | -118.49138 | 34.01949
Walnut Creek | California | United States | -122.06496 | 37.90631
Aurora | Colorado | United States | -104.83192 | 39.72943
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Miami | Florida | United States | -80.19366 | 25.77427
Atlanta | Georgia | United States | -84.38798 | 33.749
Park Ridge | Illinois | United States | -87.84062 | 42.01114
Beech Grove | Indiana | United States | -86.08998 | 39.72199
Omaha | Nebraska | United States | -95.94043 | 41.25626
Buffalo | New York | United States | -78.87837 | 42.88645
New York | New York | United States | -74.00597 | 40.71427
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Nashville | Tennessee | United States | -86.78444 | 36.16589
Dallas | Texas | United States | -96.80667 | 32.78306
Seattle | Washington | United States | -122.33207 | 47.60621
Berlin | N/A | Germany | 13.41053 | 52.52437
Bonn | N/A | Germany | 7.09549 | 50.73438
Buxtehude | N/A | Germany | 9.68636 | 53.46716
Düsseldorf | N/A | Germany | 6.77616 | 51.22172
Essen | N/A | Germany | 7.01228 | 51.45657
Hanover | N/A | Germany | 9.73322 | 52.37052
Jena | N/A | Germany | 11.5899 | 50.92878
Kiel | N/A | Germany | 10.13489 | 54.32133
Mannheim | N/A | Germany | 8.46694 | 49.4891
Münster | N/A | Germany | 7.62571 | 51.96236
Cambridge | N/A | United Kingdom | 0.11667 | 52.2
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Sheffield | N/A | United Kingdom | -1.4659 | 53.38297
Southampton | N/A | United Kingdom | -1.40428 | 50.90395
| 0
|
NCT00246012
|
[
3
] | 37
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The study will consist of two parts. In Part 1 the study will start enrolling 38 patients and then further 25 patients up to a total of 63 eligible patients. If the study gives good results it can be expanded to a total of 160 patients. SU011248 will be administered orally daily for 4 weeks followed by a 2-week rest at a starting dose of 50 mg \[milligrams\] with provision for dose reduction based on tolerability. All patients will receive repeated cycles of SU011248 until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival
| null |
Liver Neoplasms Unresectable Hepatocellular Carcinoma
|
Liver neoplasms, sunitinib, Phase 2
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: Sunitinib 50 mg by oral capsule, daily for 4 weeks in every 6 week cycle until progression or unacceptable toxicity.
|
intervention 1: Sunitinib (SU011248)
| 8
|
Clichy | N/A | France | 2.30952 | 48.90018
Rennes | N/A | France | -1.67429 | 48.11198
Saint Herrblain Cedex | N/A | France | N/A | N/A
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Taipei | N/A | Taiwan | 121.52639 | 25.05306
| 0
|
NCT00247676
|
[
3
] | 23
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The purpose of this study is to find out if the combination of bortezomib (Velcade), dexamethasone (Decadron) and rituximab (Rituxan) is effective in treating Waldenstrom's macroglobulinemia.
|
* This is an open-label study which means both the patient and the doctor will know what drugs and doses the patient is receiving throughout the study.
* Patients will receive 8 cycles of study treatment with bortezomib, dexamethasone and rituximab. Each cycle is 21 days long. Therapy is given on the first, fourth, eighth and eleventh day of each cycle, followed by a 10 day rest period. The first 4 cycles will be given one after the other. Three months after completing the fourth cycle of therapy, patients will receive one cycle of therapy every three months for a total of four more cycles.
* On the first, fourth, eighth and eleventh day of each cycle, the patient will receive bortezomib and dexamethasone as an intravenous injection through a needle in your vein. On the eleventh day only, the patient will also receive rituximab as an intravenous infusion after getting bortezomib and dexamethasone.
* Prior to each infusion of rituximab therapy, the patient will be asked to take some medications to prevent or reduce side effects of rituximab. These medications are benadryl, tylenol, and possibly more steroids. The doctor will determine which of these drugs are appropriate for the individual patient.
* During the rituximab infusion, the patients blood pressure and pulse will be monitored frequently and the infusion rate may be decreased depending upon the side effects experienced.
* After therapy is completed, the patient will be followed every three months for 2 more years for office visits and laboratory tests to determine how well they are doing and if the therapy continues to benefit them.
|
Waldenstrom's Macroglobulinemia
|
bortezomib dexamethasone rituximab
| null | 1
|
arm 1: A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
|
[
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles intervention 2: Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles intervention 3: Given intravenously after bortezomib and dexamethasone on day 11 of a 21-day cycle for 8 cycles
|
intervention 1: Bortezomib intervention 2: Dexamethasone intervention 3: Rituximab
| 2
|
Boston | Massachusetts | United States | -71.05977 | 42.35843
Boston | Massachusetts | United States | -71.05977 | 42.35843
| 0
|
NCT00250926
|
[
3
] | 51
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
To determine the objective tumor response of single-agent SU011248 at a dose of 50 mg orally once daily for 4 consecutive weeks and 2 weeks rest, repeated every 6 weeks in patients with metastatic Renal Cell Cancer (RCC).
| null |
Carcinoma, Renal Cell
|
Ph2, RCC, SU011248, SUNITINIB
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: 50mg, PO on day 28 of each 42 day cycle, until progression or unacceptable toxicity develops
|
intervention 1: SU011248 capsule
| 11
|
Akita | Akita | Japan | 140.11667 | 39.71667
Sapporo | Hokkaido | Japan | 141.35 | 43.06667
Tsukuba | Ibaragi | Japan | 140.11667 | 36.08333
Osaka | Osaka | Japan | 135.50107 | 34.69379
Sayama | Osaka | Japan | 135.56298 | 34.51685
Hamamatsu | Shizuoka | Japan | 137.73333 | 34.7
Sunto-gun | Shizuoka | Japan | N/A | N/A
Tokushima | Tokushima | Japan | 134.56667 | 34.06667
Chuo-ku | Tokyo | Japan | N/A | N/A
Yamagata | Yamagata | Japan | 140.36667 | 38.23333
Fukuoka | N/A | Japan | 130.41667 | 33.6
| 0
|
NCT00254540
|
[
3
] | 21
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
Purpose of this study:
There is some evidence that the best treatment for head and neck cancer involves a combination of radiation therapy and chemotherapy. Radiation therapy is a form of cancer treatment using high energy x-rays. Chemotherapy is a form of cancer treatment that uses special medications. This study uses two chemotherapy drugs (Taxol and Carboplatin), which are FDA approved for treating head and neck cancers. This treatment combination has been associated with difficulty, pain, or a burning sensation upon swallowing (called esophagitis), and decrease in blood cells (cells in the blood which fight against infection). The purpose of this study is to investigate whether the addition of another drug, Amifostine, can reduce the side effects of current combination treatment (radiation and chemotherapy which is standard of care). The addition of Amifostine is the investigational part of the study. The research study is also looking at the side effects of Amifostine and cancer's growth response to this combination treatment.
|
Patients presenting with locally advanced squamous cell carcinomas of head and neck (SCCHN) continue to represent a significant therapeutic challenge. The bulk of tumor burden often proves to be overwhelming for conventional radiotherapy. Attempts to improve upon these poor outcomes have led investigators to explore several new strategies, one such being chemoradiation. One of the trials conducted at the University of Maryland with carboplatin and paclitaxel with daily radiation showed 82% CR at the primary site. But the most commonly encountered grade 3 toxicities were mucositis (70%), leukopenia (30%) and 3% grade 4 leukopenia. Amifostine: An organic thiophosphate is radioprotective and has shown to protect experimental animals from lethal doses of radiation. Clinical trials have demonstrated that amifostine can provide protection against the hematological toxicities and mucositis seen with various chemotherapeutic agents. Theoretically, drug interactions between amifostine and chemotherapeutic agents are not likely to occur, due to amifostine¿s rapid clearance from plasma (90% of the drug is cleared within 6 minutes). A promising venue would be the investigation of amifostine¿s role in reducing the toxicities associated with chemoradiation (which is standard of care of treating squamous cell carcinomas of head and neck).
Principal objectives of the study: Primary: To evaluate whether the addition of the radioprotector amifostine can reduce the incidence and severity of mucositis and hematological toxicities caused by chemoradiation. Secondary: 1.To determine the toxicities of amifostine given in this setting. 2. To determine the response rate of this regimen in the population.
|
Head and Neck Cancer
|
Head and Neck cancer
| null | 1
|
arm 1: EVALUATION OF AMIFOSTINE FOR MUCOSAL AND HEMOPOETIC PROTECTION AND CARBOPLATIN, TAXOL, RADIOTHERAPY IN THE MANAGEMENT OF PATIENTS WITH HEAD AND NECK CANCER.
|
[
0
] | 4
|
[
0,
0,
0,
1
] |
intervention 1: Amifostine will be given at dose of 500 mg IV within one hour before radiation intervention 2: Carboplatin for 100 mg/m2 and will be administered after the taxol infusion intervention 3: Taxol will be given at a dose of 40 mg/m2 as a 3 hour infusion dose intervention 4: Radiation will be given at a dose of 1.8 Gy. for a total of 70.2 Gy
|
intervention 1: Amifostine intervention 2: Carboplatin intervention 3: Taxol intervention 4: Radiotherapy
| 1
|
Baltimore | Maryland | United States | -76.61219 | 39.29038
| 0
|
NCT00270790
|
[
3
] | 25
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
Phase 2 study, conducted in patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma undergoing high-dose chemotherapy and autologous stem cell transplantation.
|
This Phase 2 study will be conducted in patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma undergoing high-dose chemotherapy and autologous stem cell transplantation. Patients will be randomized to receive either LAD 11.25 mg 3 Month treatment or placebo and all patients will be vaccinated with KLH 6 months posttransplant. Patients will be evaluated to determine if the rate of immunologic recovery in the LAD group is enhanced compared with the placebo group.
|
Hodgkin Disease Lymphoma, Non-Hodgkin Multiple Myeloma Mantle Cell Lymphoma
|
Bone marrow transplantation Hematopoietic stem cell transplantation Hodgkin's disease non-Hodgkin's lymphoma multiple myeloma
| null | 2
|
arm 1: Three intramuscular injections LAD 11.25 mg 3 Month treatment administered approximately 3 months apart. arm 2: Three intramuscular injections of matched placebo administered approximately 3 months apart.
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: LAD intramuscular injection 11.25 mg, 3 month duration. To stimulate immune response, a subcutaneous key limpet hemocyanin (KLH) vaccination injection (1 mg) was administered at Month 6. intervention 2: Matched placebo intramuscular injection, 3 month duration. To stimulate immune response, a subcutaneous key limpet hemocyanin (KLH) vaccination injection (1 mg) was administered at Month 6.
|
intervention 1: Leuprolide acetate depot (LAD) 11.25 mg 3 Month intervention 2: Matched placebo
| 4
|
St Louis | Missouri | United States | -90.19789 | 38.62727
New York | New York | United States | -74.00597 | 40.71427
Durham | North Carolina | United States | -78.89862 | 35.99403
Houston | Texas | United States | -95.36327 | 29.76328
| 0
|
NCT00275262
|
[
3
] | 10
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
The purpose of this pilot is to initiate a program of research into the development of effective medication techniques to treat those children with ADHD who are referred because they are "partial" or "non-responders" to standard stimulant treatment.
|
We propose to do this with a single site, ten week, pilot study of 40 school age children, ages 6-17, with Attention-Deficit/ Hyperactivity Disorder (ADHD) and moderate or greater impairment (C-GAS \< 55) who show ADHD symptoms despite a trial in the community with their primary care practitioner with either of two of the most commonly used stimulants (i.e., either OROS-MPH (Concerta) or mixed salts of amphetamine (Adderall-XR)).
These children first will be classified into three groups: Group 1, those who had been treated with a maximal dose of stimulant with partial or no response; Group 2, those treated with a suboptimal dose of stimulant and showing partial or no response, and Group 3, those who developed side effects that limited continued treatment with optimal doses of a stimulant.
The next step will be to enter these children into an open, two week trial to confirm their treatment resistance. Group 2, those treated with suboptimal doses, will have the dosage increased to the maximum recommended stimulant dose. Group 1, those who had been treated for 4 weeks with maximal doses of a stimulant, or Group 3, those who developed moderate to severe drug-related side effects, will be switched to the other class of stimulant for a two week trial, unless they have been tried on both classes. Those children will be maintained on their current class of stimulant for two weeks. At the end of the two weeks, all children will be rated on the ADHD-IV-RS by the Study Doctor. Those who have shown moderate to severe side effects or those who respond will exit the trial and be treated openly. Children from Group 2 who continue to show no improvement after a week will switch to the other stimulant. All children from Group 2 tried on both stimulants and all children from Groups 1 and 3 who continue to show mean scores greater than 1 SD over the mean for age will be referred to Phase 2.
During phase 2, they will be randomized to one of two treatment arms for eight weeks. The first treatment arm, the "simple treatment" arm, will consist of parent training plus continued treatment with a stimulant that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response, plus a placebo matching aripiprazole. The second treatment arm, called the "combination" arm, will consist of parent training plus continued treatment on stimulant plus augmentation with a second generation antipsychotic (aripiprazole). Aripiprazole (Abilify™ ) is a product that is FDA-approved and marketed for the treatment of schizophrenia and for the treatment of acute manic episodes associated with Bipolar I Disorder in adults only. However, aripiprazole is also used to treat children and adolescents with aggressive and oppositional disorders in standard clinical practice. We will continue randomizing patients until we have 40 children with ADHD become eligible to enter Phase 2.
|
Attention Deficit Hyperactivity Disorder
|
Attention Deficit Hyperactivity Disorder ADHD Treatment resistant Partial responder Non-responder Atypical Antipsychotic
| null | 2
|
arm 1: This treatment arm (also called the "combination arm") consists of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus augmentation with aripiprazole. Aripiprazole pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Dosing will start at 2.5 mg and will be titrated up to 5 mg by week 1, and up to 10 mg by week 2 and for the remainder of the trial. arm 2: This treatment arm (also called the "simple treatment" arm) will consist of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus a placebo matching aripiprazole. Placebo pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis.
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: double blind capsules (abilify or placebo) taken once daily, up to 10mg. intervention 2: double blind capsules (abilify or placebo) taken once daily, up to 10mg.
|
intervention 1: aripiprazole intervention 2: Sugar pill
| 1
|
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT00279409
|
[
2
] | 6
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
This study examined the safety and potential efficacy of the monoclonal antibody efalizumab (Raptiva) for treating sight-threatening uveitis (eye inflammation). Efalizumab controls the activity of white blood cells called lymphocytes that cause inflammation. The drug is currently approved in the United States to treat patients with moderate to severe psoriasis.
Participants 18 and older with sight-threatening intermediate or posterior uveitis of at least 3 months duration, causing persistent macular edema in one or both eyes, were eligible for this study. The uveitis required treatment with at least 20 milligrams per day of prednisone, or the equivalent, or a combination of two or more anti-inflammatory treatments such as prednisone, methotrexate, cyclophosphamide, cyclosporine, etc.
Participants underwent the following tests and procedures:
* Medical history and physical examination.
* Weekly efalizumab treatment.
* Weekly eye examination, including measurement of vision and pressure in the eyes, dilation of the eyes and examination of the front and back parts of the eye.
* Weekly blood tests to measure the number and types of cells in the blood and to check for signs of inflammation and treatment side effects. At some visits, blood samples were collected to measure how much efalizumab remains in the blood and whether the body has developed an immune response to the medicine.
* Blood draw at enrollment and at 2 and 4 months for research tests to examine how participants' immune response was operating.
* Fluorescein angiography at enrollment and 1 and 3 months after enrollment, unless additional tests are needed, for medical management. This test checked for abnormalities of eye blood vessels. A yellow dye was injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina (the back portion of the eye) were taken with a special camera that flashes a blue light into the eye. The pictures show whether any dye has leaked from the vessels into the retina, indicating possible abnormalities.
* Monthly pregnancy test for women who could become pregnant.
Participants returned for treatment and clinic visits weekly for 16 weeks. After 16 weeks, participants whose macular edema had decreased and whose vision may have improved were offered to continue the injections.
|
Background: Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable.
Aims: This protocol evaluated the safety and potential efficacy of subcutaneous (SC) efalizumab (anti-CD11a) treatments for uveitis while reducing or eliminating standard medications commensurate with the standard of care. If the therapeutic benefit was sustained using the SC formulation, then maintenance therapy was continued as clinically indicated.
Methods: This was an open-label, non-randomized, clinical pilot study.
|
Uveitis Macular Edema
|
OCT Retinal Disease Adhesion Molecule Ocular Inflammation Raptiva Macular Edema Uveitis Immunosuppression
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: Participants who qualified for the study received weekly subcutaneous treatments of efalizumab, with the first dose being a test dose of 0.7 mg/kg and subsequent doses of 1 mg/kg (not to exceed 200 mg per dose), for a total treatment duration of 16 weeks.
|
intervention 1: Efalizumab
| 1
|
Bethesda | Maryland | United States | -77.10026 | 38.98067
| 0
|
NCT00280826
|
[
3
] | 21
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 1SINGLE
| false
| 1FEMALE
| true
|
Decreased bone strength is a serious medical problem present in many women with Anorexia Nervosa, or disordered eating. Women with weaker bones are more likely to suffer broken bones than women with normal bone strength.
We are investigating whether a hormone that is naturally produced by the human body, called growth hormone, can help strengthen the bones of women with this type of disordered eating.
|
* Twelve week study
* Eight visits, six of which can be conducted at your home physician's office
* Two bone density scans
* Hormonal and nutritional evaluations
|
Anorexia Nervosa Osteopenia Osteoporosis Eating Disorders
|
Anorexia Nervosa Eating disorder Bone Growth hormone Osteopenia Osteoporosis
| null | 2
|
arm 1: Treatment with rHGH arm 2: Treatment with Placebo
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: Dosage increased in steps for first four weeks. Self injection qd x 12 weeks intervention 2: Administered as Arm 1, rHGH active Injection qd x 12 weeks Dosage increase over four weeks
|
intervention 1: Recombinant Human Growth Hormone intervention 2: Placebo for Recombinant Human Growth Hormone
| 1
|
Boston | Massachusetts | United States | -71.05977 | 42.35843
| 0
|
NCT00283595
|
[
4
] | 489
|
RANDOMIZED
|
PARALLEL
| 1PREVENTION
| 0NONE
| false
| 0ALL
| true
|
Study is to compare antifungal prophylaxis of Voriconazole and Itraconazole in subjects who have had a Stem Cell Transplant. The success of the end point will be measured using evidence of Infection, drug compliance and survival.
| null |
Antifungal Prophylaxis of Invasive Fungal Infections
| null | 2
|
arm 1: None arm 2: None
|
[
1,
0
] | 2
|
[
0,
0
] |
intervention 1: Prophylaxis intervention 2: Prophylaxis
|
intervention 1: Itraconazole intervention 2: Vfend - voriconazole
| 49
|
Vancouver | British Columbia | Canada | -123.11934 | 49.24966
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Montreal | Quebec | Canada | -73.58781 | 45.50884
Bmo | N/A | Czechia | N/A | N/A
Prague | N/A | Czechia | 14.42076 | 50.08804
Cairo | N/A | Egypt | 31.24967 | 30.06263
Marseille | Cedex 09 | France | 5.38107 | 43.29695
Caen | N/A | France | -0.35912 | 49.18585
Créteil | N/A | France | 2.46569 | 48.79266
Paris | N/A | France | 2.3488 | 48.85341
Pessac | N/A | France | -0.6324 | 44.80565
Rouen | N/A | France | 1.09932 | 49.44313
Vandœuvre-lès-Nancy | N/A | France | 6.17114 | 48.66115
Villejuif | N/A | France | 2.35992 | 48.7939
Exohi Asvestohoriou | Thessaloniki | Greece | N/A | N/A
Athens | N/A | Greece | 23.72784 | 37.98376
Amman | N/A | Jordan | 35.94503 | 31.95522
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Porto | N/A | Portugal | -8.61099 | 41.14961
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Badalona | Barcelona | Spain | 2.24741 | 41.45004
Barcelona | Barcelona | Spain | 2.15899 | 41.38879
Barcelona | Barcelona | Spain | 2.15899 | 41.38879
Madrid | Madrid | Spain | -3.70256 | 40.4165
Madrid | Madrid | Spain | -3.70256 | 40.4165
Madrid | Madrid | Spain | -3.70256 | 40.4165
Salamanca | Salamanca | Spain | -5.66388 | 40.96882
Seville | Sevilla | Spain | -5.97317 | 37.38283
Valencia | Valencia | Spain | -0.37966 | 39.47391
Valencia | Valencia | Spain | -0.37966 | 39.47391
Ch-4031 Basel | N/A | Switzerland | N/A | N/A
Geneva | N/A | Switzerland | 6.14569 | 46.20222
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Kayseri | N/A | Turkey (Türkiye) | 35.48528 | 38.73222
Sutton | Surrey | United Kingdom | -0.2 | 51.35
Bristol | N/A | United Kingdom | -2.59665 | 51.45523
Cambridge | N/A | United Kingdom | 0.11667 | 52.2
Cardiff | N/A | United Kingdom | -3.18 | 51.48
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Leeds | N/A | United Kingdom | -1.54785 | 53.79648
Leicester | N/A | United Kingdom | -1.13169 | 52.6386
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
| 0
|
NCT00289991
|
|
[
2
] | 22
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 1FEMALE
| false
|
This study is to evaluate the safety of SU011248 (Sunitinib/Sutent) in combination with docetaxel in patients with metastatic or locally recurrent breast cancer who have not received chemotherapy treatment in the advanced disease setting.
| null |
Breast Neoplasms
|
advanced sunitinib (Sutent) docetaxel Phase 1B
| null | 1
|
arm 1: None
|
[
0
] | 2
|
[
0,
0
] |
intervention 1: Sunitinib (Sutent) 37.5 mg in schedule 2/1; Sunitinib (Sutent) 37.5 mg in continuous dosing (post discontinuation of axotere) and in accordance with Investigator decision intervention 2: Taxotere 75 mg/m2 iv, once every 3 weeks
|
intervention 1: Sunitinib (Sutent) intervention 2: Taxotere
| 3
|
Brussels | N/A | Belgium | 4.34878 | 50.85045
Milan | N/A | Italy | 12.59836 | 42.78235
Stockholm | N/A | Sweden | 18.06871 | 59.32938
| 0
|
NCT00291577
|
[
3
] | 21
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| true
| 0ALL
| false
|
Study investigating the use of pimecrolimus 1% cream for oral lichen planus
|
Lichen planus (LP) is an idiopathic inflammatory dermatosis of the skin and mucous membranes. Cutaneous lesions present as pink polygonal papules on the flexor wrists, trunk, thighs, shin and the dorsal hands. Oral lichen planus (OLP) represents a unique subset of LP and is often the sole manifestation of this disease. Clinically, the lesions can be reticulate, erythematous, atrophic or erosive, with the erosive form being the most common. Lesions can be found anywhere in the oral mucosa and are associated with burning pain which is worsened while eating. The risk of development of squamous cell carcinoma has been estimated to be as high as 5%. Treatments for oral lichen planus involve high potency topical steroid, systemic steroids, oral/topical retinoids and immunosuppressants. However, the long term side effects of steroids (e.g. striae, skin atrophy, telangiectasias, tachyphylaxis, secondary candidiasis and perioral dermatitis) prevent more extensive utilization except in the most severe cases. Given the debilitating nature of OLP, risk of malignant transformation, and long term side effects associated with current therapies, a safe intervention is needed for this disorder.
Tacrolimus and pimecrolimus may have fewer side affects than topical steroids. Recently, in an open label trial of 19 patients with recalcitrant erosive lichen planus, tacrolimus decreased the area of ulceration by 73% after an eight week course. Local irritation was the most common side effect. However, tacrolimus comes in an ointment base, a poorly tolerated vehicle for oral lesions. Topical treatment of oral lesions has also been compromised by problems with maintaining sufficient contact time between poorly adherent cream and ointment preparations and moist mucous membrane surfaces.
