A Double-Blind, Placebo -Controlled, Randomized Study to Assess the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplantation.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 434
- 主要终点
- Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant
研究概览
简要总结
The purpose of the study is to compare the number of randomized participants in each treatment group who experience an acute rejection episode in the first 6 months after undergoing cardiac transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be undergoing their first cardiac allograft transplant
- •Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to transplantation
- •Women of childbearing potential must use two reliable forms of contraception simultaneously. Effective contraception must be used before beginning study drug therapy, and for 4 months following discontinuation of study drug therapy
- •Participants and/or their guardians must be willing and be capable of understanding risks and comply with the purpose of the study
排除标准
- •Previous organ transplants
- •Participants receiving multiple organs
- •Participants requiring ventricular assist device (VAD) upon completion of transplantation surgery
- •Women lactating, pregnant or of childbearing potential not using, or who are unwilling to use two reliable forms of contraception simultaneously during the study
- •History of a psychological illness or condition which would interfere with the participant's ability to understand the requirements of the study
- •White blood count =<2500/mm^3, platelets =<50,000/mm^3 or hemoglobin =<6 g/dL
- •HIV-1, the presence of positive HBsAg, or chronic active hepatitis C
- •Active peptic ulcer disease
- •Severe diarrhea or other gastrointestinal disorders which might interfere with their ability to absorb oral medication
- •Malignancies within the past 5 years, excluding skin carcinoma that have been adequately treated
- •Participants who have received within the past 30 days or require concomitant treatment with other investigational drugs or immunosuppressive medications that are prohibited for this study
- •Inability to start microemulsion form of cyclosporine within 72 hours
研究组 & 干预措施
Daclizumab
Daclizumab will be administered as a intravenous dose of 1 milligrams per kilogram [mg/kg] on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg, and 500-1000 mg IV methylprednisolone peri operative switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: Daclizumab (Drug)
Daclizumab
Daclizumab will be administered as a intravenous dose of 1 milligrams per kilogram [mg/kg] on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg, and 500-1000 mg IV methylprednisolone peri operative switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: Methylprednisolone (Drug)
Daclizumab
Daclizumab will be administered as a intravenous dose of 1 milligrams per kilogram [mg/kg] on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg, and 500-1000 mg IV methylprednisolone peri operative switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: Mycophenolate mofetil (Drug)
Daclizumab
Daclizumab will be administered as a intravenous dose of 1 milligrams per kilogram [mg/kg] on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg, and 500-1000 mg IV methylprednisolone peri operative switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: cyclosporine (Drug)
Placebo
Matching placebo will be administered on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg orally, and 500-1000 mg IV methylprednisolone peri-op switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: Methylprednisolone (Drug)
Placebo
Matching placebo will be administered on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg orally, and 500-1000 mg IV methylprednisolone peri-op switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: Mycophenolate mofetil (Drug)
Placebo
Matching placebo will be administered on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg orally, and 500-1000 mg IV methylprednisolone peri-op switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: Placebo (Drug)
Placebo
Matching placebo will be administered on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg orally, and 500-1000 mg IV methylprednisolone peri-op switch to oral at 0.5-1 mg/kg/day followed by tapering.
干预措施: cyclosporine (Drug)
结局指标
主要结局
Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant
时间窗: Up to 6 months PT
The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months post-transplant (PT). Participants with acute rejection included participants with a biopsy histology of International Society of Heart and Lung Transplant (ISHLT) Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up.
次要结局
- Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT(Within 6 months and 12 months PT)
- Number of Participants Who Developed Acute Rejection Episode Within the 12 Months PT(Up to 12 months PT)
- Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT(Within 6 months and 12 months PT)
- Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT(At 6 months, 12 months , 3 years PT)
- Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT(Within 6 months and 12 months PT)
- Number of Participants Using Monomurab Cluster of Differentiation 3, Orthoclone Polyclonal Antithymocyte Globulin or Antilymphocyte Globulin in the First 6 Months and 12 Months PT(Within 6 months and 12 months PT)
- Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT(Within 6 months and 12 months PT)
- Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides)(From Baseline (Day -2) to 3 months and 6 months)
- Median Change From Baseline for LDL/HDL Ratio(From Baseline (Day -2) to 3 months, and 6 months)
- Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters(Up to 12 months)
- Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters(Up to 12 months)
- Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal(Up to 12 months)
- Number of Participants With Malignancies and Opportunistic Infections(Up to 12 months)