A Phase III, Randomized, Open-Label, Comparative, Multi-Center Study to Assess the Safety and Efficacy of Prograf (Tacrolimus)/MMF, Modified Release (MR) Tacrolimus/MMF and Neoral (Cyclosporine)/MMF in de Novo Kidney Transplant Recipients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 668
- 主要终点
- Percentage of Participants With Efficacy Failure
研究概览
简要总结
The purpose of this study is to compare the safety and efficacy of tacrolimus/mycophenolate mofetil (MMF), cyclosporine/MMF and tacrolimus modified release/MMF in de novo kidney transplant recipients.
详细描述
This was a 3 arm randomized, open-label, comparative, multi-center study in de novo kidney transplant recipients at 60 centers in the U.S., Canada and Brazil.
The study consisted of a 1-year post-transplant efficacy and safety study with a clinical continuation phase of a minimum of 2 years or until commercial availability of tacrolimus modified release, unless the Data Safety Monitoring Board or sponsor specified otherwise.
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
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient of a primary or retransplanted non-human leukocyte antigen (HLA)-identical living or non-HLA-identical cadaveric kidney transplant
- •Age greater or equal to 12 years
排除标准
- •Recipient or donor is known seropositive for human immunodeficiency virus (HIV)
- •Has current malignancy or history of malignancy
- •Has significant liver disease
- •Has uncontrolled concomitant infection or any other unstable medical condition
- •Is receiving everolimus or enteric coated mycophenolic acid at any time during the study
- •Received kidney with a cold ischemia time of equal or more than 36 hours
- •Received kidney transplant from a cadaveric donor equal or more than 60 years of age
- •Received intravenous immunoglobulin (IVIG) therapy prior to randomization
研究组 & 干预措施
Tacrolimus
Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
干预措施: Tacrolimus (Drug)
Tacrolimus
Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
干预措施: mycophenolate mofetil (Drug)
Tacrolimus Modified Release
Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
干预措施: Tacrolimus Modified Release (MR) (Drug)
Tacrolimus Modified Release
Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
干预措施: mycophenolate mofetil (Drug)
Cyclosporine
Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
干预措施: cyclosporine microemulsion (Drug)
Cyclosporine
Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
干预措施: mycophenolate mofetil (Drug)
结局指标
主要结局
Percentage of Participants With Efficacy Failure
时间窗: one year
Efficacy failure is defined as any participant who died, experienced a graft failure (permanent return to dialysis \[\> 30 days\] or retransplant), had a biopsy-confirmed (Banff Grade ≥ I) acute rejection (BCAR), or was lost to follow-up. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
次要结局
- Graft Survival at One Year(One year)
- Patient Survival at One Year(One year)
- Percentage of Participants With Biopsy Confirmed Acute Rejection at 6 and 12 Months(Six months and 12 months)
- Time to First Biopsy-confirmed Acute Rejection Episode(one year)
- Number of Participants Requiring Anti-lymphocyte Antibody Therapy for Treatment of Rejection(one year)
- Severity of Acute Rejection(one year)
- Number of Participants Experiencing Multiple Rejection Episodes(one year)
- Number of Participants With Clinically Treated Acute Rejection Episodes(one year)
- Number of Participants With Treatment Failure(one year)
- Number of Participants Who Crossed Over Due to Treatment Failure(one year)
- Change From Month 1 in Serum Creatinine at Month 6 and Month 12(Month 1, Month 6, and Month 12)
- Change From Month 1 in Creatinine Clearance at Month 6 and Month 12(Month 1, Month 6, and Month 12)
- Kaplan-Meier Estimate of Patient Survival at the End of the Study(End of study (maximum time on study was 1,941 days).)
- Kaplan-Meier Estimate of Graft Survival at the End of the Study(End of study (maximum time on study was 1,941 days).)