This study is designed to evaluate the topical application of pimecrolimus 1% cream when applied twice daily with occlusion in the treatment of oral lichen planus.
|
Oral Lichen Planus
|
oral lichen planus, pimecrolimus 1% cream
| null | 2
|
arm 1: "During the 6-week double-blind phase, all patients will be randomly assigned to receive either pimecrolimus 1% cream or its vehicle twice daily with occlusion on the affected areas. Topical application of pimecrolimus1% cream for oral erosive lichen planus for a duration of 6 weeks; ¼ gram of cream will be applied to each of the 2 sides of the mouth BID with a 2x2 gauze." arm 2: "During the 6-week double-blind phase, all patients will be randomly assigned to receive either pimecrolimus 1% cream or its vehicle twice daily with occlusion on the affected areas. Topical application of pimecrolimus1% cream for oral erosive lichen planus for a duration of 6 weeks; ¼ gram of cream will be applied to each of the 2 sides of the mouth BID with a 2x2 gauze."
|
[
1,
2
] | 1
|
[
0
] |
intervention 1: pimecrolimus cream or matching placebo BID for 6 weeks
|
intervention 1: Pimecrolimus 1% cream
| 1
|
Salt Lake City | Utah | United States | -111.89105 | 40.76078
| 0
|
NCT00297037
|
[
4
] | 926
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
A randomized controlled trial comparing safety and efficacy of carboplatin and paclitaxel plus or minus sorafenib in chemonaive patients with stage III-IV non-small cell lung cancer.
| null |
Carcinoma, Non-Small Cell Lung
|
Non-Small Cell Lung Cancer NSCLC
| null | 2
|
arm 1: Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle. arm 2: Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle. intervention 2: Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
|
intervention 1: Nexavar (Sorafenib, BAY43-9006) + carboplatin + paclitaxel intervention 2: Carboplatin plus Paclitaxel
| 202
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Mobile | Alabama | United States | -88.04305 | 30.69436
Tucson | Arizona | United States | -110.92648 | 32.22174
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Springdale | Arkansas | United States | -94.12881 | 36.18674
Anaheim | California | United States | -117.9145 | 33.83529
Beverly Hills | California | United States | -118.40036 | 34.07362
Burbank | California | United States | -118.30897 | 34.18084
Corona | California | United States | -117.56644 | 33.87529
Encinitas | California | United States | -117.29198 | 33.03699
Highland | California | United States | -117.20865 | 34.12834
Los Angeles | California | United States | -118.24368 | 34.05223
Orange | California | United States | -117.85311 | 33.78779
Sacramento | California | United States | -121.4944 | 38.58157
Denver | Colorado | United States | -104.9847 | 39.73915
Lakeland | Florida | United States | -81.9498 | 28.03947
Merritt Island | Florida | United States | -80.69 | 28.359
Orlando | Florida | United States | -81.37924 | 28.53834
Orlando | Florida | United States | -81.37924 | 28.53834
Atlanta | Georgia | United States | -84.38798 | 33.749
Marietta | Georgia | United States | -84.54993 | 33.9526
Savannah | Georgia | United States | -81.09983 | 32.08354
Chicago | Illinois | United States | -87.65005 | 41.85003
Skokie | Illinois | United States | -87.73339 | 42.03336
Skokie | Illinois | United States | -87.73339 | 42.03336
Fort Wayne | Indiana | United States | -85.12886 | 41.1306
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Kokomo | Indiana | United States | -86.1336 | 40.48643
Sioux City | Iowa | United States | -96.40031 | 42.49999
Hutchinson | Kansas | United States | -97.92977 | 38.06084
Wichita | Kansas | United States | -97.33754 | 37.69224
Louisville | Kentucky | United States | -85.75941 | 38.25424
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
Metairie | Louisiana | United States | -90.15285 | 29.98409
Boston | Massachusetts | United States | -71.05977 | 42.35843
Pittsfield | Massachusetts | United States | -73.24538 | 42.45008
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
Detroit | Michigan | United States | -83.04575 | 42.33143
Hattiesburg | Mississippi | United States | -89.29034 | 31.32712
Jefferson City | Missouri | United States | -92.17352 | 38.5767
Kansas City | Missouri | United States | -94.57857 | 39.09973
Kansas City | Missouri | United States | -94.57857 | 39.09973
St Louis | Missouri | United States | -90.19789 | 38.62727
Lincoln | Nebraska | United States | -96.66696 | 40.8
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Hackensack | New Jersey | United States | -74.04347 | 40.88593
Morristown | New Jersey | United States | -74.48154 | 40.79677
New York | New York | United States | -74.00597 | 40.71427
Rochester | New York | United States | -77.61556 | 43.15478
Staten Island | New York | United States | -74.13986 | 40.56233
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Fargo | North Dakota | United States | -96.7898 | 46.87719
Columbus | Ohio | United States | -82.99879 | 39.96118
Columbus | Ohio | United States | -82.99879 | 39.96118
Dayton | Ohio | United States | -84.19161 | 39.75895
Dover | Ohio | United States | -81.47401 | 40.52062
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Portland | Oregon | United States | -122.67621 | 45.52345
Allentown | Pennsylvania | United States | -75.49018 | 40.60843
Bethlehem | Pennsylvania | United States | -75.37046 | 40.62593
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pottsville | Pennsylvania | United States | -76.1955 | 40.68565
Sayre | Pennsylvania | United States | -76.5155 | 41.97896
Charleston | South Carolina | United States | -79.93275 | 32.77632
Greenville | South Carolina | United States | -82.39401 | 34.85262
Knoxville | Tennessee | United States | -83.92074 | 35.96064
Nashville | Tennessee | United States | -86.78444 | 36.16589
Trophy Club | Texas | United States | -97.18362 | 32.9979
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Abingdon | Virginia | United States | -81.97735 | 36.70983
Fairfax | Virginia | United States | -77.30637 | 38.84622
Richlands | Virginia | United States | -81.79373 | 37.09317
Richmond | Virginia | United States | -77.46026 | 37.55376
Richmond | Virginia | United States | -77.46026 | 37.55376
Morgantown | West Virginia | United States | -79.9559 | 39.62953
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
El Palomar - Morón | Buenos Aires | Argentina | N/A | N/A
La Plata | Buenos Aires | Argentina | -57.95442 | -34.92126
Mar del Plata | Buenos Aires | Argentina | -57.5562 | -38.00042
Buenos Aires | Ciudad Auton. de Buenos Aires | Argentina | -58.37723 | -34.61315
Rosario | Santa Fe Province | Argentina | -60.63932 | -32.94682
Capital Federal-Buenos Aires | N/A | Argentina | N/A | N/A
Santa Fé | N/A | Argentina | N/A | N/A
Port Macquarie | New South Wales | Australia | 152.90894 | -31.43084
Wollongong | New South Wales | Australia | 150.89345 | -34.424
Brisbane | Queensland | Australia | 153.02809 | -27.46794
Adelaide | South Australia | Australia | 138.59863 | -34.92866
Frankston | Victoria | Australia | 145.12291 | -38.14458
Melbourne | Victoria | Australia | 144.96332 | -37.814
Perth | Western Australia | Australia | 115.8614 | -31.95224
Bruxelles - Brussel | N/A | Belgium | N/A | N/A
Charleroi | N/A | Belgium | 4.44448 | 50.41136
La Louvière | N/A | Belgium | 4.18785 | 50.48657
Liège | N/A | Belgium | 5.56749 | 50.63373
Fortaleza | Ceará | Brazil | -38.54306 | -3.71722
Fortaleza | Ceará | Brazil | -38.54306 | -3.71722
Salvador | Estado de Bahia | Brazil | -38.49096 | -12.97563
Brasília | Federal District | Brazil | -47.92972 | -15.77972
Goiânia | Goiás | Brazil | -49.25389 | -16.67861
Nova Lima | Minas Gerais | Brazil | -43.84667 | -19.98556
Curitiba | Paraná | Brazil | -49.27306 | -25.42778
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
Joinville | Santa Catarina | Brazil | -48.84556 | -26.30444
Barretos | São Paulo | Brazil | -48.56778 | -20.55722
Jaú | São Paulo | Brazil | -48.55778 | -22.29639
Ribeirão Preto | São Paulo | Brazil | -47.81028 | -21.1775
Santo André | São Paulo | Brazil | -46.53833 | -23.66389
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
Sorocaba | São Paulo | Brazil | -47.45806 | -23.50167
Belo Horizonte | N/A | Brazil | -43.93778 | -19.92083
North Vancouver | British Columbia | Canada | -123.06934 | 49.31636
Barrie | Ontario | Canada | -79.66634 | 44.40011
Brampton | Ontario | Canada | -79.76633 | 43.68341
Montreal | Quebec | Canada | -73.58781 | 45.50884
Regina | Saskatchewan | Canada | -104.6178 | 50.45008
Santiago | Santiago Metropolitan | Chile | -70.64827 | -33.45694
Santiago | N/A | Chile | -70.64827 | -33.45694
Santiago | N/A | Chile | -70.64827 | -33.45694
Santiago | N/A | Chile | -70.64827 | -33.45694
Bobigny | N/A | France | 2.45012 | 48.90982
Caen | N/A | France | -0.35912 | 49.18585
Clamart | N/A | France | 2.26692 | 48.80299
Metz | N/A | France | 6.17269 | 49.11911
Nancy | N/A | France | 6.18496 | 48.68439
Nice | N/A | France | 7.26608 | 43.70313
Strasbourg | N/A | France | 7.74553 | 48.58392
Heidelberg | Baden-Wurttemberg | Germany | 8.69079 | 49.40768
Mannheim | Baden-Wurttemberg | Germany | 8.46694 | 49.4891
Gauting | Bavaria | Germany | 11.37703 | 48.06919
München | Bavaria | Germany | 13.46314 | 48.69668
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hofheim | Hesse | Germany | 8.41385 | 49.65749
Göttingen | Lower Saxony | Germany | 9.93228 | 51.53443
Hanover | Lower Saxony | Germany | 9.73322 | 52.37052
Oldenburg | Lower Saxony | Germany | 8.21467 | 53.14118
Essen | North Rhine-Westphalia | Germany | 7.01228 | 51.45657
Essen | North Rhine-Westphalia | Germany | 7.01228 | 51.45657
Hemer | North Rhine-Westphalia | Germany | 7.77019 | 51.38707
Leverkusen | North Rhine-Westphalia | Germany | 6.98432 | 51.0303
Mainz | Rhineland-Palatinate | Germany | 8.2791 | 49.98419
Großhansdorf | Schleswig-Holstein | Germany | 10.28333 | 53.66667
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Hong Kong | N/A | Hong Kong | 114.17469 | 22.27832
Budapest | N/A | Hungary | 19.04045 | 47.49835
Deszk | N/A | Hungary | 20.24322 | 46.21802
Gyula | N/A | Hungary | 21.28333 | 46.65
Mátraháza | N/A | Hungary | 19.97981 | 47.87124
Törökbálint | N/A | Hungary | 18.91356 | 47.42931
Orbassano | Torino | Italy | 7.53813 | 45.00547
Bergamo | N/A | Italy | 9.66721 | 45.69601
Genova | N/A | Italy | 11.87211 | 45.21604
Milan | N/A | Italy | 12.59836 | 42.78235
Parma | N/A | Italy | 10.32618 | 44.79935
Pavia | N/A | Italy | 9.15917 | 45.19205
Perugia | N/A | Italy | 12.38878 | 43.1122
Roma | N/A | Italy | 11.10642 | 44.99364
Torino | N/A | Italy | 11.99138 | 44.88856
Eindhoven | North Brabant | Netherlands | 5.47778 | 51.44083
Zwolle | N/A | Netherlands | 6.09444 | 52.5125
Gdansk | N/A | Poland | 18.64912 | 54.35227
Krakow | N/A | Poland | 19.93658 | 50.06143
Olsztyn | N/A | Poland | 20.49416 | 53.77995
Otwock | N/A | Poland | 21.26129 | 52.10577
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
San Juan | N/A | Puerto Rico | -66.10572 | 18.46633
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Alicante | Alicante | Spain | -0.48149 | 38.34517
Elche | Alicante | Spain | -0.70107 | 38.26218
Zaragoza | Aragon | Spain | -0.87734 | 41.65606
Barcelona | Barcelona | Spain | 2.15899 | 41.38879
Madrid | Madrid | Spain | -3.70256 | 40.4165
Madrid | Madrid | Spain | -3.70256 | 40.4165
Majadahonda | Madrid | Spain | -3.87182 | 40.47353
Pontevedra | Pontevedra | Spain | -8.64435 | 42.431
Zamora | Zamora | Spain | -5.74456 | 41.50633
Gävle | N/A | Sweden | 17.14174 | 60.67452
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Uppsala | N/A | Sweden | 17.63889 | 59.85882
Taichung | N/A | Taiwan | 120.6839 | 24.1469
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taoyuan District | N/A | Taiwan | 121.3187 | 24.9896
Plymouth | Devon | United Kingdom | -4.14305 | 50.37153
Bornemouth | Dorset | United Kingdom | N/A | N/A
Leicester | Leicestershire | United Kingdom | -1.13169 | 52.6386
London | London | United Kingdom | -0.12574 | 51.50853
Manchester | Manchester | United Kingdom | -2.23743 | 53.48095
| 0
|
NCT00300885
|
[
3
] | 14
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The aim of this study is to evaluate the efficacy, safety and tolerability of aripiprazole monotherapy in the treatment of children and adolescents suffering from Autism Spectrum Disorder (ASD) over a 12-week period. We hypothesize that aripiprazole may be helpful in reducing ASD-associated symptoms of anxiety and aggression, resulting in significant improvements in global outcome.
|
Study Design: Fifteen patients with DSM-IV diagnoses of Autism, Asperger's Disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS) will be enrolled in this 12-week open-label study. Parents of potential subjects will do a preliminary phone screen, followed by a clinical evaluation by a psychiatrist for possible inclusion in the study. Informed written consent and assent will be obtained from the parents and subjects respectively once deemed competent and before the initiation of any study procedures.
Clinical Evaluation will use the Autism Diagnostic Interview (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) to establish a formal diagnosis.
Study Procedures Baseline Assessments: Many baseline measures for physical health will be done at the screening visit and during the first weekly visit. These will include a clinical interview, physical and neurological examination will be done during the screening period and height, weight and vital signs, and a calculation of his/her Body Mass Index (BMI) will be done during the screening period and during the first weekly visit. Laboratory measures at baseline and study completion will include a complete metabolic panel (with liver transaminases) and complete blood count with differential. Further measures will include a fasting lipid profile, hemoglobin A1C, prolactin level and insulin levels, and fasting blood sugar level (FBS). Serum albumin will be measured not only as a measure of nutritional state, but also in accordance with the fact that aripiprazole is 99% protein-bound. An electrocardiogram (ECG) will be performed at the beginning and end of the study to monitor for possible cardiac effects. These measures are aimed at monitoring side effects reported in the use of other medications in this class. Urine pregnancy tests will be performed for each female subject at the beginning and end of the study.
Outcome measures will include the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Brief Psychiatric Rating Scale for children (BPRS-C), Clinical Global Impression - Severity (CGI-S), Vineland Adaptive Behavior Scale (VABS) and the Atypical Children's Development Scale (ACDS).
Baseline parameters for extrapyramidal side effects will be established using the Abnormal Involuntary Movement Scale (AIMS), the Simpson Angus Extrapyramidal Side Effect Scale (SAEPS) and the Barnes Akathisia Rating Scale. Baseline values for general side effects will be compiled using the Monitoring of Side Effects System (MOSES).
Weekly visits: At all visits, patients will undergo a clinical interview, vital signs, and weight measures. Custodial guardian(s) will provide collateral information. The weekly "short" visits will occur at weeks 2, 4, 6, 8, 10 and 12. They will be about 45 minutes in duration.
Ongoing outcome measures will be performed at visits 3, 5, 7, 9 and 11. The visits will be about 1-1.5 hours in duration. The measures done will include those at the short visits, as well as the Y-BOCS, BPRS, ABC and CGI-S. Side effects will be monitored using the AIMS, SAEPS, Barnes Akathisia Scale and MOSES at these visits.
Termination Visit: The last visit (Visit 13 or earlier if patient drops out of the study) will include the repetition of all measures at visit 1 (except the ADI-R) and will last about 2 hours. All baseline laboratory measures will be repeated at this time.
Follow-Up Patient Care: After completion of the clinical trial, the patients will be followed at the Cambridge Health Alliance (CHA) Center for Child and Adolescent Development until they can be referred back to their original psychiatric providers or to appropriate treatment providers in the community.
Medication dosing: Aripiprazole will be started at 2.5mg or 5mg depending on clinical impression and severity of especially aggression and agitation. At the weekly visits, the dose will be adjusted in not more than 5mg increments according to clinical impression. The lowest effective dose will be used, up to a maximum dose of 20mg.
Patients already taking psychotropic medications will be tapered off their medications during the first 1-2 weeks of the study. The dose will be reduced to 67% of the initial dose for 3 days and then to 33% of the initial dose for 3 days and then the medication(s) will be discontinued. The subjects will remain off of on enrollment medications for 5 half lives and then aripiprazole will be initiated. Anticonvulsant medications taken for seizure control may be continued throughout the trial as long as the subject has been on a stable dose for 30 days prior to the study and has been seizure free for 6 months. These medication doses will be held stable throughout the trial.
Adverse Events: Any serious adverse event leading to hospitalization will lead to study discontinuation. Any event requiring concomitant medication(s) will also lead to discontinuation. Adverse events will be reported to the Institutional Review Board (IRB) if there is an event requiring medical attention, or scores 3 or higher on the MOSES scale. Also, failure to comply with the study instructions will result in termination from the protocol.
|
Autism Asperger's Disorder Pervasive Developmental Disorder
|
behavioral problems aggression autism aripiprazole
| null | 1
|
arm 1: aripiprazole monotherapy, begun at 2.5 mg or 5.0 mg based on clinical impression and severity of aggression and agitation. Dose to be adjusted in not more than 5 mg increments, weekly. The lowest effective dose will be used up to a maximum daily dose of 20 mg.
|
[
0
] | 1
|
[
0
] |
intervention 1: open-label, flexible-dosing
|
intervention 1: Aripiprazole
| 1
|
Medford | Massachusetts | United States | -71.10616 | 42.41843
| 0
|
NCT00308074
|
[
3
] | 75
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 1FEMALE
| false
|
The purpose of this study is to determine if SKI-606 (Bosutinib) is effective in the treatment of advanced or metastatic breast cancer. Patients must have current Stage IIIB, IIIC or IV breast cancer and have progressed after 1 to 3 prior chemotherapy regimens.
| null |
Breast Neoplasms Neoplasm Metastasis
|
Advanced Breast Cancer
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: SKI-606 (Bosutinib) 400mg once daily, for as long as tolerated or until disease progression.
|
intervention 1: SKI-606 (Bosutinib)
| 15
|
Duarte | California | United States | -117.97729 | 34.13945
Santa Monica | California | United States | -118.49138 | 34.01949
Tampa | Florida | United States | -82.45843 | 27.94752
Cleveland | Ohio | United States | -81.69541 | 41.4995
Darlinghurst | New South Wales | Australia | 151.21925 | -33.87939
Dijon | N/A | France | 5.01667 | 47.31667
Saint-Herblain | N/A | France | -1.651 | 47.21154
Pokfulam | N/A | Hong Kong | N/A | N/A
Floriana | N/A | Malta | 14.50833 | 35.89583
Lodz | N/A | Poland | 19.47395 | 51.77058
Wroclaw | N/A | Poland | 17.03333 | 51.1
Moscow | N/A | Russia | 37.61556 | 55.75222
Sumy | Ukraine | Ukraine | 34.79906 | 50.91741
Dnipropetrovsk | N/A | Ukraine | 35.04066 | 48.46664
Uzhhorod | N/A | Ukraine | 22.2947 | 48.6242
| 0
|
NCT00319254
|
[
2
] | 42
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 1FEMALE
| false
|
Tumor response information was obtained for all participants who received at least 2 cycles of study drug, underwent requisite baseline and on-treatment disease assessments and had at least one post-treatment assessment. Tumor response assessment in evaluable participants was done according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
| null |
Metastatic Breast Cancer
| null | 3
|
arm 1: Participants received 25 mg/m\^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m\^2 epirubicin every 21 days. arm 2: Participants received 30 mg/m\^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m\^2 epirubicin every 21 days. arm 3: Participants received 35 mg/m\^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m\^2 epirubicin every 21 days.
|
[
0,
0,
0
] | 2
|
[
0,
0
] |
intervention 1: Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study. intervention 2: Infusion, intravenous (IV): 75 mg/m\^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².
|
intervention 1: Ixabepilone intervention 2: Epirubicin
| 2
|
Toulouse | N/A | France | 1.44367 | 43.60426
Milan | N/A | Italy | 12.59836 | 42.78235
| 0
|
NCT00322374
|
|
[
4
] | 1,428
|
RANDOMIZED
|
PARALLEL
| 4SUPPORTIVE_CARE
| 2DOUBLE
| false
| 0ALL
| false
|
This randomized phase III trial is studying APF530 and dexamethasone to see how well they work compared with palonosetron and dexamethasone in preventing nausea and vomiting in patients receiving chemotherapy for cancer.
|
OBJECTIVES:
Primary
* Compare the overall activity and effects of APF530 versus palonosetron hydrochloride in combination with dexamethasone for prophylaxis of acute- or delayed-onset, chemotherapy-induced nausea and vomiting in patients undergoing moderately or highly emetogenic chemotherapy for cancer.
Secondary
* Evaluate the safety, tolerability, and efficacy of APF530, in terms of prevention of acute- and delayed-onset nausea and vomiting, in these patients.
* Gather the pharmacokinetics of APF530 in a subset of patients during chemotherapy course 1.
* Gather ECG data (using 24-hour Holter monitoring) in a subset of patients during chemotherapy course 1.
OUTLINE: This is a randomized, placebo-controlled, double-blind, parallel-group, multicenter study. Patients are stratified according to emetogenicity of scheduled chemotherapy (moderate-risk \[level 3 or 4\] vs high-risk \[level 5\]). Patients are randomized to 1 of 3 treatment arms (I, II, and III). Patients who are randomized to receive palonosetron hydrochloride during chemotherapy course 1 (arm I) are then re-randomized to 1 of 2 treatment arms (II and III) after chemotherapy course 1 to receive treatment during chemotherapy courses 2-4.
Patients receive palonosetron hydrochloride or APF530 and/or placebo 30-60 minutes before the start of chemotherapy. Patients receive dexamethasone 30-90 minutes before the start of chemotherapy.
* Arm I: Patients receive palonosetron hydrochloride IV, placebo subcutaneously (SC), and dexamethasone IV on day 1 of chemotherapy course 1. Patients in the high-risk (level 5) stratum also receive oral dexamethasone on days 2-4 of all treatment courses.
* Arm II: Patients receive APF530 SC, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
* Arm III: Patients receive APF530 SC at a higher dose, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC (at the same higher dose) and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
A subset of patients undergo blood collection periodically during study for analysis of plasma APF530 concentration.
Quality of life is assessed on day 5 after completion of chemotherapy course 1.
After completion of study treatment, patients are followed at approximately 30 days.
|
Nausea and Vomiting Unspecified Adult Solid Tumor, Protocol Specific
|
nausea and vomiting unspecified adult solid tumor, protocol specific
| null | 3
|
arm 1: Patients receive palonosetron hydrochloride IV, placebo subcutaneously (SC), and dexamethasone IV on day 1 of chemotherapy course 1. Patients in the high-risk (level 5) stratum also receive oral dexamethasone on days 2-4 of all treatment courses. arm 2: Patients receive APF530 SC, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I. arm 3: Patients receive APF530 SC at a higher dose, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC (at the same higher dose) and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
|
[
1,
0,
0
] | 4
|
[
0,
0,
0,
10
] |
intervention 1: Given subcutanously intervention 2: Given IV and orally intervention 3: Given IV intervention 4: Given subcutanously or IV
|
intervention 1: APF530 intervention 2: dexamethasone intervention 3: Palonosetron Hydrochloride intervention 4: placebo
| 52
|
Anniston | Alabama | United States | -85.83163 | 33.65983
Glendale | Arizona | United States | -112.18599 | 33.53865
Tucson | Arizona | United States | -110.92648 | 32.22174
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Anaheim | California | United States | -117.9145 | 33.83529
Campbell | California | United States | -121.94996 | 37.28717
Corona | California | United States | -117.56644 | 33.87529
Fountain Valley | California | United States | -117.95367 | 33.70918
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Orange | California | United States | -117.85311 | 33.78779
Norwich | Connecticut | United States | -72.07591 | 41.52426
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
New Port Richey | Florida | United States | -82.71927 | 28.24418
North Miami Beach | Florida | United States | -80.16255 | 25.93315
Columbus | Georgia | United States | -84.98771 | 32.46098
Skokie | Illinois | United States | -87.73339 | 42.03336
Indianapolis | Indiana | United States | -86.15804 | 39.76838
New Albany | Indiana | United States | -85.82413 | 38.28562
Vincennes | Indiana | United States | -87.52863 | 38.67727
Vincennes | Indiana | United States | -87.52863 | 38.67727
Hazard | Kentucky | United States | -83.19323 | 37.24954
Louisville | Kentucky | United States | -85.75941 | 38.25424
Lewiston | Maine | United States | -70.21478 | 44.10035
Baltimore | Maryland | United States | -76.61219 | 39.29038
Bethesda | Maryland | United States | -77.10026 | 38.98067
Hagerstown | Maryland | United States | -77.71999 | 39.64176
Petoskey | Michigan | United States | -84.95533 | 45.37334
Pascagoula | Mississippi | United States | -88.55613 | 30.36576
Kansas City | Missouri | United States | -94.57857 | 39.09973
Phillipsburg | New Jersey | United States | -75.19018 | 40.69371
Buffalo | New York | United States | -78.87837 | 42.88645
Elmira | New York | United States | -76.80773 | 42.0898
Poughkeepsie | New York | United States | -73.92097 | 41.70037
Hendersonville | North Carolina | United States | -82.46095 | 35.31873
Rocky Mount | North Carolina | United States | -77.79053 | 35.93821
Rocky Mount | North Carolina | United States | -77.79053 | 35.93821
Akron | Ohio | United States | -81.51901 | 41.08144
Canton | Ohio | United States | -81.37845 | 40.79895
Dover | Ohio | United States | -81.47401 | 40.52062
Mansfield | Ohio | United States | -82.51545 | 40.75839
Middletown | Ohio | United States | -84.39828 | 39.51506
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Pottsville | Pennsylvania | United States | -76.1955 | 40.68565
Charleston | South Carolina | United States | -79.93275 | 32.77632
Beaumont | Texas | United States | -94.10185 | 30.08605
San Antonio | Texas | United States | -98.49363 | 29.42412
Abingdon | Virginia | United States | -81.97735 | 36.70983
Richlands | Virginia | United States | -81.79373 | 37.09317
Lacey | Washington | United States | -122.82319 | 47.03426
Tacoma | Washington | United States | -122.44429 | 47.25288
Morgantown | West Virginia | United States | -79.9559 | 39.62953
| 0
|
NCT00343460
|
[
4
] | 21
|
RANDOMIZED
|
PARALLEL
| 4SUPPORTIVE_CARE
| 3TRIPLE
| false
| 0ALL
| true
|
RATIONALE: Growth factors, such as palifermin, may lessen the severity of mucositis, or mouth sores, in patients receiving radiation therapy and chemotherapy for head and neck cancer. It is not yet known whether palifermin is more effective than a placebo in lessening mucositis in patients receiving radiation therapy and chemotherapy for head and neck cancer.
PURPOSE: This randomized phase III trial is studying palifermin to see how well it works compared to a placebo in lessening oral mucositis in patients undergoing radiation therapy and chemotherapy for locally advanced head and neck cancer.
|
OBJECTIVES:
Primary
* Compare the efficacy of palifermin vs placebo, in terms of burden of acute mucositis (defined to be 105 days \[15 weeks\] or less from the start of treatment), in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing concurrent radiotherapy and chemotherapy.
Secondary
* Compare incidence and time to onset of Grades 3 or 4 oral mucositis in patients treated with these regimens.
* Compare overall and progression-free survival and time to second primary in patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (III vs IVA or IVB), tumor site (oral cavity or oropharynx vs hypopharynx or larynx), and radiotherapy technique used on study (intensity-modulated radiotherapy \[IMRT\] vs 3-dimensional conformal radiotherapy \[3D-CRT\]). Patients are randomized to 1 of 2 treatment arms.
Mucositis, pain, and symptom burden are assessed at baseline, during radiotherapy, and post radiotherapy. Xerostomia is assessed at baseline, during radiotherapy, and several times after completion of study therapy.
After completion of study therapy, patients are followed periodically for 10 years.
PROJECTED ACCRUAL: A total of 298 patients will be accrued for this study.
|
Head and Neck Cancer Mucositis Pain Radiation Toxicity
|
mucositis pain radiation toxicity stage III squamous cell carcinoma of the hypopharynx stage IV squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx stage III squamous cell carcinoma of the lip and oral cavity stage IV squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx
| null | 2
|
arm 1: Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients. arm 2: Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.
|
[
0,
2
] | 5
|
[
2,
0,
10,
3,
4
] |
intervention 1: Four doses of palifermin, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19. intervention 2: Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course. intervention 3: Four doses of placebo, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19. intervention 4: A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy. A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck. All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline. intervention 5: A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa. Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.
|
intervention 1: palifermin intervention 2: cisplatin intervention 3: placebo intervention 4: neck dissection intervention 5: radiation therapy
| 48
|
Scottsdale | Arizona | United States | -111.89903 | 33.50921
Auburn | California | United States | -121.07689 | 38.89657
Burbank | California | United States | -118.30897 | 34.18084
Cameron Park | California | United States | -120.98716 | 38.66879
Carmichael | California | United States | -121.32828 | 38.61713
Chico | California | United States | -121.83748 | 39.72849
Duarte | California | United States | -117.97729 | 34.13945
Los Angeles | California | United States | -118.24368 | 34.05223
Roseville | California | United States | -121.28801 | 38.75212
Sacramento | California | United States | -121.4944 | 38.58157
Sacramento | California | United States | -121.4944 | 38.58157
Torrance | California | United States | -118.34063 | 33.83585
Vacaville | California | United States | -121.98774 | 38.35658
Newark | Delaware | United States | -75.74966 | 39.68372
Anderson | Indiana | United States | -85.68025 | 40.10532
Baltimore | Maryland | United States | -76.61219 | 39.29038
Detroit | Michigan | United States | -83.04575 | 42.33143
Iron Mountain | Michigan | United States | -88.06596 | 45.82023
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Royal Oak | Michigan | United States | -83.14465 | 42.48948
Rochester | Minnesota | United States | -92.4699 | 44.02163
Saint Cloud | Minnesota | United States | -94.16249 | 45.5608
Pascagoula | Mississippi | United States | -88.55613 | 30.36576
Great Falls | Montana | United States | -111.30081 | 47.50024
Camden | New Jersey | United States | -75.11962 | 39.92595
Vineland | New Jersey | United States | -75.02573 | 39.48623
Voorhees Township | New Jersey | United States | -74.49062 | 40.4795
Durham | North Carolina | United States | -78.89862 | 35.99403
Greenville | North Carolina | United States | -77.36635 | 35.61266
Akron | Ohio | United States | -81.51901 | 41.08144
Akron | Ohio | United States | -81.51901 | 41.08144
Salem | Ohio | United States | -80.85675 | 40.90089
Wooster | Ohio | United States | -81.93646 | 40.80517
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Hermitage | Pennsylvania | United States | -80.44868 | 41.23339
Monroeville | Pennsylvania | United States | -79.7881 | 40.42118
Natrona Heights | Pennsylvania | United States | -79.72977 | 40.6234
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Somerset | Pennsylvania | United States | -79.07808 | 40.00841
State College | Pennsylvania | United States | -77.86 | 40.79339
Johnson City | Tennessee | United States | -82.35347 | 36.31344
Houston | Texas | United States | -95.36327 | 29.76328
Wheeling | West Virginia | United States | -80.72091 | 40.06396
Green Bay | Wisconsin | United States | -88.01983 | 44.51916
Marinette | Wisconsin | United States | -87.63066 | 45.09998
Edmonton | Alberta | Canada | -113.46871 | 53.55014
| 0
|
NCT00360971
|
[
4
] | 51
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 1SINGLE
| false
| 0ALL
| false
|
Treatment of anemia associated with chronic kidney disease (CKD) during 36 weeks with safety follow up phase of 52 weeks
|
This is a multicentre, randomised, single-blind, placebo-controlled, two-arm parallel group study assessing the effect of anaemia correction and Hb maintenance with darbepoetin alfa in elderly CKD patients for 36 weeks.
|
Anemia Chronic Kidney Disease
|
Quality of Life Chronic Kidney Disease Anemia
| null | 2
|
arm 1: Single-blind darbepoetin alfa administered by subcutaneous injection (SC) every other week until hemoglobin (Hgb) was stable (2 consecutive Hgb values between 120 and 135 g/L), then every month for up to 9 months. arm 2: Single-blind placebo administered by subcutaneous injection (SC) every other week until week 16, then every month for up to 9 months.
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: Starting dose was calculated at 0.75 micrograms per kilogram (μg/kg) body weight at randomization, rounded to nearest prefilled syringe dose unit. Dose was titrated incrementally. Monthly dose was initially double the every 2 week dose at time of conversion. intervention 2: Prefilled syringe placebo, to match active arm
|
intervention 1: Darbepoetin alfa intervention 2: Placebo
| 0
| null | 0
|
NCT00364845
|
[
4
] | 25
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
This is an open label, randomized, comparative, multi-center study. Subjects will be screened within 2 weeks prior to study entry to establish eligibility. Subjects who meet all the selection criteria will be randomly assigned 1:1 to (1) once-a-week, subcutaneous Pegylated interferon alfa-2b (PegIntron) (1.5 mcg/kg body weight) or (2) oral adefovir 10 mg daily. The treatment phase will be 24 weeks for PegIntron and 48 weeks for adefovir. All subjects completing the assigned treatment phase will be followed up for an additional 48 weeks for PegIntron and 24 weeks for adefovir as observation phase. The primary objective is to establish the efficacy profile of PegIntron. Secondary objectives are to compare the efficacy profile of PegIntron with that of adefovir, compare efficacy of PegIntron in lamivudine-naïve and lamivudine-experienced subjects, and to establish the safety profile of PegIntron in treating patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
| null |
Hepatitis B, Chronic (CHB)
|
Hepatitis B virus Pegylated interferon alfa-2b (PegIntron)
| null | 2
|
arm 1: PegIntron, 1.5 micrograms/kg weekly, for up to 24 weeks followed by a 48-week observation phase arm 2: Adefovir, 10 mg daily, for up to 48 weeks followed by a 24-week observation phase
|
[
0,
1
] | 2
|
[
2,
0
] |
intervention 1: Powder for injection in vials ( 100, and 120 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 weeks intervention 2: 10 mg adefovir dipivoxil (equivalent to 5.4.5 mg adefovir) tablets, oral, dose of 1 tablet per day for up to 48 weeks
|
intervention 1: Pegylated interferon alfa-2b (PegIntron) intervention 2: Adefovir dipivoxil (adefovir)
| 0
| null | 0
|
NCT00371761
|
[
3
] | 14
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
This phase II trial is studying how well sunitinib works in treating patients with idiopathic myelofibrosis. Sunitinib may stop the growth of abnormal cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the abnormal cells.
|
PRIMARY OBJECTIVE:
I. Assess the response rate and the duration of response in patients with idiopathic myelofibrosis treated with sunitinib malate.
SECONDARY OBJECTIVE:
I. Assess the safety of sunitinib malate in these patients.
OUTLINE: This is an open-label, multicenter study.
Patients receive oral sunitinib malate once daily for 6 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 4 weeks.
|
Accelerated Phase Chronic Myelogenous Leukemia Acute Undifferentiated Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Blastic Phase Chronic Myelogenous Leukemia Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia Mast Cell Leukemia Meningeal Chronic Myelogenous Leukemia Primary Myelofibrosis Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia T-cell Large Granular Lymphocyte Leukemia Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Hairy Cell Leukemia
| null | 1
|
arm 1: Patients receive oral sunitinib malate once daily for 6 weeks.
|
[
0
] | 1
|
[
0
] |
intervention 1: Given PO
|
intervention 1: sunitinib malate
| 1
|
Houston | Texas | United States | -95.36327 | 29.76328
| 0
|
NCT00387426
|
|
[
4
] | 77
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
The purpose of this study is to evaluate how children and adolescents with Attention Deficit/ Hyperactivity Disorder (ADHD) respond to treatment with three differing doses of stimulant medications used to treat ADHD, Adderall XR® and Focalin XR®. Another purpose of the study is to evaluate if there are differences in sleep and other side effects, such as changes in mood or loss of appetite, which can occur with stimulant medications. A third purpose is to determine if there are differences in the characteristics of individuals who respond better to either of the medications.
This research is being done because the investigators do not know if one of these two commonly used treatments is better tolerated than the other. Children and adolescents with ADHD often have a hard time sitting still, playing quietly, finishing things they start, paying attention, waiting their turn, and not distracting others. These medications improve these symptoms, but sometimes affect sleep, appetite, or mood.
It is hypothesized that at effective and frequently prescribed doses, Adderall will be associated with insomnia, more stimulant side effects, and decreased tolerability during an acute trial relative to Focalin.
|
ADHD is often treated with stimulant medications, which have demonstrated short-term efficacy in numerous trials. However, treatment is often discontinued prematurely. Although ADHD often persists through adolescence, approximately half of all children who are treated with a stimulant medication discontinue treatment within one year (Charach, Ickowicz et al. 2004). Presumably, tolerability and treatment compliance are highly related to the side effect profile of stimulant medications (Schachar, Jadad et al. 2002). Sleep problems, particularly insomnia, are frequently associated with ADHD and are often exacerbated by stimulant medications, particularly at higher doses. Other frequent stimulant side effects are decreased appetite and mood lability (dysphoria/euphoria). Little is known about the relative effects of different stimulant formulations and dosages (i.e amphetamine, methylphenidate, dexmethylphenidate) on sleep and tolerability. There is some preliminary data with short acting stimulants suggesting a higher prevalence of sleep and appetite problems with amphetamine relative to mph (Pelham, Aronoff et al. 1999). Several studies indicate that sleep and other stimulant side effects are dose related (Stein, Sarampote et al. 2003), although this has not been found in all studies. Moreover, it is unclear if there are differences between long-acting amphetamine and methylphenidate based stimulants in their side effect profile and tolerability. Thus, we will directly compare these two long acting stimulant medications on their side effect profile and tolerability, including measures of sleep, mood, and evening behavior (e.g., family conflicts). The recently developed extended release formulation of dexmethylphenidate will be compared to one of the most common treatments for ADHD, extended release formulation of mixed amphetamine salts. The subject population will be older children and adolescents (10-17) with ADHD who are most likely to be treated with moderate to higher dose levels of stimulant medications and can complete all self-report measures.
|
Attention Deficit Hyperactivity Disorder
|
Attention Deficit Hyperactivity Disorder sleep side effects stimulants
| null | 2
|
arm 1: Subjects are given the Focalin XR first (dexmethylphenidate) for four weeks with a randomized placebo week followed by Adderall XR (mixed amphetamine salts) for four weeks with a randomized placebo week. arm 2: Subjects are given the Adderall XR (mixed amphetamine salts) for four weeks with a randomized placebo week followed by Focalin XR first (dexmethylphenidate) for four weeks with a randomized placebo week.
|
[
0,
0
] | 3
|
[
0,
0,
0
] |
intervention 1: 10, 20, 25-30 mg. intervention 2: 10, 20, 25-30 intervention 3: randomized placebo week during each 4 week period
|
intervention 1: Dexmethylphenidate intervention 2: Mixed Amphetamine Salts, ER intervention 3: placebo
| 2
|
Chicago | Illinois | United States | -87.65005 | 41.85003
Northbrook | Illinois | United States | -87.82895 | 42.12753
| 0
|
NCT00393042
|
[
3
] | 138
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
This is a 24-month study to evaluate multiple doses of AGN211745 (previously known as Sirna-027) in treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration
| null |
Choroid Neovascularization Age-Related Macular Degeneration
| null | 4
|
arm 1: AGN 211745 Solution 1000 ug arm 2: AGN 211745 Solution 300 ug arm 3: AGN 211745 Solution 100 ug arm 4: Ranibizumab 500 ug
|
[
0,
0,
0,
1
] | 4
|
[
0,
0,
0,
0
] |
intervention 1: AGN 211745 Solution 1000µg injection at Day 1, Month 1, Month 2 intervention 2: AGN 211745 Solution 300µg injections, Day 1, Month 1, Month 2 intervention 3: AGN 211745 Solution 100µg injections, Day 1, Month 1, Month 2 intervention 4: Ranibizumab 500µg injections at Day 1, Month 1, Month 2
|
intervention 1: AGN 211745 intervention 2: AGN 211745 intervention 3: AGN 211745 intervention 4: Ranibizumab 500µg
| 3
|
Houston | Texas | United States | -95.36327 | 29.76328
Sydney | New South Wales | Australia | 151.20732 | -33.86785
Makati | N/A | Philippines | 121.1226 | 16.412
| 0
|
NCT00395057
|
|
[
4
] | 159
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
To evaluate the combination of telbivudine 600 mg orally (PO) once daily and peginterferon alpha-2a 180 ug subcutaneous (sq) injection weekly for antiviral efficacy in comparison to peginterferon alpha-2a monotherapy.
| null |
Hepatitis B
|
hepatitis B hepatitis B Virus (HBV) chronic hepatitis B telbivudine peginterferon
| null | 3
|
arm 1: Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peginterferon alpha-2a (PEG-INF)180 μg subcutaneous injection once a week for 52 weeks. arm 2: Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks. arm 3: Peginterferon alpha-2a (PEG- INF) monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
|
[
0,
0,
1
] | 2
|
[
0,
0
] |
intervention 1: 600 mg orally once daily for 104 weeks. intervention 2: 180 μg subcutaneous injection once a week for 52 weeks.
|
intervention 1: Telbivudine (LdT) intervention 2: peginterferon alpha-2a
| 1
|
San Francisco | California | United States | -122.41942 | 37.77493
| 0
|
NCT00412750
|
[
3
] | 63
|
RANDOMIZED
|
PARALLEL
| 4SUPPORTIVE_CARE
| 2DOUBLE
| false
| 0ALL
| null |
The purpose of this study is to identify an effective, well tolerated dose and schedule of romiplostim that is appropriate for the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with non-small cell lung cancer receiving gemcitabine and platinum.
| null |
Lung Cancer Chemotherapy-Induced Thrombocytopenia Non-Small Cell Lung Cancer Cancer Lung Neoplasms Oncology Solid Tumors Thrombocytopenia
|
Advanced Non-Small Cell Lung Cancer Chemotherapy Induced Thrombocytopenia CIT NSCLC Stage IIIB NSCLC Stage IV NSCLC Gemcitabine Carboplatin Cisplatin
| null | 4
|
arm 1: Participants received a placebo subcutaneous injection on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice. arm 2: Participants received romiplostim 250 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice. arm 3: Participants received romiplostim 500 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice. arm 4: Participants received romiplostim 750 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice.
|
[
2,
0,
0,
0
] | 5
|
[
2,
0,
0,
0,
0
] |
intervention 1: Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production. intervention 2: Placebo subcutaneous injection. intervention 3: Intravenous infusion intervention 4: Intravenous infusion intervention 5: Intravenous infusion
|
intervention 1: Romiplostim intervention 2: Placebo intervention 3: Gemcitabine intervention 4: Carboplatin intervention 5: Cisplatin
| 113
|
Glendale | Arizona | United States | -112.18599 | 33.53865
Glendale | Arizona | United States | -112.18599 | 33.53865
Anaheim | California | United States | -117.9145 | 33.83529
Anaheim | California | United States | -117.9145 | 33.83529
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Rancho Mirage | California | United States | -116.41279 | 33.73974
Rancho Mirage | California | United States | -116.41279 | 33.73974
Boynton Beach | Florida | United States | -80.06643 | 26.52535
Boynton Beach | Florida | United States | -80.06643 | 26.52535
Vero Beach | Florida | United States | -80.39727 | 27.63864
Vero Beach | Florida | United States | -80.39727 | 27.63864
Athens | Georgia | United States | -83.37794 | 33.96095
Athens | Georgia | United States | -83.37794 | 33.96095
Macon | Georgia | United States | -83.6324 | 32.84069
Macon | Georgia | United States | -83.6324 | 32.84069
Peoria | Illinois | United States | -89.58899 | 40.69365
Peoria | Illinois | United States | -89.58899 | 40.69365
Sioux City | Iowa | United States | -96.40031 | 42.49999
Sioux City | Iowa | United States | -96.40031 | 42.49999
Paducah | Kentucky | United States | -88.60005 | 37.08339
Paducah | Kentucky | United States | -88.60005 | 37.08339
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Baltimore | Maryland | United States | -76.61219 | 39.29038
Baltimore | Maryland | United States | -76.61219 | 39.29038
Sterling Heights | Michigan | United States | -83.0302 | 42.58031
Sterling Heights | Michigan | United States | -83.0302 | 42.58031
Billings | Montana | United States | -108.50069 | 45.78329
Billings | Montana | United States | -108.50069 | 45.78329
Flemington | New Jersey | United States | -74.85933 | 40.51233
Flemington | New Jersey | United States | -74.85933 | 40.51233
Johnson City | New York | United States | -75.95881 | 42.11563
Johnson City | New York | United States | -75.95881 | 42.11563
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Drexel Hill | Pennsylvania | United States | -75.29213 | 39.94706
Drexel Hill | Pennsylvania | United States | -75.29213 | 39.94706
Dunmore | Pennsylvania | United States | -75.63241 | 41.4198
Dunmore | Pennsylvania | United States | -75.63241 | 41.4198
Radnor | Pennsylvania | United States | -75.35991 | 40.04622
Radnor | Pennsylvania | United States | -75.35991 | 40.04622
Columbia | South Carolina | United States | -81.03481 | 34.00071
Columbia | South Carolina | United States | -81.03481 | 34.00071
Germantown | Tennessee | United States | -89.81009 | 35.08676
Germantown | Tennessee | United States | -89.81009 | 35.08676
Austin | Texas | United States | -97.74306 | 30.26715
Austin | Texas | United States | -97.74306 | 30.26715
Houston | Texas | United States | -95.36327 | 29.76328
Houston | Texas | United States | -95.36327 | 29.76328
Houston | Texas | United States | -95.36327 | 29.76328
Graz | N/A | Austria | 15.45 | 47.06667
Graz | N/A | Austria | 15.45 | 47.06667
Innsbruck | N/A | Austria | 11.39454 | 47.26266
Innsbruck | N/A | Austria | 11.39454 | 47.26266
Klagenfurt | N/A | Austria | 14.30528 | 46.62472
Klagenfurt | N/A | Austria | 14.30528 | 46.62472
Linz | N/A | Austria | 14.28611 | 48.30639
Linz | N/A | Austria | 14.28611 | 48.30639
Rankweil | N/A | Austria | 9.64308 | 47.27108
Rankweil | N/A | Austria | 9.64308 | 47.27108
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Sainte-Foy | Quebec | Canada | -71.29217 | 46.78139
Sainte-Foy | Quebec | Canada | -71.29217 | 46.78139
Bad Berka | N/A | Germany | 11.28245 | 50.89982
Bad Berka | N/A | Germany | 11.28245 | 50.89982
Dresden | N/A | Germany | 13.73832 | 51.05089
Dresden | N/A | Germany | 13.73832 | 51.05089
Halle | N/A | Germany | 11.97947 | 51.48158
Halle | N/A | Germany | 11.97947 | 51.48158
Hemer | N/A | Germany | 7.77019 | 51.38707
Hemer | N/A | Germany | 7.77019 | 51.38707
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Edelény | N/A | Hungary | 20.73333 | 48.3
Edelény | N/A | Hungary | 20.73333 | 48.3
Gyula | N/A | Hungary | 21.28333 | 46.65
Gyula | N/A | Hungary | 21.28333 | 46.65
Mátraháza | N/A | Hungary | 19.97981 | 47.87124
Mátraháza | N/A | Hungary | 19.97981 | 47.87124
Pécs | N/A | Hungary | 18.23083 | 46.0725
Pécs | N/A | Hungary | 18.23083 | 46.0725
Székesfehérvár | N/A | Hungary | 18.41034 | 47.18995
Székesfehérvár | N/A | Hungary | 18.41034 | 47.18995
Törökbálint | N/A | Hungary | 18.91356 | 47.42931
Törökbálint | N/A | Hungary | 18.91356 | 47.42931
Zalaegerszeg - Pozva | N/A | Hungary | N/A | N/A
Zalaegerszeg - Pozva | N/A | Hungary | N/A | N/A
Cork | N/A | Ireland | -8.47061 | 51.89797
Cork | N/A | Ireland | -8.47061 | 51.89797
Dublin | N/A | Ireland | -6.24889 | 53.33306
Dublin | N/A | Ireland | -6.24889 | 53.33306
Dublin | N/A | Ireland | -6.24889 | 53.33306
Novara | N/A | Italy | 8.62118 | 45.44694
Novara | N/A | Italy | 8.62118 | 45.44694
Orbassano | N/A | Italy | 7.53813 | 45.00547
Orbassano | N/A | Italy | 7.53813 | 45.00547
Palermo | N/A | Italy | 13.3636 | 38.1166
Palermo | N/A | Italy | 13.3636 | 38.1166
Torino | N/A | Italy | 11.99138 | 44.88856
Torino | N/A | Italy | 11.99138 | 44.88856
Coimbra | N/A | Portugal | -8.41955 | 40.20564
Coimbra | N/A | Portugal | -8.41955 | 40.20564
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Porto | N/A | Portugal | -8.61099 | 41.14961
Porto | N/A | Portugal | -8.61099 | 41.14961
Vila Nova de Gaia | N/A | Portugal | -8.61241 | 41.12401
Vila Nova de Gaia | N/A | Portugal | -8.61241 | 41.12401
| 0
|
NCT00413283
|
[
2,
3
] | 80
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 1FEMALE
| false
|
The study seeks to assess the safety, pharmacodynamics, pharmacokinetics and efficacy of belinostat (PXD101) administered in combination with carboplatin or paclitaxel or both in patients with solid tumours followed by maximum tolerated dose (MTD) expansion (phase II) in ovarian and bladder cancer patients
The clinical trial is now in the MTD (phase II) portion of the study enrolling bladder cancer patients. Enrollment of ovarian patients is complete.
|
MTD Expansion I(Phase II): A total of 18-32 patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin, in need of relapse treatment will be enrolled.
MTD Expansion II (phase II): A total of 15 patients with urothelial (transitional cell) carcinoma of the bladder will be enrolled.
|
Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Bladder Cancer
|
Ovarian cancer Ovarian Neoplasms Primary peritoneal Epithelial ovarian Fallopian tube Bladder cancer belinostat PXD101 mixed mullerian cancer of ovarian origin
| null | 1
|
arm 1: Belinostat: 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: Administered IV 2-3 hours after belinostat infusion on day 3 in a 21-day cycle
Carboplatin: Administered IV infusion after paclitaxel on day 3 in a 21-day cycle
|
[
0
] | 3
|
[
0,
0,
0
] |
intervention 1: None intervention 2: None intervention 3: None
|
intervention 1: belinostat intervention 2: Paclitaxel intervention 3: Carboplatin
| 11
|
Newport Beach | California | United States | -117.92895 | 33.61891
Orlando | Florida | United States | -81.37924 | 28.53834
Covington | Louisiana | United States | -90.10042 | 30.47549
Metairie | Louisiana | United States | -90.15285 | 29.98409
Baltimore | Maryland | United States | -76.61219 | 39.29038
Boston | Massachusetts | United States | -71.05977 | 42.35843
Providence | Rhode Island | United States | -71.41283 | 41.82399
Copenhagen | N/A | Denmark | 12.56553 | 55.67594
Herlev | N/A | Denmark | 12.43998 | 55.72366
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Surrey | N/A | United Kingdom | N/A | N/A
| 0
|
NCT00421889
|
[
4
] | 300
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| null |
The purpose of this 12-week active controlled trial is to evaluate the safety and efficacy of valsartan 80/160/320 mg (weight stratified) compared with enalapril 10/20/40 mg (weight stratified) on sitting systolic blood pressure (SSBP) in 6 - 17 year old children with hypertension (SSBP ≥ 95th percentile for age gender and height).
| null |
Hypertension
|
Children pediatrics High Blood Pressure Hypertension Valsartan enalapril
| null | 6
|
arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None
|
[
0,
0,
0,
1,
1,
1
] | 2
|
[
0,
0
] |
intervention 1: Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg. intervention 2: Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
|
intervention 1: Valsartan intervention 2: Enalapril
| 11
|
East Hanover | New Jersey | United States | -74.36487 | 40.8201
Sites in Belgium | N/A | Belgium | N/A | N/A
Sites in France | N/A | France | N/A | N/A
Sites in Germany | N/A | Germany | N/A | N/A
Hungary | N/A | Hungary | N/A | N/A
Sites in India | N/A | India | N/A | N/A
Sites in Italy | N/A | Italy | N/A | N/A
Poland | N/A | Poland | N/A | N/A
Slovakia | N/A | Slovakia | N/A | N/A
Sites in Sweden | N/A | Sweden | N/A | N/A
Turkey | N/A | Turkey (Türkiye) | N/A | N/A
| 0
|
NCT00433836
|
[
3
] | 60
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| true
|
A multicenter study to compare multiple doses of intravitreal microplasmin for non-surgical PVD induction for treatment of patients with vitreomacular traction.
| null |
Vitreomacular Traction
|
Vitreomacular Traction Maculopathy VMT PVD
| null | 5
|
arm 1: Ocriplasmin 75µg single injection versus sham injection arm 2: Ocriplasmin 125µg single injection versus sham injection arm 3: Ocriplasmin 175µg single injection versus sham injection arm 4: Ocriplasmin 125µg multiple injections. Subjects who did not achieve resolution of VMT by the day 28 visit (i.e. non-responders) were given an open-label injection of ocriplasmin 125µg. Subjects who still did not achieve resolution of VMT by the day 56 visit were given a second open-label injection of ocriplasmin 125µg. arm 5: sham injection
|
[
0,
0,
0,
0,
3
] | 3
|
[
0,
0,
0
] |
intervention 1: Intravitreal injection of ocriplasmin solution containing 75µg of ocriplasmin. intervention 2: Intravitreal injection of ocriplasmin solution containing 125µg of ocriplasmin with up to 2 additional (open label) 125µg ocriplasmin injection at 1 month interval. intervention 3: Intravitreal sham injection
|
intervention 1: ocriplasmin intervention 2: ocriplasmin intervention 3: Sham Comparator
| 4
|
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Ghent | N/A | Belgium | 3.71667 | 51.05
Leuven | N/A | Belgium | 4.70093 | 50.87959
München | N/A | Germany | 13.31243 | 51.60698
| 0
|
NCT00435539
|
[
4
] | 412
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 1FEMALE
| null |
The purpose of this study is to assess the effects of zoledronic acid administered at the same time with teriparatide compared to zoledronic acid alone and teriparatide alone on bone mineral density (BMD) gain in the lumbar spine and total hip
| null |
Osteoporosis
|
Bone Mineral Density (BMD) C-Telopeptides (CTx) dual x-ray absorptiometry (DXA) pro-collagen type 1 N-propeptide (P1NP) teriparatide zoledronic acid Osteoporosis postmenopausal women
| null | 3
|
arm 1: Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks. arm 2: Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. arm 3: Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
|
[
1,
0,
1
] | 3
|
[
0,
0,
0
] |
intervention 1: Zoledronic acid 5.0 mg in a ready-to-infuse plastic bottle with a total fill volume of 103 mL to allow an infusion of 100 mL total volume corresponding to 5 mg of zoledronic acid. intervention 2: Zoledronic acid matched placebo as a 103 mL solution of sterile water (physiologic 0.9% normal saline) to allow an infusion of 100 mL total volume in a ready-to-infuse plastic bottle intervention 3: Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. Each pre-filled delivery device is filled with 3.3 mL to deliver 3 mL.
Each mL contains 250 μg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetate acid, 0.10 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3.0 mg Metacresol, and water for injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4. Each cartridge pre-assembled into a pen device delivers 20 μg of teriparatide per dose each day for up to 28 days.
|
intervention 1: Zoledronic acid intervention 2: Placebo intervention 3: Teriparatide
| 33
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Beverly Hills | California | United States | -118.40036 | 34.07362
La Mesa | California | United States | -117.02308 | 32.76783
Oakland | California | United States | -122.2708 | 37.80437
Colorado Springs | Colorado | United States | -104.82136 | 38.83388
Lakewood | Colorado | United States | -105.08137 | 39.70471
Gainesville | Georgia | United States | -83.82407 | 34.29788
Morton Grove | Illinois | United States | -87.78256 | 42.04059
Urbandale | Iowa | United States | -93.71217 | 41.62666
Bangor | Maine | United States | -68.77265 | 44.79884
Woodbury | Minnesota | United States | -92.95938 | 44.92386
St Louis | Missouri | United States | -90.19789 | 38.62727
Lincoln | Nebraska | United States | -96.66696 | 40.8
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
West Haverstraw | New York | United States | -73.98542 | 41.20954
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Spokane | Washington | United States | -117.42908 | 47.65966
Madison | Wisconsin | United States | -89.40123 | 43.07305
Brussels | N/A | Belgium | 4.34878 | 50.85045
Ghent | N/A | Belgium | 3.71667 | 51.05
Godinne | N/A | Belgium | 4.87364 | 50.34809
Leuven | N/A | Belgium | 4.70093 | 50.87959
Liège | N/A | Belgium | 5.56749 | 50.63373
Essen | N/A | Germany | 7.01228 | 51.45657
Hanover | N/A | Germany | 9.73322 | 52.37052
Heidelberg | N/A | Germany | 8.69079 | 49.40768
Magdeburg | N/A | Germany | 11.62916 | 52.12773
München | N/A | Germany | 13.31243 | 51.60698
Würzburg | N/A | Germany | 9.95121 | 49.79391
Barcelona | N/A | Spain | 2.15899 | 41.38879
Granada | N/A | Spain | -3.60667 | 37.18817
Madrid | N/A | Spain | -3.70256 | 40.4165
Valencia | N/A | Spain | -0.37966 | 39.47391
| 0
|
NCT00439244
|
[
4
] | 180
|
RANDOMIZED
|
FACTORIAL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
General Note: throughout this record, "Rebif® New Formulation" is used for historical and consistency purposes.
Objectives:
Primary: To evaluate the efficacy of Rebif® New Formulation (Interferon-beta-1a \[IFN-beta-1a\], RNF), compared to placebo, in subjects with Relapsing Remitting Multiple Sclerosis and active disease by means of Magnetic Resonance Imaging (MRI) at the end of 16 weeks of treatment Secondary: To evaluate the efficacy of RNF by comparing the mean number of combined unique (CU) lesions per scan per subject between the initial 16 weeks of placebo treatment and 24 weeks of RNF treatment in the same subjects, originally randomized to placebo.
Primary Endpoints: The primary endpoint is the difference between the number of CU active MRI lesions at Week 16 in the RNF group (Group 1) versus the placebo group (Group 2).
Secondary Endpoints: The secondary endpoint is the difference in the mean number of CU active MRI lesions per scan per subject over the following treatment periods: Study Day 1 - Week 16 versus Weeks 17 - 40 for the subjects randomized to Group 2.
| null |
Multiple Sclerosis, Relapsing-Remitting
|
Subjects with relapsing remitting multiple sclerosis
| null | 2
|
arm 1: None arm 2: None
|
[
0,
2
] | 3
|
[
0,
0,
0
] |
intervention 1: RNF will be administered at a dose of 44 mcg subcutaneously three times a week for 40 weeks. intervention 2: Matching placebo will be administered subcutaneously three times a week for 16 weeks. intervention 3: RNF will be administered at a dose of 44 mcg subcutaneously three times a week from Week 17 to Week 40.
|
intervention 1: Rebif® New Formulation (IFN-beta-1a, RNF) intervention 2: Placebo intervention 3: Rebif® New Formulation (IFN-beta-1a, RNF)
| 0
| null | 0
|
NCT00441103
|
[
5
] | 8
|
NON_RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The primary objective of this study is to examine the effect of pramlintide given pre-meal and insulin given just after a meal vs. standard therapy of pre-meal insulin on post-prandial glucose excursions.
The secondary objective is to examine the effect of pramlintide and insulin on glucagon suppression in type 1 diabetes.
|
Following approval by the Institutional Review Board at Baylor College of Medicine 8 adolescents (6 males, 2 females) with type 1 diabetes were recruited to the open-labeled, non-randomized, crossover study. Two male subjects were African American; the remaining subjects were all Caucasian. Six subjects were on insulin pump therapy, and the two on insulin glargine, self-administered at -90minutes. Subjects had their last meal before 12 midnight, and stayed at our research center from 7AM until completion of the study at 2PM. Study A was done before study B.
Basal insulin doses of the subjects were kept constant through studies A and B. No subject was prescribed pramlintide any time in the past prior to participation in this study.
Study A:Insulin therapy was continued as per prescribed home regimen without pramlintide. Subjects self-administered a rapid-acting insulin analog (aspart or lispro) bolus based on their individual insulin: carbohydrate ratio, following which they received 12oz (591ml) of Boost High Protein drink (360 calories, 50gms carbohydrate, 12 gms fat) at 9AM (0 minutes). The Boost was consumed in 5 - 7 minutes. Blood samples were collected for the analysis of blood glucose (BG) levels at -60, -30, -10, and 0 minutes, and every 10 minutes thereafter for the first hour, every 20 minutes for the second hour, and every 30 minutes until the study ended. Blood samples were also collected throughout the study at multiple time points for the analysis of insulin and glucagon levels. Subjects were provided with lunch at 2PM, and discharged.
Study B:The study protocol was identical to study A except 30mcg of pramlintide was administered subcutaneously immediately prior to drinking the Boost at 9AM, and no insulin was given before the meal but was given 15 minutes after the meal (9:15AM) and the dose was reduced by 20%. Study B was conducted within 3 to 4 weeks of study A.
|
Type 1 Diabetes Mellitus
|
pediatric juvenile diabetes mellitus Pediatric type 1 diabetes mellitus
| null | 2
|
arm 1: Insulin therapy was continued as per prescribed home regimen without pramlintide. Subjects self-administered a rapid-acting insulin analog (aspart or lispro) bolus based on their individual insulin: carbohydrate ratio, before meal arm 2: 30mcg of pramlintide was administered subcutaneously immediately prior to the meal and insulin was given 15 minutes after the meal. The dose of insulin was reduced by 20%.
|
[
1,
0
] | 2
|
[
0,
0
] |
intervention 1: Insulin therapy was continued as per prescribed home regimen without pramlintide. Subjects self-administered a rapid-acting insulin analog (aspart or lispro) bolus based on their individual insulin: carbohydrate ratio, before meal. intervention 2: 30mcg of pramlintide was administered subcutaneously immediately prior to the meal and insulin was given 15 minutes after the meal. The dose of insulin was reduced by 20%.
|
intervention 1: Insulin intervention 2: Pramlintide + Insulin
| 1
|
The Bronx | New York | United States | -73.86641 | 40.84985
| 0
|
NCT00442767
|
[
3
] | 14
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
The restoration of endogenous insulin secretion carries significant hopes for shifting the paradigm of life long exogenous insulin therapy in selected groups of patients with type 1 diabetes(T1D). After decades of frustrating clinical attempts, the Edmonton group set up in 2000 new standards for islet transplantation in patients with brittle T1D by achieving insulin independence in 80 percent of patients. These seminal results have however proved much more difficult to duplicate than initially expected.
This single center phase 2 clinical trial, duplicating the Edmonton protocol, is designed for confirming the consistent short term efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with severe T1D.
|
The short term effectiveness of islet transplantation for alleviating hypoglycemia and controlling glucose homeostasis while limiting or even avoiding the nedd for exogenous insulin has been established despite protocol modifications in donor selection, islet preparation or recipient treatment, insulin independence with adequate metabolic control was however rarely prolonged beyond two years. The most frequently proposed explanations include chronic allogenic rejection, recurrence of autoimmunity and beta cell toxicity from administered immunosuppressive drugs.
Fourteen patients were enrolled in this single center phase 2 trial initiated in 2003. Eligible patients were males or females between 18 and 65 years of age, with type 1 diabeted documented for more than 5 years, arginine stimulated C-peptide lower than 0.2ng/ml, and hypoglycemia awareness or documented metabolic lability. Exclusion criteria included body mass index greater than 28Kg/m2, unstable arteriopathy or heart disease, active infection, previous transplantation, insulin daily requirements above 1.2 UI/kg, creatinin clearance below 60 ml/mn/m2 or urinary albumin excretion above 300 mg/day, malignancy, smoking, desire for pregnancy, psychiatric disorders and lack of compliance. The study primary efficacy endpoint was graft survival defined as insulin independence and HbA1c\<6.5%. Secondary outcomes were graft function and metabolic control.
|
Type 1 Diabetes Hypoglycemia Metabolic Diseases
|
diabetes hypoglycemia
| null | 1
|
arm 1: Each participant received up to three sequential fresh islet infusions within three months.
|
[
0
] | 2
|
[
3,
0
] |
intervention 1: Islet transplantation consisted of up to three sequential fresh islet infusions within three months. Access to the portal vein was gained under general anesthesia by percutaneous catheterisation of a peripheral portal branch under ultrasound guidance or by surgical catheterisation of a small mesenteric vein. intervention 2: Immunosuppressive consisted of Tacrolimus, target through level at 3-6 ng/ml, Sirolimus, target through level at 12-15 ng/ml for three months and at 7-10 ng/ml thereafter. A five-dose induction course of Daclizumab 1mg/Kg was administered biweekly beginning one hour prior to the first infusion
|
intervention 1: islet transplantation intervention 2: daclizumab - sirolimus - tacrolimus
| 1
|
Lille | N/A | France | 3.05858 | 50.63297
| 0
|
NCT00446264
|
[
4
] | 44
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
To assess the safety of sildenafil 20 mg TID orally given to Japanese pulmonary arterial hypertension patients (Part 1 and 2) To assess the efficacy after 12 weeks of treatment of sildenafil 20 mg TID orally given to Japanese pulmonary arterial hypertension patients (Part 1)
| null |
Pulmonary Hypertension
|
Pulmonary Arterial Hypertension, PAH
| null | 1
|
arm 1: sildenafil citrate 20 mg TID
|
[
0
] | 1
|
[
0
] |
intervention 1: sildenafil citrate (UK-92,480)
|
intervention 1: sildenafil citrate (UK-92,480)
| 8
|
Chiba | Chiba | Japan | 140.11667 | 35.6
Kanazawa | Ishikawa-ken | Japan | 136.61667 | 36.6
Tsu | Mie-ken | Japan | 136.51667 | 34.73333
Okayama | Okayama-ken | Japan | 133.93333 | 34.65
Hamamatsu | Shizuoka | Japan | 137.73333 | 34.7
Bunkyo-ku | Tokyo | Japan | N/A | N/A
Shinjuku-ku | Tokyo | Japan | N/A | N/A
Tokyo | N/A | Japan | 139.69171 | 35.6895
| 0
|
NCT00454207
|
[
5
] | 15
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
This study will evaluate the efficacy and safety of brimonidine 0.1% three-times daily in patients with glaucoma or ocular hypertension
| null |
Open-angle Glaucoma Ocular Hypertension
| null | 1
|
arm 1: brimonidine 0.1%
|
[
0
] | 1
|
[
0
] |
intervention 1: Brimonidine 0.1%, 1 drop three-times daily for 4 weeks
|
intervention 1: brimonidine 0.1% (Alphagan® P)
| 1
|
San Diego | California | United States | -117.16472 | 32.71571
| 0
|
NCT00457795
|
|
[
4
] | 323
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
Evaluate the efficacy of treatment with Fentanyl Buccal Tablets (FBT) compared with immediate release oxycodone in alleviating breakthrough pain in opioid tolerant patients with chronic pain.
| null |
Chronic Pain
|
Breakthrough pain Opioid-tolerant Chronic pain
| null | 2
|
arm 1: This study includes a screening period, 2 open-label dose titration periods (in randomized order), and 2 double-blind treatment periods (in randomized order). arm 2: This study includes a screening period, 2 open-label dose titration periods (in randomized order), and 2 double-blind treatment periods (in randomized order).
|
[
0,
1
] | 1
|
[
0
] |
intervention 1: Patients will be randomly assigned in a 1:1 ratio either to titrate immediate-release oxycodone first and to titrate FBT second, or to titrate FBT first and immediate-release oxycodone second, followed by 2 double-blind crossover treatment periods (in randomized order). For the double-blind treatment period of the study involving FBT administration, a patient is randomly assigned to receive FBT at the 200, 400, 600, or 800 mcg strength found to be successful during open-label titration. For the double-blind treatment period of the study to which a patient is randomly assigned to receive immediate-release oxycodone, the patient will receive immediate-release oxycodone at the strength (15, 30, 45, or 60 mg) found to be successful during open-label titration.
|
intervention 1: Fentanyl Buccal Tablets Compared With Immediate-Release Oxycodone
| 45
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Birmingham | Alabama | United States | -86.80249 | 33.52066
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Beverly Hills | California | United States | -118.40036 | 34.07362
Duarte | California | United States | -117.97729 | 34.13945
Los Gatos | California | United States | -121.97468 | 37.22661
New Haven | Connecticut | United States | -72.92816 | 41.30815
Jacksonville | Florida | United States | -81.65565 | 30.33218
Orlando | Florida | United States | -81.37924 | 28.53834
Port Orange | Florida | United States | -80.99561 | 29.13832
Sarasota | Florida | United States | -82.53065 | 27.33643
Spring Hill | Florida | United States | -82.52546 | 28.47688
Tampa | Florida | United States | -82.45843 | 27.94752
Atlanta | Georgia | United States | -84.38798 | 33.749
Dawnsonville | Georgia | United States | N/A | N/A
Marietta | Georgia | United States | -84.54993 | 33.9526
Marietta | Georgia | United States | -84.54993 | 33.9526
Evansville | Indiana | United States | -87.55585 | 37.97476
Indianapolis | Indiana | United States | -86.15804 | 39.76838
West Des Moines | Iowa | United States | -93.71133 | 41.57721
Overland Park | Kansas | United States | -94.67079 | 38.98223
Overland Park | Kansas | United States | -94.67079 | 38.98223
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Baltimore | Maryland | United States | -76.61219 | 39.29038
Pikesville | Maryland | United States | -76.72247 | 39.37427
Englewood | New Jersey | United States | -73.97264 | 40.89288
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Durham | North Carolina | United States | -78.89862 | 35.99403
Greensboro | North Carolina | United States | -79.79198 | 36.07264
High Point | North Carolina | United States | -80.00532 | 35.95569
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Columbus | Ohio | United States | -82.99879 | 39.96118
Altoona | Pennsylvania | United States | -78.39474 | 40.51868
Duncansville | Pennsylvania | United States | -78.4339 | 40.42341
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Greenville | South Carolina | United States | -82.39401 | 34.85262
Hendersonville | Tennessee | United States | -86.62 | 36.30477
San Antonio | Texas | United States | -98.49363 | 29.42412
San Antonio | Texas | United States | -98.49363 | 29.42412
Bellevue | Washington | United States | -122.20068 | 47.61038
Charleston | West Virginia | United States | -81.63262 | 38.34982
| 0
|
NCT00463047
|
[
3
] | 7
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| true
| 0ALL
| false
|
The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.
|
Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.
Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.
Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.
There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).
|
Multiple Myeloma
|
multiple myeloma myeloma relapsed myeloma refractory myeloma relapsed, refractory myeloma relapsed, refractory multiple myeloma refractory multiple myeloma relapsed multiple myeloma B lymphoid malignancies Myeloma, Plasma-Cell Myeloma Proteins hnRNP A1 myeloma helix-destabilizing protein, mouse IgC3kappa Jir protein, human gamma 3 myeloma protein Jir, human M-proteins (Myeloma) M315 myeloma protein, mouse myeloma protein M 315, mouse McPC603 antibody myeloma protein McPC603 antibody multiple myeloma M-proteins M protein, multiple myeloma myeloma cell activator myeloma immunoglobulins myeloma immunoglobulin M603 myeloma immunoglobulin S15 myeloma protein A48, mouse A48 myeloma protein, mouse ABPC48 myeloma protein, mouse myeloma protein A 48, mouse myeloma protein Dob myeloma protein M 467 myeloma protein M467 myeloma protein MOPC 141, mouse MOPC141 myeloma protein, mouse myeloma protein MOPC 173 myeloma protein Rou IgA2 myeloma protein Rou myeloma protein TEPC15 myeloma protein T15 myeloma protein TEPC 15 myeloma protein W3129 myeloma protein WIE myeloma-associated membrane antigen KMA myeloma antigen KMA MYEOV protein, human protein 460 myeloma protein MOPC 460 TRAPPC1 protein, human multiple myeloma protein 2, human Wis heavy-chain disease protein, human myeloma protein Wis, human
| null | 1
|
arm 1: Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.
|
[
0
] | 1
|
[
0
] |
intervention 1: Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.
|
intervention 1: Bortezomib
| 1
|
Hackensack | New Jersey | United States | -74.04347 | 40.88593
| 0
|
NCT00464178
|
[
5
] | 334
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
The primary purpose of this trial is to determine if the treatment with rosuvastatin 10 and 20mg/day during 8 weeks in hypertriglyceridemic patients will reduce their triglyceride levels.
| null |
Hypertriglyceridemia Hyperlipoproteinemia Type IV Hyperlipoproteinemia Type V Hyperlipoproteinemia Type IIb Hyperlipidemia
|
Triglycerides hypertriglyceridemia statins rosuvastatin hyperlipoproteinemia Fredrickson Type IIb or IV
| null | 0
| null | null | 1
|
[
0
] |
intervention 1: 10mg or 20mg
|
intervention 1: rosuvastatin
| 3
|
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Mexico City | Mexico City | Mexico | -99.12766 | 19.42847
Monterrey | Nuevo León | Mexico | -100.31721 | 25.68435
| 0
|
NCT00473655
|
[
4
] | 1,700
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 1PREVENTION
| 0NONE
| true
| 1FEMALE
| false
|
This is a non-comparative study. the primary objective of the study is to assess the efficacy of a low dose oral contraceptive in the prevention of pregnancy. The secondary objectives are to assess the incidence of intracyclic bleeding; and to assess the safety and tolerability of the product.
| null |
Contraception
|
Contraception
| null | 1
|
arm 1: 1 tablet per day
|
[
0
] | 1
|
[
0
] |
intervention 1: 1 tablet per day
|
intervention 1: Norethindrone/ethinyl estradiol
| 63
|
Chandler | Arizona | United States | -111.84125 | 33.30616
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Tempe | Arizona | United States | -111.90931 | 33.41477
Tucson | Arizona | United States | -110.92648 | 32.22174
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
Vista | California | United States | -117.24254 | 33.20004
Castle Rock | Colorado | United States | -104.85609 | 39.37221
Denver | Colorado | United States | -104.9847 | 39.73915
Lakewood | Colorado | United States | -105.08137 | 39.70471
Boynton Beach | Florida | United States | -80.06643 | 26.52535
Brooksville | Florida | United States | -82.38991 | 28.55554
Clearwater | Florida | United States | -82.8001 | 27.96585
Gainesville | Florida | United States | -82.32483 | 29.65163
Jacksonville | Florida | United States | -81.65565 | 30.33218
Leesburg | Florida | United States | -81.87786 | 28.81082
Miami | Florida | United States | -80.19366 | 25.77427
Miami | Florida | United States | -80.19366 | 25.77427
Pembroke Pines | Florida | United States | -80.22394 | 26.00315
St. Petersburg | Florida | United States | -82.67927 | 27.77086
West Palm Beach | Florida | United States | -80.05337 | 26.71534
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Decatur | Georgia | United States | -84.29631 | 33.77483
Champaign | Illinois | United States | -88.24338 | 40.11642
Peoria | Illinois | United States | -89.58899 | 40.69365
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Arkansas City | Kansas | United States | -97.03837 | 37.06197
Wichita | Kansas | United States | -97.33754 | 37.69224
Lexington | Kentucky | United States | -84.47772 | 37.98869
Louisville | Kentucky | United States | -85.75941 | 38.25424
Amite | Louisiana | United States | -90.50898 | 30.72657
Marrero | Louisiana | United States | -90.10035 | 29.89937
Chaska | Minnesota | United States | -93.60218 | 44.78941
Berlin | New Jersey | United States | -74.92905 | 39.79123
Edison | New Jersey | United States | -74.4121 | 40.51872
Lawrenceville | New Jersey | United States | -74.7296 | 40.29733
Moorestown | New Jersey | United States | -74.94267 | 39.96706
New York | New York | United States | -74.00597 | 40.71427
Cary | North Carolina | United States | -78.78112 | 35.79154
New Bern | North Carolina | United States | -77.04411 | 35.10849
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Cleveland | Ohio | United States | -81.69541 | 41.4995
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Medford | Oregon | United States | -122.87559 | 42.32652
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Pottstown | Pennsylvania | United States | -75.64963 | 40.24537
Columbia | South Carolina | United States | -81.03481 | 34.00071
Austin | Texas | United States | -97.74306 | 30.26715
Austin | Texas | United States | -97.74306 | 30.26715
Dallas | Texas | United States | -96.80667 | 32.78306
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412
Magna | Utah | United States | -112.10161 | 40.70911
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Salt Lake City | Utah | United States | -111.89105 | 40.76078
West Valley City | Utah | United States | -112.00105 | 40.69161
Norfolk | Virginia | United States | -76.28522 | 36.84681
Richmond | Virginia | United States | -77.46026 | 37.55376
Virginia Beach | Virginia | United States | -75.97799 | 36.85293
| 0
|
NCT00477633
|
[
4
] | 399
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
This study will evaluate the efficacy and safety of Brivaracetam to support the submission file in the indication of adjunctive treatment in adolescents and adults with partial onset seizures.
| null |
Epilepsy
|
Epilepsy Brivaracetam Partial Onset Seizures
| null | 4
|
arm 1: Matching Placebo tablets administered twice a day arm 2: Brivaracetam 20 mg/day, 10 mg administered twice a day arm 3: Brivaracetam 50 mg/day, 25 mg administered twice a day arm 4: Brivaracetam 100 mg/day, 50 mg administered twice a day
|
[
2,
0,
0,
0
] | 4
|
[
10,
0,
0,
0
] |
intervention 1: Daily oral dose of two equal intakes, morning and evening, of Placebo in a double-blinded way for the 12-week Treatment Period intervention 2: Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 20 mg /day in a double-blinded way for the 12-week Treatment Period intervention 3: Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 50 mg /day in a double-blinded way for the 12-week Treatment Period. intervention 4: Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 100 mg /day in a double-blinded way for the 12-week Treatment Period.
|
intervention 1: Placebo intervention 2: Brivaracetam intervention 3: Brivaracetam intervention 4: Brivaracetam
| 76
|
Ghent | N/A | Belgium | 3.71667 | 51.05
La Louvière | N/A | Belgium | 4.18785 | 50.48657
Liège | N/A | Belgium | 5.56749 | 50.63373
Sankt Vith | N/A | Belgium | 6.12724 | 50.28146
Kuopio | N/A | Finland | 27.67703 | 62.89238
Oulu | N/A | Finland | 25.46816 | 65.01236
Seinäjoki | N/A | Finland | 22.82822 | 62.79446
Tampere | N/A | Finland | 23.78712 | 61.49911
Angers | N/A | France | -0.55202 | 47.47156
Béthune | N/A | France | 2.64003 | 50.52965
Bron | N/A | France | 4.91303 | 45.73865
Dijon | N/A | France | 5.01667 | 47.31667
Lille | N/A | France | 3.05858 | 50.63297
Montpellier | N/A | France | 3.87635 | 43.61093
Nancy | N/A | France | 6.18496 | 48.68439
Paris | N/A | France | 2.3488 | 48.85341
Rennes | N/A | France | -1.67429 | 48.11198
Roanne | N/A | France | 4.06802 | 46.03624
Strasbourg | N/A | France | 7.74553 | 48.58392
Bad Berka | N/A | Germany | 11.28245 | 50.89982
Berlin | N/A | Germany | 13.41053 | 52.52437
Bernau | N/A | Germany | 8.0383 | 47.80018
Bielefeld | N/A | Germany | 8.53333 | 52.03333
Freiburg im Breisgau | N/A | Germany | 7.85222 | 47.9959
Kehl-Kork | N/A | Germany | N/A | N/A
Mainz | N/A | Germany | 8.2791 | 49.98419
München | N/A | Germany | 13.31243 | 51.60698
Radeberg | N/A | Germany | 13.91199 | 51.11112
Ulm | N/A | Germany | 9.99155 | 48.39841
Budapest | N/A | Hungary | 19.04045 | 47.49835
Debrecen | N/A | Hungary | 21.62444 | 47.53167
Pécs | N/A | Hungary | 18.23083 | 46.0725
Bangalore | N/A | India | 77.59369 | 12.97194
Bangalore | N/A | India | 77.59369 | 12.97194
Hyderabad | N/A | India | 78.45636 | 17.38405
Jaipur | N/A | India | 75.78781 | 26.91962
Kolkata | N/A | India | 88.36304 | 22.56263
Lucknow | N/A | India | 80.92313 | 26.83928
Mumbai | N/A | India | 72.88261 | 19.07283
Pune | N/A | India | 73.85535 | 18.51957
Pune Maharashtra | N/A | India | N/A | N/A
Bologna | N/A | Italy | 11.33875 | 44.49381
Foggia | N/A | Italy | 15.55188 | 41.45845
Perugia | N/A | Italy | 12.38878 | 43.1122
Roma | N/A | Italy | 11.10642 | 44.99364
Roma | N/A | Italy | 11.10642 | 44.99364
Breda | N/A | Netherlands | 4.77596 | 51.58656
The Hague | N/A | Netherlands | 4.29861 | 52.07667
Zwolle | N/A | Netherlands | 6.09444 | 52.5125
Bialystok | N/A | Poland | 23.16433 | 53.13333
Gdansk | N/A | Poland | 18.64912 | 54.35227
Grodzisk Mazowiecki | N/A | Poland | 20.6337 | 52.10387
Katowice | N/A | Poland | 19.02754 | 50.25841
Katowice | N/A | Poland | 19.02754 | 50.25841
Kielce | N/A | Poland | 20.62752 | 50.87033
Krakow | N/A | Poland | 19.93658 | 50.06143
Lodz | N/A | Poland | 19.47395 | 51.77058
Lublin | N/A | Poland | 22.56667 | 51.25
Poznan | N/A | Poland | 16.92993 | 52.40692
Szczecin | N/A | Poland | 14.55302 | 53.42894
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Alcorcón | N/A | Spain | -3.82487 | 40.34582
Barcelona | N/A | Spain | 2.15899 | 41.38879
Donostia / San Sebastian | N/A | Spain | -1.97499 | 43.31283
Madrid | N/A | Spain | -3.70256 | 40.4165
Vigo | N/A | Spain | -8.72264 | 42.23282
Zaragoza | N/A | Spain | -0.87734 | 41.65606
Biel | N/A | Switzerland | 8.21773 | 46.45587
Geneva | N/A | Switzerland | 6.14569 | 46.20222
Sankt Gallen | N/A | Switzerland | 9.37477 | 47.42391
Tschugg | N/A | Switzerland | 7.08103 | 47.02534
Zurich | N/A | Switzerland | 8.55 | 47.36667
Liverpool | N/A | United Kingdom | -2.97794 | 53.41058
Middlesbrough | N/A | United Kingdom | -1.23483 | 54.57623
| 0
|
NCT00490035
|
[
4
] | 804
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
A study to compare the safety and efficacy of moxifloxacin to ertapenem in patients with intra-abdominal infections.
| null |
Infection
|
Complicated Intra-Abdominal Infections
| null | 2
|
arm 1: Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours. arm 2: Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: Moxifloxacin, 400mg, administered intravenously once daily intervention 2: Active treatment: Ertapenem 1.0g, administered intravenously once daily
|
intervention 1: Moxifloxacin (Avelox, BAY12-8039) intervention 2: Ertapenem intravenous
| 52
|
Ciudadela | Buenos Aires | Argentina | -58.53941 | -34.63787
De Febrero 3 | Buenos Aires | Argentina | N/A | N/A
Merlo | Buenos Aires | Argentina | -58.72744 | -34.66536
San Juan Bautista | Buenos Aires | Argentina | -58.27623 | -34.80896
Buenos Aires | Ciudad Auton. de Buenos Aires | Argentina | -58.37723 | -34.61315
Córdoba | Córdoba Province | Argentina | -64.18853 | -31.40648
Mendoza | Mendoza Province | Argentina | -68.84582 | -32.88946
Rosario | Santa Fe Province | Argentina | -60.63932 | -32.94682
Capital Federal | N/A | Argentina | N/A | N/A
Bruxelles - Brussel | N/A | Belgium | N/A | N/A
Bruxelles - Brussel | N/A | Belgium | N/A | N/A
Ghent | N/A | Belgium | 3.71667 | 51.05
Pleven | N/A | Bulgaria | 24.61667 | 43.41667
Rousse | N/A | Bulgaria | 25.9534 | 43.84872
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Kohtla-Järve | N/A | Estonia | 27.27306 | 59.39861
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tartu | N/A | Estonia | 26.72509 | 58.38062
Amilly | N/A | France | 2.77186 | 47.97281
Besançon | N/A | France | 6.01815 | 47.24878
Heidelberg | Baden-Wurttemberg | Germany | 8.69079 | 49.40768
Beeskow | Brandenburg | Germany | 14.24597 | 52.17291
Hanover | Lower Saxony | Germany | 9.73322 | 52.37052
Paderborn | North Rhine-Westphalia | Germany | 8.75439 | 51.71905
Homburg | Saarland | Germany | 7.33867 | 49.32637
Rio Patras | N/A | Greece | N/A | N/A
Haifa | N/A | Israel | 34.99928 | 32.81303
Kfar Saba | N/A | Israel | 34.90694 | 32.175
Daugavpils | N/A | Latvia | 26.53333 | 55.88333
Liepāja | N/A | Latvia | 21.01085 | 56.50474
Rēzekne | N/A | Latvia | 27.34 | 56.51028
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Valmiera | N/A | Latvia | 25.42751 | 57.54108
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Klaipėda | N/A | Lithuania | 21.13912 | 55.7068
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Brasov | N/A | Romania | 25.60613 | 45.64861
Bucharest | N/A | Romania | 26.10626 | 44.43225
Cluj-Napoca | N/A | Romania | 23.6 | 46.76667
Oradea | N/A | Romania | 21.91833 | 47.0458
Timișoara | N/A | Romania | 21.22571 | 45.75372
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Smolensk | N/A | Russia | 32.04371 | 54.77944
Cape Town | Cape | South Africa | 18.42322 | -33.92584
Pretoria | Gauteng | South Africa | 28.18783 | -25.74486
Somerset West | Western Cape | South Africa | 18.82113 | -34.08401
L'Hospitalet de Llobregat | Barcelona | Spain | 2.10028 | 41.35967
Madrid | Madrid | Spain | -3.70256 | 40.4165
| 0
|
NCT00492726
|
[
4
] | 163
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
To evaluate the long-term, safety of Methylphenidate Transdermal System (MTS) in aged 13-17 years diagnosed withADHD
|
To evaluate the long-term, safety of Methylphenidate Transdermal System (MTS) in the symptomatic treatment of adolescents aged 13-17 years diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. The evaluation of safety will be based on treatment-emergent adverse events (TEAEs), laboratory tests, vital signs, physical examinations, electrocardiograms (ECGs), and skin tolerability to MTS based on the dermal response score (DRS).
|
ADHD
| null | 1
|
arm 1: Methylphenidate Transdermal System
|
[
0
] | 1
|
[
0
] |
intervention 1: One of 4 doses of the MTS transdermal patch over the same duration of wear for approximately 6 months
|
intervention 1: Methylphenidate Transdermal System
| 32
|
Scottsdale | Arizona | United States | -111.89903 | 33.50921
Lafayette | California | United States | -122.11802 | 37.88576
Wildomar | California | United States | -117.28004 | 33.59891
Gainsville | Florida | United States | N/A | N/A
South Miami | Florida | United States | -80.29338 | 25.7076
Roswell | Georgia | United States | -84.36159 | 34.02316
Eagle | Idaho | United States | -116.35401 | 43.69544
Overland Park | Kansas | United States | -94.67079 | 38.98223
Lexington | Kentucky | United States | -84.47772 | 37.98869
Paducah | Kentucky | United States | -88.60005 | 37.08339
Rochester Hills | Michigan | United States | -83.14993 | 42.65837
Troy | Michigan | United States | -83.14993 | 42.60559
Clementon | New Jersey | United States | -74.98294 | 39.8115
Durham | North Carolina | United States | -78.89862 | 35.99403
Fargo | North Dakota | United States | -96.7898 | 46.87719
Minot | North Dakota | United States | -101.29627 | 48.23251
Cleveland | Ohio | United States | -81.69541 | 41.4995
Eugene | Oregon | United States | -123.08675 | 44.05207
Portland | Oregon | United States | -122.67621 | 45.52345
Media | Pennsylvania | United States | -75.38769 | 39.91678
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Providence | Rhode Island | United States | -71.41283 | 41.82399
Memphis | Tennessee | United States | -90.04898 | 35.14953
Austin | Texas | United States | -97.74306 | 30.26715
Bellaire | Texas | United States | -95.45883 | 29.70579
Lubbock | Texas | United States | -101.85517 | 33.57786
San Antonio | Texas | United States | -98.49363 | 29.42412
Burlington | Vermont | United States | -73.21207 | 44.47588
Herndon | Virginia | United States | -77.3861 | 38.96955
Midlothian | Virginia | United States | -77.64916 | 37.50598
Friday Harbor | Washington | United States | -123.01712 | 48.53427
Kirkland | Washington | United States | -122.20874 | 47.68149
| 0
|
NCT00501293
|
|
[
5
] | 445
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
This study will evaluate atomoxetine's efficacy in treating attention-deficit/hyperactivity disorder (ADHD) symptoms and atomoxetine's effect on functional outcomes in young adults.
A gatekeeper strategy will be employed for sequentially testing the secondary objectives.
This study also has an observational community sample arm in which patients will complete all the efficacy measurements via web-based self reporting.
| null |
Attention Deficit Hyperactivity Disorder
| null | 2
|
arm 1: None arm 2: None
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: 20-50 mg, twice a day per by mouth for 12 weeks, followed by up to an additional 12 weeks intervention 2: twice a day, by mouth for 12 weeks
|
intervention 1: Atomoxetine hydrochloride intervention 2: Placebo
| 29
|
Los Angeles | California | United States | -118.24368 | 34.05223
Rolling Hills Est. | California | United States | N/A | N/A
Spring Valley | California | United States | -116.99892 | 32.74477
Wildomar | California | United States | -117.28004 | 33.59891
Gainesville | Florida | United States | -82.32483 | 29.65163
Jacksonville | Florida | United States | -81.65565 | 30.33218
South Miami | Florida | United States | -80.29338 | 25.7076
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Eagle | Idaho | United States | -116.35401 | 43.69544
Topeka | Kansas | United States | -95.67804 | 39.04833
Lexington | Kentucky | United States | -84.47772 | 37.98869
Belmont | Massachusetts | United States | -71.17867 | 42.39593
Farmington Hills | Michigan | United States | -83.37716 | 42.48531
Omaha | Nebraska | United States | -95.94043 | 41.25626
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Piscataway | New Jersey | United States | -74.39904 | 40.49927
New York | New York | United States | -74.00597 | 40.71427
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Beachwood | Ohio | United States | -81.50873 | 41.4645
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Charleston | South Carolina | United States | -79.93275 | 32.77632
Burlington | Vermont | United States | -73.21207 | 44.47588
Woodstock | Vermont | United States | -72.51843 | 43.62424
Midlothian | Virginia | United States | -77.64916 | 37.50598
Seattle | Washington | United States | -122.33207 | 47.60621
Spokane | Washington | United States | -117.42908 | 47.65966
Hato Rey | N/A | Puerto Rico | N/A | N/A
San Juan | N/A | Puerto Rico | -66.10572 | 18.46633
| 0
|
NCT00510276
|
|
[
3
] | 17
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
This 2 arm study will assess the efficacy and safety of Tarceva plus gemcitabine, compared with gemcitabine alone, in the treatment of chemotherapy-naive patients with advanced non-small cell lung cancer. Patients will be randomized to receive either Tarceva 150mg po daily plus gemcitabine on days 1, 8, 15 and every 4 weeks subsequently, or with gemcitabine monotherapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
| null |
Non-Squamous Non-Small Cell Lung Cancer
| null | 2
|
arm 1: Participants received Erlotinib 150 mg/day orally as a continuous schedule with Gemcitabine 1000 (mg/m\^2)/day, IV on Days 1, 8, 15 and every 4 weeks for 6 cycles. arm 2: Participants received Gemcitabine 1000 (mg/m\^2)/day, IV on Days 1, 8, 15 and every 4 weeks for 6 cycles.
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: 150 mg po daily intervention 2: As prescribed
|
intervention 1: Erlotinib intervention 2: Gemcitabine
| 14
|
Auchenflower | N/A | Australia | 152.99213 | -27.47443
Chermside | N/A | Australia | 153.03062 | -27.38472
Footscray | N/A | Australia | 144.9 | -37.8
Greenslopes | N/A | Australia | 153.04951 | -27.50815
Lismore | N/A | Australia | 153.2773 | -28.81354
Melbourne | N/A | Australia | 144.96332 | -37.814
Melbourne | N/A | Australia | 144.96332 | -37.814
Parkville | N/A | Australia | 144.95 | -37.78333
Randwick | N/A | Australia | 151.24895 | -33.91439
Richmond | N/A | Australia | 145.00176 | -37.81819
St Leonards | N/A | Australia | 151.19836 | -33.82344
Sydney | N/A | Australia | 151.20732 | -33.86785
Wodonga | N/A | Australia | 146.88809 | -36.12179
Wollongong | N/A | Australia | 150.89345 | -34.424
| 0
|
NCT00518011
|
|
[
3
] | 20
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
A phase 2 randomized, placebo-controlled, double-blind trial of a two week course of curcuminoids in oral lichen planus will be conducted. 26 consecutive, eligible patients with OLP presenting to the oral medicine clinic at the University of California, San Francisco, will be enrolled. Study subjects will be randomized to receive either placebo or curcuminoids 6000mg/day for 2 weeks in three divided doses of 2000mg three times/day. Measurement of signs, symptoms, periodontal status and blood tests including complete blood count, liver enzymes, serum c reactive protein and serum interleukin-6 levels will be done at baseline and at the end of 2 weeks. A side-effects questionnaire will be administered at the 2-week follow-up.
The Numeric Rating Scale (NRS) will be used to measure symptoms and the Modified Oral Mucositis Index (MOMI) to measure clinical signs of OLP. Primary outcome is change in symptoms from baseline. Secondary outcomes are change in clinical signs, occurrence of side-effects, change in serum C-reactive protein and serum interleukin-6 levels.
| null |
Oral Lichen Planus
|
curcuminoids oral lichen planus c reactive protein interleukin 6
| null | 2
|
arm 1: Curcumin C3 Complex arm 2: Placebo
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Curcuminoids tablets 2000mg three times per day for 12 days intervention 2: None
|
intervention 1: Curcuminoids intervention 2: Placebo
| 1
|
San Francisco | California | United States | -122.41942 | 37.77493
| 0
|
NCT00525421
|
[
0
] | 25
|
RANDOMIZED
|
PARALLEL
| 9OTHER
| 0NONE
| true
| 0ALL
| false
|
Inflammation clearly contributes to the progression of the cystic fibrosis (CF) lung disease, and administration of the anti-inflammatory agent high-dose ibuprofen retards the rate of decline of pulmonary function. However, utilization of this valuable drug has been suboptimal because of its rare, but dramatic, adverse effects. Therefore, alternative anti-inflammatory agents are urgently needed. One strategy for identifying new anti-inflammatory agents is to determine the mechanism by which the only proven anti-inflammatory agent for the CF lung disease, high-dose ibuprofen, exerts its effect. If this were known, then other drugs that act by a similar mechanism become candidates for treating the CF inflammatory disease. The investigators have shown, in our preliminary studies, that high dose ibuprofen limits the delivery of neutrophils to an inflamed mucosal surface, the gingival crevices. The investigators plan to test pioglitazone and simvastatin, (ibuprofen (positive control)) to determine their anti inflammatory affects on neutrophil migration to the oral mucosa.
The hypothesis to be tested is that pioglitazone, and/or simvastatin will reduce neutrophils in the oral mucosa after 10 days of therapy in mouthwashes of healthy volunteers. Ibuprofen will be used as a positive control.
This study will provide pilot data from healthy volunteers to support an FDA Grant to be submitted at a future date.
|
The entire study period for each subject will be 15 days, and consist of 3 periods defined as: Baseline (Day 1,2,3), Treatment (Day 3-10), and Recovery (Day 13-15). Healthy volunteers will be screened on Day 1 (and assessed for eligibility); Eligible subjects will be divided into 3 drug treatment groups pioglitazone, simvastatin and ibuprofen the positive control. The two treatment groups will consist of 4 healthy volunteers who meet the inclusion criteria. There will be 2 healthy volunteers in the positive control group. Group 1 will receive pioglitazone 30 mg once daily, Group 2 will receive simvastatin 40 mg daily and Group 3 the positive control will receive ibuprofen (15-23 mg/kg twice daily, maximum 3200 mg/day) during the Treatment period and serve as the positive control group. This dose is 25% of that prescribed to CF patients. As healthy volunteers are recruited, the first will be assigned to Group 1, the second to Group 2, and so on. After the third subject has been assigned to Group 3, this pattern of assignment will be repeated with subjects 4, 5 and 6, The following 4 healthy volunteers will be assigned to group 1 and 2 (7, 8, 9, 10).
|
Cystic Fibrosis
|
healthy volunteers neutrophil migration anti inflammatory non-steroidal agent simvastatin pioglitazone
| null | 3
|
arm 1: Pioglitazone arm 2: Simvastatin arm 3: Ibuprofen 1000-16-- mg/day, maximum 3200 mg/day
|
[
0,
0,
1
] | 3
|
[
0,
0,
0
] |
intervention 1: 30 mg once a day intervention 2: 40 mg once a day intervention 3: Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day
|
intervention 1: Pioglitazone intervention 2: Simvastatin intervention 3: Ibuprofen
| 2
|
Cleveland | Ohio | United States | -81.69541 | 41.4995
Cleveland | Ohio | United States | -81.69541 | 41.4995
| 0
|
NCT00531882
|
[
5
] | 121
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this study is to evaluate the tolerability and safety of paliperidone ER (extended-release) in doses between 3 milligrams per day and 12 milligrams per day in the treatment of patients with schizophrenia or schizoaffective disorder and liver disease.
|
Patients with schizophrenia or schizoaffective disorder commonly have other conditions that may affect the liver, such as alcohol abuse and/or chronic liver infections (hepatitis). Although single-dose studies in patients with liver disease are conducted to test the safety of medications, there is less information about the safety of treatment with medications for schizophrenia in this at-risk population of patients with schizophrenia or schizoaffective disorder and liver disease. This 9-week study is open-label (both patient and investigators know what study drug and dose of study drug the patient is taking) and has 2 phases. During Phase 1, which lasts 4 weeks, patients will continue to take whatever medication they are already taking for schizophrenia (TAU, or treatment as usual). During the first week of Phase 2, patients will receive decreasing doses of TAU and increasing doses of paliperidone ER. For the rest of Phase 2, which lasts 4 more weeks, patients will take paliperidone ER in doses between 3 mg/day and 12 mg/day, as prescribed by the study doctor. This study will evaluate adverse events and will use several scales and tests to measure the effectiveness of paliperidone ER in patients with an established diagnosis of schizophrenia or schizoaffective disorder and liver disease. Study assessments include the PANSS (Positive and Negative Symptom Scale for Schizophrenia), CGI (Clinical Global Impression scale), MSQ (Medication Satisfaction Questionnaire), sleep VAS (Visual Analog Scale), SF-36 (Short Form 36 Health Survey), and PSP (Personal and Social Performance Scale). Each assessment will be performed at least two times during the course of the study, but some assessments will be done more frequently. Visits are scheduled every 1 to two weeks during the 9 week study.
The hypothesis is that paliperidone ER can be used safely in patients with schizophrenia or schizoaffective disorder who also have identified liver disease. During Phase 1 of the study, patients will continue to take whatever medication they are already taking for schizophrenia (TAU, or treatment as usual) for 4 weeks. For the first week of Phase 2, patients will receive decreasing doses of TAU. During Phase 2, patients will take paliperidone ER in doses between 3 milligrams per day and 12 milligrams per day by mouth for 5 weeks.
|
Schizophrenia Schizoaffective Disorder Psychotic Disorders
|
antipsychotic paliperidone ER liver disease Schizophrenia Schizoaffective Disorder Invega
| null | 1
|
arm 1: Treatment as usual (TAU), Paliperidone ERTreatment as usual is the subject's current antipsychotic and doses for 4 weeks; TAU AND Paliperidone ER - per site investigator for 1 week; Paliperidone ER 6mg once daily for 1 week; Paliperidone ER-3 to 12mg tablets once daily for 4 weeks
|
[
0
] | 1
|
[
0
] |
intervention 1: Treatment as usual is the subject's current antipsychotic and doses for 4 weeks; TAU AND Paliperidone ER - per site investigator for 1 week; Paliperidone ER 6mg once daily for 1 week; Paliperidone ER-3 to 12mg tablets once daily for 4 weeks
|
intervention 1: Treatment as usual (TAU), Paliperidone ER
| 21
|
Cerritos | California | United States | -118.06479 | 33.85835
Chino | California | United States | -117.68894 | 34.01223
Garden Grove | California | United States | -117.94145 | 33.77391
Huntington Beach | California | United States | -117.99923 | 33.6603
Santa Ana | California | United States | -117.86783 | 33.74557
Torrance | California | United States | -118.34063 | 33.83585
Fort Lauderdale | Florida | United States | -80.14338 | 26.12231
Hollywood | Florida | United States | -80.14949 | 26.0112
Kissimmee | Florida | United States | -81.41667 | 28.30468
Lake Charles | Louisiana | United States | -93.2044 | 30.21309
Flowood | Mississippi | United States | -90.13898 | 32.30959
Kansas City | Missouri | United States | -94.57857 | 39.09973
Clementon | New Jersey | United States | -74.98294 | 39.8115
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Staten Island | New York | United States | -74.13986 | 40.56233
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Norristown | Pennsylvania | United States | -75.3399 | 40.1215
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Sioux Falls | South Dakota | United States | -96.70033 | 43.54997
Irving | Texas | United States | -96.94889 | 32.81402
White River Junction | Vermont | United States | -72.31926 | 43.64896
| 0
|
NCT00535145
|
[
3
] | 13
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
RATIONALE: Monoclonal antibodies such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with capecitabine may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with capecitabine work in treating patients with metastatic colorectal cancer.
|
OBJECTIVES:
Primary
* Determine the response rate in patients with metastatic colorectal cancer treated with cetuximab and capecitabine that progressed on prior fluoropyrimidine-containing therapy comprising irinotecan with or without oxaliplatin.
Secondary
* To determine the progression-free survival and overall survival of patients treated with this regimen.
* To determine the tolerance to therapy in these patients.
* To assess biological correlates of response in available tissue biopsies and blood samples.
OUTLINE: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor tissue and blood collection periodically for correlative studies. Samples are analyzed for expression of genes correlated with fluoropyrimidine responsiveness via quantitation RT-PCR; degree of expression of EGFR via immunohistochemistry; and expression pattern analysis via gene expression profiling and polymorphism.
After completion of study treatment, patients are followed periodically.
|
Colorectal Cancer
|
recurrent colon cancer stage IV colon cancer recurrent rectal cancer stage IV rectal cancer
| null | 1
|
arm 1: Cetuximab 400mg/m2 IV on day 1 over 2 hours then 250 mg/m2 over 1 hour weekly + Xeloda(Capecitabine) 1000mg/m2 BID on days 1-14 repeated every 21 days.
|
[
0
] | 7
|
[
2,
0,
6,
6,
6,
6,
10
] |
intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None
|
intervention 1: cetuximab intervention 2: capecitabine intervention 3: gene expression analysis intervention 4: microarray analysis intervention 5: polymorphism analysis intervention 6: reverse transcriptase-polymerase chain reaction intervention 7: immunohistochemistry staining method
| 2
|
Duarte | California | United States | -117.97729 | 34.13945
Pasadena | California | United States | -118.14452 | 34.14778
| 0
|
NCT00538291
|
[
0
] | 25
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
Age-related macular degeneration, a leading cause of blindness, is caused by an abnormal growth of the vessels beneath the retina. Ranibizumab (Lucentis) is a new drug that inhibits the growth of new vessels and has recently been approved by FDA for treating this condition. This study is carried out to evaluate the changes in retinal function after an injection of ranibizumab.
|
The functional changes of the retina can be recorded by an electroretinography (ERG).
|
Age-related Macular Degeneration
|
age-related macular degeneration (AMD) choroidal neovascularization membrane(CNVM) ranibizumab anti-vascular endothelial growth factor electrophysiology electroretinography
| null | 0
| null | null | 1
|
[
0
] |
intervention 1: A single dose of 0.5 mg ranibizumab injected intravitreally.
|
intervention 1: ranibizumab
| 1
|
Hat Yai | Changwat Songkhla | Thailand | 100.47668 | 7.00836
| 0
|
NCT00539734
|
[
4
] | 343
|
RANDOMIZED
|
PARALLEL
| 1PREVENTION
| 4QUADRUPLE
| false
| 0ALL
| false
|
The purpose of this study is to assess the efficacy of esomeprazole (D961H) 20 mg versus placebo once daily for up to 24 weeks of treatment involving patients with a history of gastric and/or duodenal ulcers receiving daily nonsteroidal anti-inflammatory drug (NSAID) therapy by evaluating presence or absence of gastric and/or duodenal ulcers throughout the treatment period (24 weeks) in terms of efficacy on prevention of gastric and/or duodenal ulcers
| null |
Gastric Ulcer Duodenal Ulcer Rheumatoid Arthritis Osteoarthritis Lumbago
|
gastrointestinal GI NSAID Japan Japanese Gastric ulcer duodenal ulcer
| null | 2
|
arm 1: Placebo arm 2: Esomeprazole 20 mg
|
[
2,
0
] | 2
|
[
0,
0
] |
intervention 1: 20mg once daily oral intervention 2: once daily oral
|
intervention 1: Esomeprazole intervention 2: Placebo
| 39
|
Chiryū | Aichi-ken | Japan | 137.03333 | 35.0
Seto | Aichi-ken | Japan | 137.1 | 35.23333
Yotukaido | Chiba | Japan | N/A | N/A
Miyaodai | Fukuoka | Japan | 130.71276 | 33.84661
Sapporo | Hokkaido | Japan | 141.35 | 43.06667
Akashi | HYOGOi | Japan | 135.00687 | 34.65524
Itami | Hyōgo | Japan | 135.40126 | 34.78427
Koto | Hyōgo | Japan | N/A | N/A
Nishinomiya | Hyōgo | Japan | 135.33199 | 34.71562
Hitachi | Ibaragi | Japan | 140.65 | 36.6
Morioka | Iwate | Japan | 141.15 | 39.7
Sagamihara | Kanagawa | Japan | 139.24167 | 35.56707
Yokohama | Kanagawa | Japan | 139.65 | 35.43333
Kōtari | Kyoto | Japan | 135.70547 | 34.92097
Kyoto | Kyoto | Japan | 135.75385 | 35.02107
Chiisagata | Nagano | Japan | N/A | N/A
Matsumoto | Nagano | Japan | 137.96667 | 36.23333
Nagano | Nagano | Japan | 138.18333 | 36.65
Sasebo | Nagasaki | Japan | 129.72502 | 33.16834
Beppu | Oita Prefecture | Japan | 131.49751 | 33.27945
Ōita | Oita Prefecture | Japan | 131.6 | 33.23333
Ibara | Okayama-ken | Japan | 133.46667 | 34.6
Hirakata | Osaka | Japan | 135.64914 | 34.81352
Osaka | Osaka | Japan | 135.50107 | 34.69379
Sakai | Osaka | Japan | 135.46653 | 34.58216
Suita | Osaka | Japan | 135.51567 | 34.76143
Takatsuki | Osaka | Japan | 135.61678 | 34.84833
Kawagoe | Saitama | Japan | 139.48528 | 35.90861
Saitama | Saitama | Japan | 139.65657 | 35.90807
Fukuroi | Shizuoka | Japan | 137.91667 | 34.75
Hamamatsu | Shizuoka | Japan | 137.73333 | 34.7
Izunokuni | Shizuoka | Japan | 138.95143 | 35.03907
Maikinohara | Shizuoka | Japan | N/A | N/A
Shizuoka | Shizuoka | Japan | 138.38333 | 34.98333
Yaizu | Shizuoka | Japan | 138.31952 | 34.86877
Shimotsuke | Tochigi | Japan | 139.86622 | 36.41323
Chiyoda City | Tokyo | Japan | 139.75056 | 35.68449
Koto | Tokyo | Japan | N/A | N/A
Musashimurayama | Tokyo | Japan | 139.42635 | 35.74242
| 0
|
NCT00542789
|
[
4
] | 52
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
To investigate the plasma drug level, efficacy, and safety of 7-day repeated oral administration of OPC-41061 at 15 mg/day (treatment period 1) and subsequent 7-day repeated administration of OPC-41061 at 15 mg/day or 30 mg/day if diuretic effect is insufficient (treatment period 2) in congestive heart failure (CHF) patients with extracellular volume expansion despite conventional diuretic therapy.
| null |
Cardiac Edema
|
Vasopressin antagonist , Cardiac Edema ,Diuretics
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: 15-30mg/day,daily for 14days
|
intervention 1: OPC-41061 （Tolvaptan)
| 6
|
Chubu Region | N/A | Japan | N/A | N/A
Hokkaido Region | N/A | Japan | N/A | N/A
Kanto Region | N/A | Japan | N/A | N/A
Kinki Region | N/A | Japan | N/A | N/A
Kyuush | N/A | Japan | N/A | N/A
Shikoku Region | N/A | Japan | N/A | N/A
| 0
|
NCT00544869
|
[
4
] | 947
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 2MALE
| null |
To evaluate the efficacy and safety of fesoterodine on overactive bladder symptom improvement when added to ongoing alpha blocker treatment.
| null |
Overactive Bladder Syndrome
| null | 2
|
arm 1: None arm 2: None
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Fesoterodine 4mg or 8mg intervention 2: Placebo
|
intervention 1: Fesoterodine intervention 2: Placebo
| 137
|
Birmingham | Alabama | United States | -86.80249 | 33.52066
Gilbert | Arizona | United States | -111.78903 | 33.35283
Gilbert | Arizona | United States | -111.78903 | 33.35283
Litchfield Park | Arizona | United States | -112.35794 | 33.49337
Mesa | Arizona | United States | -111.82264 | 33.42227
Phoenix | Arizona | United States | -112.07404 | 33.44838
Tucson | Arizona | United States | -110.92648 | 32.22174
La Mesa | California | United States | -117.02308 | 32.76783
Newport Beach | California | United States | -117.92895 | 33.61891
San Bernardino | California | United States | -117.28977 | 34.10834
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
Aurora | Colorado | United States | -104.83192 | 39.72943
Denver | Colorado | United States | -104.9847 | 39.73915
Jupiter | Florida | United States | -80.09421 | 26.93422
Orange City | Florida | United States | -81.29867 | 28.94888
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Dunwoody | Georgia | United States | -84.33465 | 33.94621
Evansville | Indiana | United States | -87.55585 | 37.97476
Jeffersonville | Indiana | United States | -85.73718 | 38.27757
Newburgh | Indiana | United States | -87.40529 | 37.94449
Des Moines | Iowa | United States | -93.60911 | 41.60054
Iowa City | Iowa | United States | -91.53017 | 41.66113
Baltimore | Maryland | United States | -76.61219 | 39.29038
Owings Mills | Maryland | United States | -76.78025 | 39.41955
Watertown | Massachusetts | United States | -71.18283 | 42.37093
Flint | Michigan | United States | -83.68746 | 43.01253
Saint Clair Shores | Michigan | United States | -82.88881 | 42.49698
Troy | Michigan | United States | -83.14993 | 42.60559
Utica | Michigan | United States | -83.03354 | 42.62614
West Bloomfield | Michigan | United States | -83.38356 | 42.56891
West Bloomfield | Michigan | United States | -83.38356 | 42.56891
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Omaha | Nebraska | United States | -95.94043 | 41.25626
Sewell | New Jersey | United States | -75.14434 | 39.7665
Albany | New York | United States | -73.75623 | 42.65258
Garden City | New York | United States | -73.6343 | 40.72677
Kingston | New York | United States | -73.99736 | 41.92704
New York | New York | United States | -74.00597 | 40.71427
Poughkeepsie | New York | United States | -73.92097 | 41.70037
Syracuse | New York | United States | -76.14742 | 43.04812
Williamsville | New York | United States | -78.73781 | 42.96395
Durham | North Carolina | United States | -78.89862 | 35.99403
Greensboro | North Carolina | United States | -79.79198 | 36.07264
Fargo | North Dakota | United States | -96.7898 | 46.87719
Fargo | North Dakota | United States | -96.7898 | 46.87719
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Columbus | Ohio | United States | -82.99879 | 39.96118
Columbus | Ohio | United States | -82.99879 | 39.96118
Bethany | Oklahoma | United States | -97.63226 | 35.51867
Portland | Oregon | United States | -122.67621 | 45.52345
Bala-Cynwyd | Pennsylvania | United States | -75.23407 | 40.00761
Camp Hill | Pennsylvania | United States | -76.91997 | 40.23981
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Charleston | South Carolina | United States | -79.93275 | 32.77632
Greer | South Carolina | United States | -82.22706 | 34.93873
Austin | Texas | United States | -97.74306 | 30.26715
Austin | Texas | United States | -97.74306 | 30.26715
Houston | Texas | United States | -95.36327 | 29.76328
Tacoma | Washington | United States | -122.44429 | 47.25288
Madison | Wisconsin | United States | -89.40123 | 43.07305
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Edegem | N/A | Belgium | 4.44504 | 51.15662
Leuven | N/A | Belgium | 4.70093 | 50.87959
Salvador | Estado de Bahia | Brazil | -38.49096 | -12.97563
Curitiba | Paraná | Brazil | -49.27306 | -25.42778
Rio de Janeiro | Rio de Janeiro | Brazil | -43.18223 | -22.90642
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
Campos do Jordão | São Paulo | Brazil | -45.59139 | -22.73944
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
Victoria | British Columbia | Canada | -123.35155 | 48.4359
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Barrie | Ontario | Canada | -79.66634 | 44.40011
North Bay | Ontario | Canada | -79.46633 | 46.3168
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Chicoutimi | Quebec | Canada | -71.06369 | 48.41963
Pointe-Claire | Quebec | Canada | -73.81669 | 45.44868
Sherbrooke | Quebec | Canada | -71.89908 | 45.40008
Medellín | Antioquia | Colombia | -75.57151 | 6.245
Bogota | Cundinamarca | Colombia | N/A | N/A
Berlin | N/A | Germany | 13.41053 | 52.52437
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Göttingen | N/A | Germany | 9.93228 | 51.53443
Hagenow | N/A | Germany | 11.19159 | 53.43134
Lauenburg | N/A | Germany | 10.55654 | 53.37199
Leipzig | N/A | Germany | 12.37129 | 51.33962
Oberursel | N/A | Germany | 8.57747 | 50.20731
Wiesbaden | N/A | Germany | 8.24932 | 50.08258
Ioannina | Ipiros | Greece | 20.85189 | 39.66486
Pátrai | N/A | Greece | 21.73444 | 38.24444
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
New Delhi | New Delhi | India | 77.2148 | 28.62137
Ludhiana | Punjab | India | 75.85379 | 30.91204
Lucknow | Uttar Pradesh | India | 80.92313 | 26.83928
Lucknow | Uttar Pradesh | India | 80.92313 | 26.83928
Kuching | Sarawak | Malaysia | 110.33333 | 1.55
Kuching | Sarawak | Malaysia | 110.33333 | 1.55
Roermond | N/A | Netherlands | 5.9875 | 51.19417
Tilburg | N/A | Netherlands | 5.0913 | 51.55551
Zutphen | N/A | Netherlands | 6.20139 | 52.13833
Bodø | N/A | Norway | 14.37513 | 67.28267
Oslo | N/A | Norway | 10.74609 | 59.91273
Cebu City | Cebu | Philippines | 123.89071 | 10.31672
Quezon City | Philippines | Philippines | 121.0509 | 14.6488
Bacolod City | N/A | Philippines | 122.95 | 10.66667
Makati City | N/A | Philippines | 121.03269 | 14.55027
Manila | N/A | Philippines | 120.9822 | 14.6042
Manila | N/A | Philippines | 120.9822 | 14.6042
Bialystok | N/A | Poland | 23.16433 | 53.13333
Gdansk | N/A | Poland | 18.64912 | 54.35227
Gdansk | N/A | Poland | 18.64912 | 54.35227
Lodz | N/A | Poland | 19.47395 | 51.77058
Mysłowice | N/A | Poland | 19.16668 | 50.20745
Wroclaw | N/A | Poland | 17.03333 | 51.1
Singapore | Singapore | Singapore | 103.85007 | 1.28967
Singapore | Singapore | Singapore | 103.85007 | 1.28967
Bratislava | Slovakia | Slovakia | 17.10674 | 48.14816
Martin | Slovakia | Slovakia | 18.92399 | 49.06651
Piešťany | Slovakia | Slovakia | 17.82591 | 48.59479
Banská Bystrica | N/A | Slovakia | 19.15349 | 48.73946
Skalica | N/A | Slovakia | 17.22635 | 48.8449
Bucheon-si | Gyunggi-do | South Korea | 126.78306 | 37.49889
Pusan | N/A | South Korea | 128.3681 | 36.3809
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Martorell | Barcelona | Spain | 1.93062 | 41.47402
Getafe | Madrid | Spain | -3.73295 | 40.30571
Manacor | Palma de Mallorca | Spain | 3.20955 | 39.56964
Borås | N/A | Sweden | 12.9401 | 57.72101
Jönköping | N/A | Sweden | 14.15618 | 57.78145
Skövde | N/A | Sweden | 13.84506 | 58.39118
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Ratchathewi | Bangkok | Thailand | 100.53358 | 13.759
Amphoe Mueang | Chiang Mai | Thailand | N/A | N/A
| 0
|
NCT00546637
|
|
[
5
] | 551
| null |
PARALLEL
| 0TREATMENT
| null | false
| 0ALL
| null |
German stroke units are hesitating to use Aggrenox for secondary ischaemic stroke / transient ischaemic attack (TIA) prevention in a sub-acute treatment setting. They argue that clinical experience with sub-acute Aggrenox treatment is limited and poorly documented when compared with sub-acute acetylsalicylic acid (ASA) treatment. However, long term treatment (started after 3-6 months after stroke/TIA) with Aggrenox was safe and superior to ASA treatment in preventing recurrent strokes. There is no evidence for ASA to prevent from neurological progression after stroke during the first 3 months. Results from a cohort study suggest that starting Aggrenox within 72 hours after stroke predicts clinical improvement in the National Institute of Health Stroke Scale (NIHSS) at discharge from the hospital. Dipyridamole suppresses acute inflammatory responses to stroke.
This study is designed to investigate the tolerability and efficacy of a secondary stroke prevention treatment with Aggrenox when initiated within 24 hours of stroke onset on a stroke unit compared to later initiation after a 7 day ASA treatment and outside off a stroke unit setting.
| null |
Cerebrovascular Accident
| null | 0
| null | null | 2
|
[
0,
0
] |
intervention 1: None intervention 2: None
|
intervention 1: Aggrenox bid (ASA 25mg/Dipyridamole ER 200mg) intervention 2: ASA 100 mg qd
| 1
|
Bad Homburg | N/A | Germany | 8.61816 | 50.22683
| 0
|
NCT00562588
|
|
[
0
] | 71
|
RANDOMIZED
|
PARALLEL
| 1PREVENTION
| 0NONE
| false
| 1FEMALE
| false
|
Many women choose Depo-Provera for birth control because it is easy to use and very effective. However, a significant number of Depo-Provera users experience irregular bleeding during the first 90 days. Many users discontinue after their first injection due to irregular bleeding. This study will evaluate the effect of using an estrogen vaginal ring during the first 90 days of Depo-Provera use to see if it is acceptable to women and whether it decreases irregular bleeding during the first 90 days of use and increases continuation to a second injection.
|
Many women choose depot medroxyprogesterone acetate (DMPA) for contraception because it is long-acting, highly effective, and requires minimal user involvement. One of the most common side effects of DMPA use during the first 90 day cycle is irregular bleeding. There are few studies that report mean number of bleeding days among DMPA users. A large World Health Organization (WHO) trial including ten international centers and menstrual data on 748 women using DMPA including 372 woman-years of follow-up reported 23.6 mean days of spotting and bleeding during the first cycle with a standard deviation of 18.9 days (WHO). Another study sponsored by WHO (n=575) reported that 25% of subjects had bleeding/spotting episodes during the first cycle of DMPA that exceeded 13 days. The number of bleeding/spotting days and number of bleeding/spotting episodes decreased over successive reference periods (Said 1987).
Discontinuation rates are high after the first injection and related to irregular bleeding. Rates of discontinuation after the first injection range from 15-60% but were around 30% in most studies (Harel, Paul, Polaneczy, Lim, Hubacher, Sangi, Rickert). Several studies noted that the largest percentage of discontinuation during the first year of DMPA use occurs after the first injection (Rickert, Hubacher, Lim). Irregular bleeding is uniformly cited as one of the most common reasons for discontinuation, accounting for 17-60% of all reasons given (Harel, Paul, Polaneczy, Lim, Sangi). An intervention to prevent or minimize irregular bleeding during the first 90 days of DMPA use could potentially minimize or prevent this bothersome side effect and thus improve continuation.
Few studies have examined the effect of prophylactic or therapeutic estrogen supplementation on irregular bleeding in DMPA users. A randomized trial (n=132) of cyclic transdermal estradiol 0.1 mg/day (Climara) for 3 months versus placebo in women initiating DMPA immediately post-abortion showed no difference in continuation rates at 12 months; however, the authors of this study reported a high rate of non-compliance with the study protocol and lacked an adequate sample size to detect a difference (Goldberg). This is the only study to report on prophylactic estrogen supplementation in DMPA users.
Two studies evaluated therapeutic estrogen supplementation in DMPA users. In 1996, WHO published results of a trial in which women using DMPA and experiencing a bleeding episode greater than 7 days during the first or second injection interval were offered treatment. Subjects (n=278) were randomized to a 14 day course of 50 mcg ethinyl estradiol, 2.5 mg oestrone sulphate, or placebo. The authors found that subjects treated with ethinyl estradiol had shorter median time to cessation of bleeding and fewer bleeding/spotting days (Said 1996). An observational study (n=131) of adolescents reporting vaginal bleeding on DMPA who were treated with monophasic oral contraceptive pills identified improvement of bleeding patterns and a high rate of continuation in those receiving treatment (Rager).
Estrogen supplementation appears to be more effective than placebo in stopping and decreasing bleeding in Norplant users. Women who presented with a spontaneous complaint of prolonged or irregular bleeding were randomly assigned to receive 20 days of treatment with a combined oral contraceptive, 50 mcg ethinyl estradiol, or placebo. Both combined oral contraceptive pills and estradiol were significantly more effective than placebo in stopping bleeding and decreasing the mean number of bleeding days during treatment (Alvarez).
To summarize, prior studies have not identified an acceptable or effective prophylactic intervention to prevent or minimize irregular bleeding or improve continuation rates in DMPA users. The first cycle of DMPA is a critical time for such an intervention. Our study will evaluate estrogen supplementation with an estrogen vaginal ring during the first 90 days of DMPA use versus no estrogen supplementation and report on acceptability, bleeding patterns, and continuation rates. Femring®, an estradiol vaginal ring currently used for treatment of postmenopausal symptoms, provides 100 mcg of estradiol per day with one ring designed for 90 days of consecutive use. This dose provides systemic levels sufficient to suppress vasomotor symptoms in postmenopausal women (Speroff). The vaginal ring would require minimal user involvement when placed at the time of DMPA initiation. If acceptable and effective, this intervention could prevent or minimize irregular bleeding and improve continuation rates of this highly effective contraceptive method.
|
Metrorrhagia
|
Depo-Provera Medroxyprogesterone Acetate Metrorrhagia Irregular Bleeding
| null | 2
|
arm 1: Subjects will receive an estrogen vaginal ring (100 mcg) during the first 90 days of Depo-Provera use. arm 2: Subjects will receive Depo-Provera intramuscular injection.
|
[
0,
5
] | 2
|
[
0,
0
] |
intervention 1: Estrogen vaginal ring (100 mcg) placed for the first 90 days of Depo-Provera use.
Femring® (estradiol acetate vaginal ring) is a flexible off-white ring designed for vaginal insertion with measurements that include an outer diameter of 56 mm, cross-sectional diameter of 7.6 mm, and core diameter of 2 mm. Femring® 0.1 mg/day has a central core containing 24.8 mg of estradiol acetate which releases at a rate equivalent to 0.1 mg of estradiol per day for 3 months. intervention 2: Medroxyprogesterone intramuscular injection comes as a suspension (liquid) to be injected into the buttocks or upper arm. It is usually given once every 3 months (13 weeks), and the recommended dose is 150 mg.
|
intervention 1: Femring® intervention 2: DepoProvera ®
| 1
|
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT00563576
|
[
3
] | 3
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with rituximab may be an effective treatment for multiple myeloma.
PURPOSE: This phase II trial is studying the side effects of giving lenalidomide together with rituximab and to see how well it works in treating patients with recurrent or refractory multiple myeloma.
|
OBJECTIVES:
Primary
* To determine the safety and efficacy, as determined by response rate (complete response \[CR\] + near CR + partial response), of lenalidomide administered with rituximab in patients with relapsed and/or refractory CD20+ multiple myeloma.
Secondary
* To assess the effects of this regimen on patient lymphocyte subsets (T, B, and NK cells) in peripheral blood and bone marrow samples from these patients.
* To perform detailed phenotypic analyses of NK cells in patient blood and bone marrow samples at baseline and post-treatment.
OUTLINE: Patients receive oral lenalidomide once daily on days 1-21. Treatment with lenalidomide repeats every 28 days for at least 4 courses. Patients also receive rituximab IV once weekly in weeks 2-5 and in week 13. Patients with stable disease then receive rituximab once every 8 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Peripheral blood samples are collected at baseline, and after courses 2 and 4. Samples are examined by flow cytometry for lymphocyte subset analysis (T-, B-, and NK-cell percentages and absolute numbers) and NK-cell phenotyping (CD16, CD56, NKG2D expression). Samples are also examined by immunologic assays of isolated peripheral blood mononuclear cells. Bone marrow aspirate samples are also collected at baseline and after course 2. Bone marrow mononuclear cells are isolated and evaluated by CD138+ plasma cell selection, ex vivo antibody-dependent cellular cytotoxicity assays, and bone marrow lymphocyte subset analysis.
After completion of study therapy, patients are followed at 30 days.
|
Multiple Myeloma and Plasma Cell Neoplasm
|
refractory multiple myeloma
| null | 1
|
arm 1: This study will employ a Simon optimal two-stage design. Patients will receive lenalidomide 25 mg daily for days 1-21 of each 28 day cycle. Rituximab 375 mg/m2 will be given weekly for 4 weeks beginning 1 week after the start of lenalidomide therapy (weeks 2-5), and then once 8 weeks later (week 13). Patients with stable disease or better after 4 cycles (week 16, in the absence of delays for toxicity) will be able to continue on therapy on the same lenalidomide schedule and with rituximab 375 mg/m2 given once every 8 weeks.
|
[
0
] | 5
|
[
2,
0,
6,
10,
10
] |
intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None
|
intervention 1: rituximab intervention 2: lenalidomide intervention 3: microarray analysis intervention 4: flow cytometry intervention 5: laboratory biomarker analysis
| 1
|
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT00567229
|
[
5
] | 50
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 1SINGLE
| false
| 0ALL
| true
|
This study will evaluate the relative effectiveness of risperidone Consta injections occurring every 2 weeks in contrast to treatment as usual in preventing symptomatic relapse and rates of rehospitalization or admission into respite care for bipolar patients.
Hypothesis: Risperdal Consta injections every 2 weeks will reduce the number of symptomatic relapses into mania, hypomania, mixed state, or depression, as shown by key indicators that include symptomatic relapse, rehospitalizations, emergency or urgent care visits, respite care, and intensive outpatient treatment as compared to treatment as usual.
|
Bipolar disorder arguably represents the most difficult to treat of all psychiatric disorders. In fact, long-term stabilization is more the exception than the rule, and the majority of patients experience frequent relapses of illness. Studies have shown that both bipolar I and II patients spend about half of their weeks in a significant symptomatic state. Relapses and persistent illness result in substantial morbidity, mortality, and disability.
Symptomatic recurrences happen as a result of breakthrough symptoms during active treatment and intermittent non-adherence. Therefore, enhanced control of symptoms, coupled with ensured adherence, is very likely to improve the long-term outcome of this difficult-to-treat condition.
Risperidone has been shown to be effective in controlling symptoms of acute mania or mixed state in two registration monotherapy and one combination treatment study with lithium or valproate, as well as several smaller trials. However, longer-term treatment studies are relatively lacking. As well, although Risperdal Consta(TM) has been shown to be of benefit in prevention of relapse in patients with schizophrenia, relatively little longer-term data in bipolar disorder is available. Nonetheless, both risperidone and Risperdal Consta (TM) are likely to be highly efficacious for the maintenance prevention of relapse in bipolar disorder. Moreover, Risperdal Consta(TM) helps to ensure longer-term treatment effectiveness, both by better adherence and improved control of symptoms. The present study is intended to determine whether Risperdal Consta(TM) injections, added to ongoing pharmacotherapy, will improve outcome relative to treatment as usual.
|
Bipolar Disorder
|
Bipolar Disorder Depression, Bipolar Mania
| null | 2
|
arm 1: Risperdal Consta injection in conjunction with existing treatment arm 2: Clinician and patient decide upon treatment, as in a non-research clinical setting. The only treatment exclusion is any form of risperidone.
|
[
0,
1
] | 2
|
[
0,
0
] |
intervention 1: Risperdal Consta (TM) will be administered every 2 weeks by deep intramuscular (IM) gluteal injection, by a trained health care professional. Injections will alternate between the two buttocks. The initial dose will be 25 mg IM every 2 weeks. A minimum dose of 25 mg. every 2 weeks will be maintained. At the clinician's discretion, the dose may be advanced to 37.5 mg. or 50 mg. In addition, the dose will be raised to 37.5 mg. or 50 mg. if the following conditions remain: (1) Young Mania Rating Scale (YMRS) score \> 12; or (2) Evidence of impending relapse; and no dose limiting side effect. If the 25 mg. dose is not tolerated, the dose can be held temporarily; however, attempts will be made to achieve and maintain the dose at 25 mg. (or higher) until the end of the study period. intervention 2: Treatment was provided in this arm based solely on the choice of the treatment provider and participant. Treatment providers were not part of the study staff and were completely free to make treatment choices except that they were not allowed to select a long-acting injectible.
|
intervention 1: Risperdal (risperidone) Consta intervention 2: Treatment as usual
| 1
|
Nashville | Tennessee | United States | -86.78444 | 36.16589
| 0
|
NCT00571688
|
[
5
] | 13
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 1FEMALE
| false
|
The purpose of this trial is to compare the difference in bone microarchitecture of the distal radius at month 12 in postmenopausal osteopenic women treated with risedronate 150mg taken once a month compared to placebo.
| null |
Osteoporosis
| null | 2
|
arm 1: one 150 mg risedronate once a month, orally arm 2: Placebo tablet once a month, orally
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: oral tablet once a month for 12 months intervention 2: tablet, 150 mg once a month for 12 months
|
intervention 1: placebo intervention 2: risedronate
| 4
|
Tuscon | Arizona | United States | N/A | N/A
Omaha | Nebraska | United States | -95.94043 | 41.25626
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
| 0
|
NCT00577395
|
|
[
0
] | 44
|
RANDOMIZED
|
PARALLEL
| null | 3TRIPLE
| false
| 0ALL
| true
|
Subjects participating in this protocol will participate in three phases: 1) pre-admission, 2) inpatient admission, and 3) follow-up. Pre-admission involves screening (detailed in inclusion/exclusion criteria section) and one week of outpatient sleep and activity monitoring. Inpatient admission is 16 consecutive nights on the Clinical Neuroscience Research Unit and involves subjective and objective tests of sleep, sleepiness, attention, and learning. During inpatient admission subjects will take modafinil or placebo. For follow-up, subjects will return to the CNRU for one night and again participate in objective tests of sleep, sleepiness, attention, and learning. We hypothesize that modafinil will decrease subject and objective measures of sleepiness and will promote attention and learning in cocaine dependent persons.
|
A relatively new treatment for the excessive daytime sleepiness (EDS) associated with inadequate sleep is the drug modafinil. Modafinil decreases subjective reports and objective measures of daytime sleepiness under conditions of sleep restriction, while enhancing cognitive performance. At the same time, sleep quality does not appear to be affected significantly. Interestingly, recent clinical trials in cocaine-dependent populations suggest that modafinil reduces the relapse to cocaine use, by unknown mechanisms.
We propose to employ both subjective and objective measures of nocturnal sleep and daytime sleepiness, as well as measures of general cognitive performance and sleep-dependent memory consolidation, to explore potential mechanistic relationships between cocaine abstinence, EDS, and modafinil's efficacy in preventing cocaine relapse.
The following specific aims are proposed:
Specific Aim 1: To establish whether objective measures of poor nocturnal sleep (e.g., reduced total sleep time and sleep efficiency) that progressively characterize periods of sustained cocaine abstinence are also associated with objective evidence of excessive daytime sleepiness (EDS).
Specific Aim 2: To establish the ability of modafinil to reverse the excessive daytime sleepiness (EDS) and deficits in cognitive performance that characterize cocaine abstinence.
Specific Aim 3: To conduct a pilot study to determine whether the observed abnormalities in objective sleep, EDS, and/or cognitive function predict relapse to cocaine use and/or whether successful abstinence from cocaine is associated with normalization of the same.
|
Cocaine Dependence Substance-induced Sleep Disorder Substance-induced Cognitive Disorder
|
Modafinil Sleep Cognition Cocaine Dependence
| null | 2
|
arm 1: Modafinil 400mg orally everyday for 16 days arm 2: Placebo orally everyday for 16 days
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Modafinil 400mg orally every day for 16 days intervention 2: Placebo orally everyday for 16 days
|
intervention 1: Modafinil intervention 2: Placebo
| 1
|
New Haven | Connecticut | United States | -72.92816 | 41.30815
| 0
|
NCT00582491
|
[
3
] | 40
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| null |
This study is designed to test the safety and feasibility of the simultaneous administration of a biphosphonate with chemotherapy for the treatment of osteosarcoma in newly diagnosed patients.
| null |
Osteosarcoma
|
Cisplatin Doxorubicin Methotrexate Osteosarcoma 03-074
| null | 1
|
arm 1: None
|
[
0
] | 3
|
[
0,
0,
0
] |
intervention 1: Cisplatin 120 mg/m\^2 intervention 2: 75mg/m\^2 intervention 3: Methotrexate 12g/m\^2
|
intervention 1: Cisplatin intervention 2: Doxorubicin intervention 3: Methotrexate
| 1
|
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT00586846
|
[
0
] | 26
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| true
| 0ALL
| false
|
This was a randomized, blinded study of transforaminal epidural injection of clonidine versus a similar injection of corticosteroid for acute lumbosacral radiculopathy. The hypothesis was that clonidine will be as effective as steroid for this condition.
|
Patients with approximately 3 months of low back pain and leg pain due to intervertebral disc herniation were randomized to transforaminal epidural injections of 2% lidocaine and either clonidine (200 or 400 micrograms) or triamcinolone (40 mg) (corticosteroid). Patients received one to three injections administered at about 2 weeks apart. Patients, investigators, and study coordinators were blinded to the treatment. The primary outcome was an 11-point Pain Intensity Numerical Rating Scale at 1 month. The hypothesis was that clonidine will be as effective as steroid for this condition.
|
Lumbar and Other Intervertebral Disc Disorders With Radiculopathy
|
herniated disk radiculopathy clonidine epidural steroid corticosteroid nucleus pulposus transforaminal
| null | 2
|
arm 1: Transforaminal epidural clonidine injection arm 2: Transforaminal epidural steroid injection
|
[
0,
1
] | 3
|
[
0,
0,
0
] |
intervention 1: 200 or 400 micrograms clonidine intervention 2: 40 or 80 milligrams triamcinolone intervention 3: 1 ml 2% lidocaine (20 mg/mL)
|
intervention 1: Clonidine intervention 2: Triamcinolone hexacetonide intervention 3: Lidocaine HCl
| 1
|
Rochester | Minnesota | United States | -92.4699 | 44.02163
| 0
|
NCT00588354
|
[
5
] | 157
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| true
| 1FEMALE
| false
|
This is a multi-center study to evaluate the effects of SCE-B on nocturnal vasomotor symptoms. Study duration will be approximately 16 weeks; this includes a 4-week screening period and approximately 5 scheduled clinic visits. Participants will receive one of two strengths of SCE-B tablets plus matching placebo or placebo only, and will have a physical and gynecological exams that may include transvaginal ultrasound, endometrial biopsy and a pap smear. Participants will be asked to wear a monitoring device for a portion of the study and be asked to complete a daily dairy.
| null |
Nocturnal Vasomotor Symptoms
|
Nocturnal vasomotor symptoms in postmenopausal women
| null | 3
|
arm 1: 0.3 mg SCE-B Daily arm 2: 0.625 mg SCE-B Daily arm 3: Placebo
|
[
0,
0,
2
] | 2
|
[
0,
0
] |
intervention 1: 0.3 mg or 0.625 mg SCE-B tablets daily plus matching placebo intervention 2: Matching placebo for 0.3 mg and 0.625 mg tablets
|
intervention 1: SCE-B intervention 2: Placebo
| 17
|
Anaheim | California | United States | -117.9145 | 33.83529
Sacramento | California | United States | -121.4944 | 38.58157
San Diego | California | United States | -117.16472 | 32.71571
Clearwater | Florida | United States | -82.8001 | 27.96585
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Lexington | Kentucky | United States | -84.47772 | 37.98869
Louisville | Kentucky | United States | -85.75941 | 38.25424
Lincoln | Nebraska | United States | -96.66696 | 40.8
Moorestown | New Jersey | United States | -74.94267 | 39.96706
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Cleveland | Ohio | United States | -81.69541 | 41.4995
Mayfield Heights | Ohio | United States | -81.4579 | 41.51922
Medford | Oregon | United States | -122.87559 | 42.32652
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Columbia | South Carolina | United States | -81.03481 | 34.00071
San Antonio | Texas | United States | -98.49363 | 29.42412
| 0
|
NCT00592839
|
[
3
] | 12
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| false
|
As a consequence of damage to multiple organ systems throughout the course of their disease, diabetic patients suffer a number of chronic complications giving rise to increased morbidity, mortality, and health care costs specific to this population. Within the ophthalmic domain, diabetic retinopathy (DR) frequently induces serious visual impairment. Although DR can be addressed surgically, surgery remains a less than ideal intervention within this population with a well-characterized compromised ability to heal. The introduction of a therapeutic agent that could accelerate wound closure and decrease healing time, thereby reducing the risk and incidence of infection and corneal scarring in these susceptible patients, would represent a significant clinical and pharmacoeconomic advance in the treatment of this condition.
|
In individuals with certain clinical conditions, such as diabetes, corneal epithelial defects persist and do not necessarily respond to conventional treatment regimens because of delayed epithelial wound healing. While wound closure should occur following an injury to the corneal epithelium, a timely re-establishment of the epithelial barrier is of utmost importance.
The wound repair process is intricately linked to a complex inflammatory response that must be properly regulated to ensure healing and optimal visual outcome. Infiltration of inflammatory cells into injured corneal tissue is a hallmark of wound repair, and the association of polymorphonuclear (PMN) leukocyte infiltration with sterile corneal ulceration is well recognized. Retardation of epithelial recovery by persistent inflammation, release of enzymatic products from degranulating PMN, and stimulation of mononuclear leukocytes by cytokines all contribute to poor re-epithelialization.
It has been shown that diabetic corneas manifest reduced rates of epithelial healing after denudement. Yet, in the diabetic patient, not only is the rate of corneal epithelial healing of clinical concern, abnormalities inherent in the diabetic corneal epithelial cytoarchitecture can cause substantial impediments to normal stromal healing. Histologically, diabetic corneas typically demonstrate thickening of the epithelial basal membrane (BM), decreased number of hemidesmosomes, and decreased number of nerve fiber endings. Studies of BM changes in diabetic corneas have yielded information regarding poor adhesion of the epithelial BM to the stroma. During vitrectomy in diabetic patients, when the cornea epithelium is removed, it separates as an intact sheet and the entire thickened BM, characteristic of diabetes, adheres to the epithelium. In contrast, when normal epithelium is removed by scraping, the BM remains adherent to the stroma.
Because patients with diabetic retinopathy (DR) corneas have delayed wound healing, the expression of thymosin beta 4 (Tβ4) as a potent epithelial cell migration stimulator in DR corneas was investigated. Human DR corneas were analyzed and were found to express significantly less Tβ4 compared to normal corneas, suggesting that the use of Tβ4 may accelerate the wound-healing process in this model.
|
Diabetes
|
Thymosin beta 4 Corneal wound healing Vitrectomy Diabetes
| null | 2
|
arm 1: There are 2 groups: active drug and placebo. The patients in the placebo arm receive an administration of eyedrops to the affected eye, identical to the active drug but with no thymosin beta 4 (0.00% thymosin beta 4, w/w), 2 drops 4 times a day (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy). arm 2: There are 2 groups: active drug and placebo. The patients in the active comparator arm receive an administration of 0.01% Tβ4 (w/w) eyedrops to the affected eye, 2 drops 4 times a day (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).
|
[
2,
1
] | 2
|
[
0,
10
] |
intervention 1: There are 2 groups: active drug and placebo. The patients in the active arm receive an administration of 0.01% Tβ4 (w/w) eyedrops to the affected eye, 2 drops 4 times daily (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy). intervention 2: There are 2 groups: active drug and placebo. The patients in the placebo arm receive an administration of 0.00% Tβ4(w/w) eyedrops to the affected eye, 2 drops four times a day (QID) (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).
|
intervention 1: Thymosin Beta 4 (Tβ4) intervention 2: Placebo
| 5
|
Inglewood | California | United States | -118.35313 | 33.96168
Los Angeles | California | United States | -118.24368 | 34.05223
Orlando | Florida | United States | -81.37924 | 28.53834
Augusta | Georgia | United States | -81.97484 | 33.47097
Asheville | North Carolina | United States | -82.55402 | 35.60095
| 0
|
NCT00598871
|
[
3
] | 166
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
This trial will investigate the use of the newer targeted agents erlotinib and sorafenib in patients with stage IIIB or stage IV NSCLC who have received 1-2 prior chemotherapy regimens. Patients will be randomized to receive erlotinib (150 mg/day) and sorafenib (400 mg twice daily), or erlotinib (150 mg/day) and a placebo.
|
The rationale of this study is to combine two distinct kinase inhibitors to evaluate synergistic inhibition of angiogenesis and epidermal growth factor receptor (EGFR) signaling. Erlotinib is a oral tyrosine kinase inhibitor that targets EGFR. Sorafenib is a oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor beta, Raf-1, Flt-3, and C-kit. These agents also do not exhibit overlapping adverse event profiles which provided additional support for studying this combination therapy.
|
Non-Small Cell Lung Cancer
|
Non-Small Cell Lung Cancer Advanced Sorafenib Erlotinib Double-blind Placebo-controlled
| null | 2
|
arm 1: Erlotinib + Sorafenib arm 2: Erlotinib + Placebo
|
[
0,
2
] | 2
|
[
0,
0
] |
intervention 1: Patients who are randomized to Cohort A will take sorafenib 400 mg (2 x 200-mg tablets) orally twice a day, and erlotinib 150 mg orally once a day. intervention 2: Patients who are randomized to Cohort B will take erlotinib 150 mg orally once a day and placebo orally twice a day.
|
intervention 1: Erlotinib + Sorafenib intervention 2: Erlotinib + Placebo
| 16
|
Fort Myers | Florida | United States | -81.84059 | 26.62168
Gainesville | Georgia | United States | -83.82407 | 34.29788
Marietta | Georgia | United States | -84.54993 | 33.9526
Overland Park | Kansas | United States | -94.67079 | 38.98223
Bethesda | Maryland | United States | -77.10026 | 38.98067
Grand Rapids | Michigan | United States | -85.66809 | 42.96336
Omaha | Nebraska | United States | -95.94043 | 41.25626
Asheville | North Carolina | United States | -82.55402 | 35.60095
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Columbus | Ohio | United States | -82.99879 | 39.96118
Columbia | South Carolina | United States | -81.03481 | 34.00071
Chattanooga | Tennessee | United States | -85.30968 | 35.04563
Collierville | Tennessee | United States | -89.66453 | 35.04204
Nashville | Tennessee | United States | -86.78444 | 36.16589
Corpus Christi | Texas | United States | -97.39638 | 27.80058
Richmond | Virginia | United States | -77.46026 | 37.55376
| 0
|
NCT00600015
|
[
3
] | 40
|
RANDOMIZED
|
CROSSOVER
| 7BASIC_SCIENCE
| 2DOUBLE
| true
| 1FEMALE
| false
|
The ultimate aim of this study is to test the hypothesis that the oral cholecystokinin (CCK) agonist GSKI181771X will reduce the size of a binge meal among individuals with Bulimia Nervosa. The study will be conducted in phases. First, an effective dose for reducing food intake, when normal subjects eat normally will be attained. Next, it will be determined whether intake at this dose is reduced in control subjects instructed to eat to capacity. If the dose is still effective compared to placebo, the same dose will be tested in patients with bulimia nervosa.
|
This study tests the hypothesis that an oral CCK antagonist GSKI181771X will reduce the size of a binge meal. It was intended to study the effects of increasing doses on antagonist on normal individuals to find an effective dose in a non-binge meal before moving to a binge meal. Once the effects of the antagonist on a binge meal were found, the compound would be used on patients with bulimia nervosa. However, the product expired and more was not available before the patients were tested. Data are presented for the normal participants who were instructed to eat normally, followed by a group that was instructed to binge eat. Comparisons were made between groups with different instructions and between binge and normal meals.
|
Bulimia
|
Eating Food Intake Appetite
| null | 8
|
arm 1: 'Instructions to eat normally' Placebo 1 mg dose arm 2: 'Instructions to eat normally' drug 1 mg dose 'GSKI181771X (CCK-1R agonist)' arm 3: 'Instructions to eat normally' 2 mg placebo arm 4: 'Instructions to eat normally' 2 mg drug 'GSKI181771X (CCK-1R agonist)' arm 5: 'Instructions to eat normally' 4 mg placebo arm 6: 'Instructions to eat normally' 4 mg drug 'GSKI181771X (CCK-1R agonist)' arm 7: Instructions to binge eat 4 mg placebo arm 8: Instructions to binge eat 4 mg drug 'GSKI181771X (CCK-1R agonist)'
|
[
2,
1,
2,
1,
2,
1,
2,
1
] | 4
|
[
0,
5,
5,
0
] |
intervention 1: Drug one trial vs placebo intervention 2: Subjects will be instructed to binge eat and will also be given either drug or placebo intervention 3: Subjects will be instructed to eat normally and will also be given either drug or placebo intervention 4: Drug one trial vs placebo
|
intervention 1: GSKI181771X (CCK-1R agonist) intervention 2: Instructions to binge eat intervention 3: Instructions to eat normally intervention 4: Placebo
| 1
|
New York | New York | United States | -74.00597 | 40.71427
| 0
|
NCT00600743
|
[
4
] | 4
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this clinical research study is to find out whether a combination of entecavir (ETV) plus tenofovir (TNF) works better against Hepatitis B virus than adefovir (ADV) added to continuing lamivudine (LVD) therapy in patients whose Hepatitis B virus (HBV) is resistant against lamivudine. The safety of this treatment will also be studied.
| null |
Chronic Hepatitis B
| null | 2
|
arm 1: None arm 2: None
|
[
0,
0
] | 2
|
[
0,
0
] |
intervention 1: Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks intervention 2: Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
|
intervention 1: Entecavir + Tenofovir intervention 2: Adefovir + continuing Lamivudine
| 29
|
Los Angeles | California | United States | -118.24368 | 34.05223
San Francisco | California | United States | -122.41942 | 37.77493
Chicago | Illinois | United States | -87.65005 | 41.85003
New York | New York | United States | -74.00597 | 40.71427
Brussels | N/A | Belgium | 4.34878 | 50.85045
Leuven | N/A | Belgium | 4.70093 | 50.87959
Berlin | N/A | Germany | 13.41053 | 52.52437
Bonn | N/A | Germany | 7.09549 | 50.73438
Düsseldorf | N/A | Germany | 6.77616 | 51.22172
Mainz | N/A | Germany | 8.2791 | 49.98419
Messina | N/A | Italy | 15.55256 | 38.19394
Modena | N/A | Italy | 10.92539 | 44.64783
Naples | N/A | Italy | 14.26811 | 40.85216
Padua | N/A | Italy | 11.88586 | 45.40797
San Giovanni Rotondo | N/A | Italy | 15.7277 | 41.70643
Chorzów | N/A | Poland | 18.9742 | 50.30582
Krakow | N/A | Poland | 19.93658 | 50.06143
Lublin | N/A | Poland | 22.56667 | 51.25
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Kocaeli | N/A | Turkey (Türkiye) | 27.51145 | 39.62497
Sihhiye Ankara | N/A | Turkey (Türkiye) | N/A | N/A
Trabzon | N/A | Turkey (Türkiye) | 39.72694 | 41.005
| 0
|
NCT00605384
|
|
[
0
] | 34
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| true
|
To evaluate galantamine's effects on cognitive performance in abstinent cocaine users. Galantamine, a medication approved for treatment of Alzheimer's disease, is an acetylcholine esterase inhibitor. Galantamine also directly potentiates nicotine receptors. Both of these effects may result in improved cognitive performance in a group of subjects known to have impaired performance in various cognitive tasks.
|
Galantamine, compared to placebo, will improve cognitive performance in abstinent cocaine users. The cognitive performance will be measured with the Stroop test and 3 Cambridge Neuropsychological Test Automated Battery (CANTAB) tests: Paired Associate Learning (PAL), Delayed Pattern Recognition Memory (PRM),and Rapid Visual Information Processing (RVIP). Performance on these tests has been shown to be impaired in abstinent cocaine users, compared to healthy controls.
Galantamine, compared to placebo, will not be associated with any significant changes in mood. Monitoring of mood will be achieved with 3 mood scales: 1) Center for Epidemiologic Studies Depression (CES-D) scale, Positive and Negative Affect Schedule (PANAS) and the Profile of Mood States (POMS).
Currently this study is completed, Patients are no longer being enrolled. There were 28 completers. This study has been published.
|
Cocaine Abuse
|
cognitive enhancers Nootropic Agents
| null | 2
|
arm 1: Galantamine 8 mg/day arm 2: placebo
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: Galantamine 8 mg/day intervention 2: sugar pill
|
intervention 1: Galantamine intervention 2: placebo
| 1
|
West Haven | Connecticut | United States | -72.94705 | 41.27065
| 0
|
NCT00606801
|
[
5
] | 6
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this study is to determine if calcipotriene/bethamethasone can safely and effectively manage the occurence of LMB (mild localized breakthrough) in patients recieving efalizumab (Raptiva) for moderate to severe plaque psoriasis.
It is hypothesized that calcipotriene/betamethasone (Taclonex) could be used to manage LMB and thus allow patients to continue efalizumab without interruption.
|
LMB (localized mild breakthrough)is one of two psoriasis adverse events commonly seen in efalizumab treated patients. It is generally papular in nature and does not involve existing lesions. Clinical experience suggests that LMB may not have a clinical impact in patients responding to efalizumab and therefore may be treated without interrupting efalizumab therapy. To relieve discomfort topical therapy may be indicated until the symptoms are resolved.
This is a single arm, open label study. Fifteen patients who are receiving efalizumab before entrance into this study and who develop LMB wil be enrolled. Topical calcipotriene/betamethasone (Taclonex) will be applied to the areas (except face, axillae or groin) once a day for two weeks. The PI may choose to continue two more weeks if needed for a total of four weeks of therapy. All patients will continue with efalizumab without dose modification for the duration of the study. Patients will return for follow up visits at weeks 2, 4 and 6. Topical desonide may be used for LMB involvement of the face, groin or axillae.
|
Plaque Psoriasis
|
Localized mild breakthrough
| null | 0
| null | null | 1
|
[
0
] |
intervention 1: One application to affected areas, once a day for two weeks. The PI may choose to extend treatment until Week 4 if necessary.
|
intervention 1: Calcipotriene/betamethasone
| 1
|
Louisville | Kentucky | United States | -85.75941 | 38.25424
| 0
|
NCT00608777
|
[
4
] | 929
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| false
|
This trial is conducted in Asia. The trial is designed to compare the effect on glycaemic control of liraglutide or glimepiride added to metformin in subjects with type 2 diabetes
| null |
Diabetes Diabetes Mellitus, Type 2
| null | 4
|
arm 1: Liraglutide 0.6 mg + metformin + glimepiride placebo arm 2: Liraglutide 1.2 mg + metformin + glimepiride placebo arm 3: Liraglutide + metformin + glimepiride placebo arm 4: Glimepiride 4.0 mg + metformin + liraglutide placebo
|
[
0,
0,
0,
0
] | 7
|
[
0,
0,
0,
0,
0,
0,
0
] |
intervention 1: 0.6 mg/day, s.c. (under the skin) injection intervention 2: Glimepiride placebo, capsules intervention 3: 1.2 mg/day, s.c. (under the skin) injection intervention 4: 1.8 mg/day, s.c. (under the skin) injection intervention 5: Capsules, 4.0 mg/day intervention 6: Tablets, 1.5-2.0 g/day intervention 7: Liraglutide placebo, s.c. (under the skin) injection
|
intervention 1: liraglutide intervention 2: placebo intervention 3: liraglutide intervention 4: liraglutide intervention 5: glimepiride intervention 6: metformin intervention 7: placebo
| 50
|
Beijing | Beijing Municipality | China | 116.39723 | 39.9075
Beijing | Beijing Municipality | China | 116.39723 | 39.9075
Chongqing | Chongqing Municipality | China | 106.55771 | 29.56026
Fuzhou | Fujian | China | 119.30611 | 26.06139
Harbin | Heilongjiang | China | 126.65 | 45.75
Harbin | Heilongjiang | China | 126.65 | 45.75
Wuhan | Hubei | China | 114.26667 | 30.58333
Nanjing | Jiangsu | China | 118.77778 | 32.06167
Suzhou | Jiangsu | China | 120.59538 | 31.30408
Wuxi | Jiangsu | China | 120.28857 | 31.56887
Xi'an | Shaanxi | China | 108.92861 | 34.25833
Shanghai | Shanghai Municipality | China | 121.45806 | 31.22222
Hangzhou | Zhejiang | China | 120.16142 | 30.29365
Shenyang | N/A | China | 123.43278 | 41.79222
Tianjin | N/A | China | 117.17667 | 39.14222
Wuhan | N/A | China | 114.26667 | 30.58333
Hyderabad | Andhra Pradesh | India | N/A | N/A
Hyderbad | Andhra Pradesh | India | N/A | N/A
Ahmedabad | Gujarat | India | 72.58727 | 23.02579
Bangalore | Karnataka | India | 77.59369 | 12.97194
Kochi | Kerala | India | 76.26022 | 9.93988
Mumbai | Maharashtra | India | 72.88261 | 19.07283
Pune | Maharashtra | India | 73.85535 | 18.51957
New Dehli | New Delhi | India | N/A | N/A
Bhubaneswar | Odisha | India | 85.83385 | 20.27241
Jaipur | Rajasthan | India | 75.78781 | 26.91962
Chennai | Tamil Nadu | India | 80.27847 | 13.08784
Madurai | Tamil Nadu | India | 78.11953 | 9.919
Kolkata | West Bengal | India | 88.36304 | 22.56263
Ghaziabad | N/A | India | 77.43915 | 28.66535
Kochi | N/A | India | 76.26022 | 9.93988
Kolkata | N/A | India | 88.36304 | 22.56263
Kolkata | N/A | India | 88.36304 | 22.56263
Mumbai | N/A | India | 72.88261 | 19.07283
Mumbai | N/A | India | 72.88261 | 19.07283
New Delhi | N/A | India | 77.2148 | 28.62137
Patna | N/A | India | 85.13563 | 25.59408
Secunderabad | N/A | India | 78.54263 | 17.50427
Trivandrum | N/A | India | 76.94924 | 8.4855
Visakhapatnam | N/A | India | 83.20161 | 17.68009
Goyang | N/A | South Korea | 127.19731 | 36.21689
Incheon | N/A | South Korea | 126.70515 | 37.45646
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Sungnam | N/A | South Korea | N/A | N/A
Suwon | N/A | South Korea | 127.00889 | 37.29111
| 0
|
NCT00614120
|
|
[
5
] | 6
|
NON_RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
This study will test the effectiveness and the safety of giving two antifungal agents (voriconazole and anidulafungin) together to treat invasive aspergillosis in patients who are unable to tolerate polyene therapy.
|
The study was terminated on January 12, 2009 due to the overall low rate of enrollment. The decision to terminate the trial was not based on any safety concerns. Patients who were enrolled in the study prior to January 12, 2009 were allowed to remain in the study until completing their participation as specified in the protocol.
|
Aspergillosis
|
invasive aspergillosis, opportunistic mold infection
| null | 2
|
arm 1: anidulafungin plus voriconazole arm 2: anidulafungin plus voriconazole
|
[
0,
0
] | 2
|
[
0,
0
] |
intervention 1: Subjects with creatinine clearance at least 50 ml/min will receive initial treatment with IV (loading dose of 6 mg/kg Q12h followed by maintenance dose of 4 mg/kg Q12h) or oral (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Subjects with creatinine clearance \<50 ml/min will receive oral voriconazole (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). intervention 2: Loading dose of 200 mg QD followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy
|
intervention 1: voriconazole intervention 2: anidulafungin
| 4
|
Atlanta | Georgia | United States | -84.38798 | 33.749
Detroit | Michigan | United States | -83.04575 | 42.33143
Fort Worth | Texas | United States | -97.32085 | 32.72541
Fort Worth | Texas | United States | -97.32085 | 32.72541
| 0
|
NCT00620074
|
[
4
] | 108
|
RANDOMIZED
|
PARALLEL
| 1PREVENTION
| 4QUADRUPLE
| true
| 1FEMALE
| false
|
The primary purpose of this study is to demonstrate the bioequivalence of IMPLANON and Radiopaque IMPLANON.
| null |
Contraception
| null | 2
|
arm 1: The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate. arm 2: Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and
2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after
insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
[
1,
1
] | 2
|
[
0,
0
] |
intervention 1: Radiopaque rod for 3 years intervention 2: Implanon (etonogestrel implant) for 3 years
|
intervention 1: Radiopaque Implanon intervention 2: Implanon (etonogestrel implant)
| 0
| null | 0
|
NCT00620464
|
|
[
0
] | 87
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| true
|
Cardiopulmonary bypass \[CPB\] in small size bodies can result in decreased peripheral perfusion. This results in anaerobic metabolism as evidenced by lactic acidosis. High flow perfusion results in systemic hypertension which is accentuated by moderate hypothermia commonly used during cardiopulmonary bypass. Phenoxybenzamine \[PBZ\] is an arteriolar vasodilator that acts by irreversibly blocking the alpha adrenergic receptors. It causes vasodilatation allowing high flow, low pressure CPB. It has been used extensively outside US in Canada, Europe and Australia. In the US oral PBZ is FDA approved, whereas intravenous PBZ is only available as an investigational drug
|
Background Cardiopulmonary bypass \[CPB\] in small size bodies can result in decreased peripheral perfusion. This results in anaerobic metabolism as evidenced by lactic acidosis. High flow results in systemic hypertension which is accentuated by moderate hypothermia commonly used during cardiopulmonary bypass. Phenoxybenzamine \[PBZ\] is an arteriolar vasodilator that acts by irreversibly blocking the alpha adrenergic receptors. It causes vasodilatation allowing high flow, low pressure CPB. It has been used extensively outside US in Canada, Europe and Australia. In the US oral PBZ is FDA approved, whereas intravenous PBZ is only available as an investigational drug. At the Cleveland Clinic this medication has been used under this protocol since 1994 in \>1000 without any significant or serious adverse outcome. The drug is also used at Texas Children's Hospital, Hospital for Sick Children in Toronto, Children's Hospital of Wisconsin and a number of centers throughout Europe, Australia and Asia. The drug has helped reduce the mortality of children undergoing cardiopulmonary bypass.
The theoretic benefit of PBZ in this patient population is uniform and smooth reduction fo systemic vascular resistance in the perioperative period. This uniform systemic vasodilation allows low pressure, high flow systemic perfusion on cardiopulmonary bypass. We feel that this ins in part responsible for improved outcome after cardiopulmonary bypass, including less end-organ edema formation and dysfunction. Due to experience in this and other centers we strongly believe that the use of PBZ in the bypass management protocol of these patients represents the state-of-the-art and not an experimental investigation. Since in the US the drug is not available except as an investigational drug, we have been required to use it as an investigational new drug \[IND\] PBZ\[oral\] is currently used in the US for the management of pheochromocytoma. It has a proven track record and known to be safe. Use in a large number of patients worldwide has shown no serious side-effects except hypotension \[which is an effect indeed\] requiring norepinephrine \[an alpha agonist commonly used after cardiopulmonary bypass in these patients anyway\].
Patients
The following patients are candidates for receiving PBZ for HFLPP. These include:
1. All patients under 16 kg.
2. Those patients between 16-18 kg whose pre bypass hemoglobin is \<16 g/dl
3. All patients are less than 18 years of age.
Use of Phenoxybenzamine:
Loading dose given at the time of going on CPB:
* For patients with obstructing lesions on systemic side:
* 0.25 mg/kg dose in the bypass circuit
* None intravenous
* For patients without obstructing left sided lesions:
* 0.5 mg/kg in the bypass circuit
* 0.5 mg/kg I.V. at cannulation
Maintenance dose given in the post-operative period:
* 0.3 mg/kg I.V. every 8 hours till oral intake is started or for first 48 hours
* 0.3 mg/kg P.O. every 8 hours for next 24 hours
* 0.15 mg/kg P.O. every 8 hours for next 24 hours and then stop
* Hold PBZ if the patient is on norepinephrine infusion or the mean arterial pressure is lower than that allowed for the age group
* Do not use maintenance dose in the following patients unless they are on maximum dose of sodium nitroprusside infusion and still hypertensive:
* Norwood patients
* Fontan patients
* Patients with residual left ventricular obstructive lesions - don't use at all in the post operative period
Data collected and monitored for the purpose of this study only:
Demographic information, side effects and mortality data would be recorded and kept in a password protected computer in a secure-access-only physician office. Only composite data without individual identifiers will be reported to the IRB and FDA. No publication is planned from this study and no follow-up will be done after the patient is discharged from the hospital.
Side effects to be monitored:
* Hypotension requiring norepinephrine in excess of usual dose \[0.2 micrograms/kg/min\]
* Death from such hypotension in the absence of other causes \[such as bleeding, sepsis\]
* Effects occuring within 12 hours of I.V. dose administration or within 24 hours of P.O. dose administration
* Any unanticipated or unusual side effects \[none noted since 1994\] Consent Informed consent would be obtained from the parents/guardians of all patients. Assent will be obtained from children of \>7 years age.
|
Congenital Heart Surgery Cardiopulmonary Bypass
|
Congenital heart surgery Cardiopulmonary bypass Phenoxybenzamine
| null | 1
|
arm 1: Treatment Group
|
[
0
] | 1
|
[
0
] |
intervention 1: Use of Phenoxybenzamine:
Loading dose given at the time of going on CPB:
* For patients with obstructing lesions on systemic side:
* 0.25 mg/kg dose in the bypass circuit
* None intravenous
* For patients without obstructing left sided lesions:
* 0.5 mg/kg in the bypass circuit
* 0.5 mg/kg I.V. at cannulation
Maintenance dose given in the post-operative period:
* 0.3 mg/kg I.V. every 8 hours till oral intake is started or for first 48 hours
* 0.3 mg/kg P.O. every 8 hours for next 24 hours
* 0.15 mg/kg P.O. every 8 hours for next 24 hours and then stop
* Hold PBZ if the patient is on norepinephrine infusion or the mean arterial pressure is lower than that allowed for the age group
|
intervention 1: Phenoxybenzamine
| 0
| null | 0
|
NCT00620945
|
[
3
] | 15
|
NA
|
SINGLE_GROUP
| 0TREATMENT
| 0NONE
| false
| 0ALL
| false
|
The purpose of this study is to assess the efficacy and safety after administration of MP-424 to patients with chronic hepatitis C.
| null |
Hepatitis C
|
Chronic Hepatitis C Protease Inhibitor
| null | 1
|
arm 1: None
|
[
0
] | 1
|
[
0
] |
intervention 1: Three tablets of MP-424 250mg tablet at a time, every 8 hours, 24 weeks administration (dose in a day: 2250 mg)
|
intervention 1: MP-424 (Telaprevir)
| 1
|
Kawasaki | Takatsu-ku | Japan | 139.71722 | 35.52056
| 0
|
NCT00621296
|
[
3
] | 45
|
RANDOMIZED
|
CROSSOVER
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| null |
This study will assess the safety, tolerability, and pharmacodynamics of CK-1827452 infusion in patients with stable heart failure.
| null |
Heart Failure
| null | 5
|
arm 1: 4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. arm 2: 4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. arm 3: 4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. arm 4: 4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. arm 5: 2 treatment periods with a 72 hour infusion. The 2 treatment periods are randomly assigned and consist of 1 dose level of CK-1827452 (with dose de-escalation possible depending on tolerability) and 1 placebo treatment. Treatment period 2 occurs at least 7 days after the conclusion of period 1.
|
[
0,
0,
0,
0,
0
] | 16
|
[
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
intervention 1: IV infusion for 1 hour at 0.125 mg/kg/h followed by 1 hour at 0.0625 mg/kg/h intervention 2: IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h intervention 3: IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h intervention 4: IV infusion for 1 hour at 0.75 mg/kg/h followed by 1 hour at 0.375 mg/kg/h intervention 5: IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h intervention 6: IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h followed by 22 hours at 0.025 mg/kg/h intervention 7: IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h followed by 22 hours at 0.05 mg/kg/h intervention 8: IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h followed by 22 hours at 0.1 mg/kg/h intervention 9: IV infusion for 2 hours intervention 10: IV infusion for 24 hours intervention 11: IV infusion for 1 hour at 1.0 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h intervention 12: IV infusion for 72 hours intervention 13: IV infusion for 1 hour at 0.75 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h intervention 14: IV infusion for 1 hour at 0.25 mg/kg/h followed by 23 hours at 0.025 mg/kg/h intervention 15: IV infusion for 1 hour at 0.5 mg/kg/h followed by 23 hours at 0.05 mg/kg/h intervention 16: IV infusion for 1 hour at 1.0 mg/kg/h followed by 23 hours at 0.1 mg/kg/h
|
intervention 1: CK-1827452 intervention 2: CK-1827452 intervention 3: CK-1827452 intervention 4: CK-1827452 intervention 5: CK-1827452 intervention 6: CK-1827452 intervention 7: CK-1827452 intervention 8: CK-1827452 intervention 9: Placebo intervention 10: Placebo intervention 11: CK-1827452 intervention 12: Placebo intervention 13: CK-1827452 intervention 14: CK-1827452 intervention 15: CK-1827452 intervention 16: CK-1827452
| 17
|
San Diego | California | United States | -117.16472 | 32.71571
Newark | Delaware | United States | -75.74966 | 39.68372
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Hull | England | United Kingdom | -0.33525 | 53.7446
London | England | United Kingdom | -0.12574 | 51.50853
London | England | United Kingdom | -0.12574 | 51.50853
London | England | United Kingdom | -0.12574 | 51.50853
Manchester | England | United Kingdom | -2.23743 | 53.48095
Manchester | England | United Kingdom | -2.23743 | 53.48095
Manchester | England | United Kingdom | -2.23743 | 53.48095
Middlesex | England | United Kingdom | -0.26856 | 51.53174
Dundee | Scotland | United Kingdom | -2.97489 | 56.46913
Glasgow | Scotland | United Kingdom | -4.25763 | 55.86515
| 0
|
NCT00624442
|
|
[
5
] | 3
|
RANDOMIZED
|
SINGLE_GROUP
| 0TREATMENT
| 4QUADRUPLE
| false
| 0ALL
| true
|
This is a prospective, randomized, double-blinded, placebo controlled pilot safety study that will enroll a total of twenty subjects. Subjects will be adults (30-75) who have sustained a SAH secondary to cerebral aneurysm rupture and who present with minimal neurological symptoms. All subjects will have a Hemoglobin less than or equal to 12 g/dL within 24 hours prior to study entry and undergo operative aneurismal clipping. Subjects will be randomized into two groups, ten subjects receiving the drug and ten subjects receiving the placebo. The subjects will receive three intravenous injections of study drug or placebo, once before undergoing operative aneurysmal clipping (study Day 1) and again for two additional days (study Day 2 and study Day 3).
There are 3 phases to this trial:
Screening Phase - patients will present with Subarachnoid hemorrhage (SAH) and prepped for surgery within 36 hours Treatment Phase - first pre-operative dose before surgery (Study Day 1), post-operative (Study Days 2 and 3) Follow-up Phase- Study Day 4 through discharge, 6-7 week follow-up Primary Objective: To determine the safety of administering intravenous doses of Procrit® once daily for three consecutive days to patients with aneurysmal SAH before and after vascular clipping by comparing the incidence of thrombotic events, hemoglobin and 6-7 week mortality between the Procrit® and placebo groups. Secondary Objectives: To determine if administration of Procrit® prior to aneurysm clipping reduces the incidence of vasospasm following a SAH event treated by vascular clipping. To determine if Procrit® administration prior to aneurysm clipping in patients with Aneurysmal SAH will improve neurological assessment scores in the post-SAH/post-clipping time period. To determine the feasibility of organizing a larger, randomized study to explore the neuroprotective effect of Procrit® in patients with Aneurysmal SubArachnoid Hemorrhage (SAH) when Procrit® is administered prior to surgical clipping of the aneurysm.
It is hypothesized that Procrit will provide a significant level of neuroprotection in the brain after an SAH event as a result of reduced cell death, as well as a reduced amount of vasospasm activity and delayed cerebral ischemia which can occur as a result of SAH. These factors may contribute to improved neurological functioning scores when compared to the placebo treated patients.
| null |
Subarachnoid Hemorrhage
|
Epoetin alfa aneurysm subarachnoid hemorrhage
| null | 2
|
arm 1: Group A will receive Procrit® intravenous injections (40,000U) once daily for 3 days (Study Days 1, 2, and 3). The first dose of Procrit® will be given within 36 hours of the initial SAH event / symptoms and immediately before the vascular clipping procedure. arm 2: Group B will receive Saline intravenous injections once daily for 3 days (Study Days 1, 2, and 3).
|
[
1,
2
] | 2
|
[
0,
0
] |
intervention 1: Intravenous administration of epoetin alfa (40,000 IU) immediately before clipping surgery. Successive doses will be given 24 and 48 hours after the first dose. intervention 2: 3ml of saline will be administered via an IV push immediately before clipping surgery. Successive doses will be given 24 and 48 hours after the first dose.
|
intervention 1: Epoetin alfa intervention 2: Saline
| 1
|
Tampa | Florida | United States | -82.45843 | 27.94752
| 0
|
NCT00626574
|
[
5
] | 97
|
NON_RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 0NONE
| true
| 0ALL
| false
|
The primary purpose of this study is to quantify the change in expression of biomarkers on the ocular surface of Sjogren's Syndrome participants after treatment with Maxidex.
| null |
Sjogren's Syndrome
|
Ocular inflammation
| null | 2
|
arm 1: Maxidex arm 2: Healthy normal control group receiving no treatment
|
[
0,
3
] | 2
|
[
0,
10
] |
intervention 1: Maxidex (0.1% Dexamethasone) 1 drop in each eye 2 times daily intervention 2: Healthy normal control group receiving no treatment
|
intervention 1: Maxidex intervention 2: No treatment
| 2
|
Toronto | N/A | Canada | -79.39864 | 43.70643
Waterloo | N/A | Canada | -80.51639 | 43.4668
| 0
|
NCT00631358
|
[
3
] | 37
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| true
|
4-Week Safety Study in Subjects with Neutrophilic Asthma
|
Effect of treatment with navarixin (MK-7123, SCH 527123) on sputum neutrophils and asthma symptoms
|
Neutrophilic Asthma
| null | 2
|
arm 1: Navarixin (MK-7123, SCH 527123) 30 mg capsule, to be taken by mouth once daily in the morning for 4 weeks arm 2: Placebo capsule to match navarixin, to be taken by mouth once daily in the morning for 4 weeks
|
[
0,
2
] | 3
|
[
0,
0,
0
] |
intervention 1: Navarixin 30 mg capsule to be taken by mouth once daily in the morning for 4 weeks. intervention 2: Placebo capsule to match navarixin to be taken by mouth once daily in the morning for 4 weeks. intervention 3: Participant choice of short-acting beta-2 agonist (salbutamol/albuterol), anticholinergic, or combination medication as needed for asthma symptoms
|
intervention 1: Navarixin intervention 2: Placebo intervention 3: Rescue medication
| 0
| null | 0
|
NCT00632502
|
|
[
2
] | 9
|
NA
|
SINGLE_GROUP
| 9OTHER
| 0NONE
| false
| 0ALL
| false
|
The purpose of this study is to determine the pharmacokinetics of ceftaroline in pediatric subjects
|
The purpose of this study is to determine the pharmacokinetics profile of ceftaroline in pediatric subjects
|
Infection
|
PK Pharmacokinetics
| null | 1
|
arm 1: ceftaroline
|
[
0
] | 1
|
[
0
] |
intervention 1: Single parenteral infusion at a dose of 8 mg/kg for subjects weighing less than 75 kg or at a dose of 600 mg for subjects weighing greater than or equal to 75 kg infused over 60 minutes.
|
intervention 1: ceftaroline
| 4
|
Louisville | Kentucky | United States | -85.75941 | 38.25424
Durham | North Carolina | United States | -78.89862 | 35.99403
Akron | Ohio | United States | -81.51901 | 41.08144
Cleveland | Ohio | United States | -81.69541 | 41.4995
| 0
|
NCT00633126
|
[
5
] | 247
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 2DOUBLE
| false
| 0ALL
| null |
The purpose of this study is to evaluate the efficacy and safety of the FSC HFA MDI in subjects with COPD. The dose of FSC HFA MDI to be evaluated corresponds to the dose of FSC DISKUS (250/50mcg twice-daily) that is indicated for the treatment of COPD associated with chronic bronchitis in the US. This study will last up to approximately 15 weeks, and subjects will visit the clinic 5 times. Subjects will be given breathing tests and will record their peak expiratory flow measurements daily on diary cards. All study related medicines and medical examinations will be provided at no cost. The FSC HFA MDI used in this study has been approved by FDA for use in asthma while the FSC 250/50mcg DISKUS has been approved for use in asthma and COPD.
| null |
Pulmonary Disease, Chronic Obstructive
|
DISKUS Salmeterol Fluticasone Propionate Chronic Obstructive Pulmonary Disease (COPD) Hydroflouroalkane COPD HFA MDI
| null | 2
|
arm 1: None arm 2: None
|
[
1,
0
] | 2
|
[
0,
0
] |
intervention 1: treatment drug intervention 2: treatment drug
|
intervention 1: Fluticasone Propionate/Salmeterol DISKUS 250/50mcg intervention 2: Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a MDI 230/42mcg
| 16
|
Jasper | Alabama | United States | -87.27751 | 33.83122
Mobile | Alabama | United States | -88.04305 | 30.69436
Lafayette | Louisiana | United States | -92.01984 | 30.22409
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Sunset | Louisiana | United States | -92.06845 | 30.41131
Saint Charles | Missouri | United States | -90.48123 | 38.78394
Elizabeth City | North Carolina | United States | -76.25105 | 36.2946
Erie | Pennsylvania | United States | -80.08506 | 42.12922
Charleston | South Carolina | United States | -79.93275 | 32.77632
Gaffney | South Carolina | United States | -81.64982 | 35.07179
Greenville | South Carolina | United States | -82.39401 | 34.85262
Spartanburg | South Carolina | United States | -81.93205 | 34.94957
Union | South Carolina | United States | -81.62371 | 34.71541
Corsicana | Texas | United States | -96.46887 | 32.09543
Richmond | Virginia | United States | -77.46026 | 37.55376
Morgantown | West Virginia | United States | -79.9559 | 39.62953
| 0
|
NCT00633217
|
[
3,
4
] | 124
|
RANDOMIZED
|
PARALLEL
| 0TREATMENT
| 3TRIPLE
| false
| 0ALL
| false
|
This trial has been designed to evaluate the efficacy of specific immunotherapy with SLITone Dermatophagoides mix compared with placebo in subjects with house dust mite allergic asthma, based on asthma medication use during a period of 2 months with a high environmental exposure to mites (autumn 2008).
|
This trial was conducted as a multi-centre, randomised, double-blind, parallel-group, placebo-controlled phase III trial, assessing the efficacy of SLITone Dermatophagoides mix in adults (18-65 years). 5 centres in Spain participated.
Subjects with house dust mite allergic asthma were randomised to receive either SLITone Dermatophagoides mix (active) or placebo treatment (1:1) for approximately 1 year. The trial duration was extended to 2 years. Administration was done sublingually (under the tongue) once daily preferably in the morning. A monodose container comprised the daily dose of 200 STU.
Subjects were kept in asthma control during the entire trial (2 years). Except for during 2 evaluation periods of 2 months in autumn 2007 and autumn 2008, subjects used the medications prescribed by their physician. During the 2 evaluation periods of 2 months in autumn 2007 and autumn 2008, subjects used provided and standardised rhinoconjunctivitis and asthma medications. The asthma medication use was to reflect the subject's asthma status. This was done by treatment with a low maintenance dose of control medication supplemented with rescue medication as needed.
Rhinoconjunctivitis medication during the 2 evaluation periods in autumn 2007 and autumn 2008; to standardise the medication used to relieve rhinoconjunctivitis symptoms, subjects were provided with the following free medications as needed:
* Desloratadine tablet (5 mg per tablet; anti-histamine; Aerus®)
* Budesonide nasal spray (64 µg per puff; inhaled corticosteroid)
* Prednisone tablet (5 mg per tablet; oral corticosteroid)
Subjects were instructed to use this medication instead of their usual medication during the 2 evaluation periods in autumn 2007 and autumn 2008, and to record the used medication and symptoms in the daily diary.
Asthma medication during the evaluation period in autumn 2007; prior to the 2 months evaluation period in autumn 2007, the asthma control medication use was interrupted to obtain a medication-free period. Subjects were provided with the following free medications to standardise the treatment used to relieve asthma symptoms:
* Salbutamol inhaler (200 µg per puff; a short acting β2-agonist; Ventilastin®).
* Budesonide/formoterol inhaler (80/4.5 µg per inhalation; a combination of inhaled corticosteroids and long acting β2-agonist; Symbicort®).
* Prednisone tablet (5 mg per tablet; oral corticosteroid).
Subjects were instructed to use this medication instead of their usual medication during the evaluation period in autumn 2007 as follows:
They were to use salbutamol inhaler as asthma rescue medication until they either:
* needed more than 4 inhalations of salbutamol per day for 2 consecutive days
* suffered from nocturnal asthma forcing them to wake up
* suffered from exercise-induced dyspnoea doing ordinary tasks In these cases, subjects were to contact the investigator to determine the amount of budesonide/formoterol to use as daily asthma control medication. The budesonide/formoterol inhaler was thereafter to be used as rescue medication as needed instead of salbutamol. Prednisone could be used as a last option.
Asthma medication during the evaluation period in autumn 2008: At the 2 months evaluation period in autumn 2008, subjects were maintained at a low dose of budesonide/formoterol (daily asthma control medication) and they used the budesonide/formoterol inhaler as rescue medication as needed. Prednisone could be used as a last option.
Asthma medication used during the evaluation periods in autumn 2007 and autumn 2008 were recorded in a daily diary.
One primary efficacy endpoint and 16 secondary efficacy endpoints were assessed; the result of the primary efficacy endpoint, 3 secondary endpoints and adverse event reportings are posted here. None of the other secondary endpoints demonstrated a difference between treatment groups.
|
Allergy
|
House dust mites Sublingual immunotherapy Allergy Allergic asthma
| null | 2
|
arm 1: SLITone Dermatophagoides Mix arm 2: SLITone Placebo
|
[
1,
2
] | 7
|
[
2,
2,
0,
0,
0,
0,
0
] |
intervention 1: Sublingual immunotherapy with SLITone Dermatophagoides mix (200 STU) once daily for 2 years intervention 2: Sublingual immunotherapy once daily for 2 years intervention 3: 200 µg per puff; a short acting beta2-agonist (please refer to the 'detailed description' for details on the use) intervention 4: 80/4.5 µg per inhalation; a combination of inhaled corticosteroids and long acting beta2-agonist (please refer to the 'detailed description' for details on the use) intervention 5: 5 mg per tablet; oral corticosteroids (please refer to the 'detailed description' for details on the use) intervention 6: 5 mg per tablet: anti-histamine (please refer to the 'detailed description' for details on the use) intervention 7: 64 µg per puff; inhaled corticosteroid (please refer to the 'detailed description' for details on the use)
|
intervention 1: SLITone(TM) Dermatophagoides mix intervention 2: Placebo intervention 3: Salbutamol inhaler intervention 4: Budesonide/formoterol inhaler intervention 5: Prednisone tablet intervention 6: Desloratadine tablet intervention 7: Budesonide nasal spray
| 1
|
Santander | Cantabria | Spain | -3.80444 | 43.46472
| 0
|
NCT00633919
|
[
5
] | 6
|
RANDOMIZED
|
PARALLEL
| 9OTHER
| 3TRIPLE
| true
| 0ALL
| false
|
This study examines the effects of an antidepressant medication and placebo on the brain functioning of normal subjects. In this study, recordings of brain electrical activity are being used to detect and monitor the response to treatment with venlafaxine IR (Effexor), a drug used for the treatment of depression. The intent of this study is to test specific hypotheses regarding:
1. long-term brain effects of a single course of antidepressant treatment
2. pharmaco-conditioning effects underlying antidepressant tolerance/sensitization
3. brain functional response to initial versus subsequent antidepressant trials in normal healthy subjects.
|
Major Depressive Disorder (MDD) is a lifelong and recurrent illness, such that many individuals require multiple courses of antidepressant medication treatment. While some patients respond completely to each course of treatment, many do not, and with each unsuccessful antidepressant trial the likelihood that a patient will respond decreases. This raises the possibility that neurophysiologic response in subsequent antidepressant treatment may be influenced by learning processes including sensitization, habituation, and/or classical conditioning. Classical conditioning would entail the association of cues such as pill-taking (conditioned stimuli; CS) with the effects of active medication (unconditioned stimulus; US), such that later presentation of the CS alone would come to elicit a conditioned response (CR). Such effects could be revealed by blinded administration of placebo following a period of treatment with active medication. Habituation effects (tolerance), or sensitization effects (increased response), which require only repeated exposure to a stimulus, might be evidenced after repeated courses of antidepressant treatment. Knowledge of how learning processes impact neurophysiologic response to successive courses of antidepressant treatment would have relevance for clinical populations. Specific hypotheses, however, may be tested in healthy non-clinical samples to avoid potential confounding factors related to severity or chronicity of illness. Learning theories would suggest two hypotheses: (1) neurophysiologic response to placebo will differ between subjects who were previously treated with antidepressant treatment as compared to placebo (classical conditioning hypothesis); and (2) neurophysiologic response to an initial course of antidepressant treatment will differ from response to a repeated course of antidepressant treatment.
|
Depression
| null | 2
|
arm 1: Subjects who had previously been exposed to active antidepressant medication (venlafaxine) arm 2: Subjects who had previously been exposed to placebo only (and never to active antidepressant medication)
|
[
0,
2
] | 1
|
[
0
] |
intervention 1: venlafaxine IR 150mg
|
intervention 1: venlafaxine
| 1
|
Los Angeles | California | United States | -118.24368 | 34.05223
| 0
|
NCT00634283
|
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