Evaluation of the Benefit/Risk Ratio of a Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil on the Prevention of Complications in Adult Liver Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 195
- 试验地点
- 8
- 主要终点
- Onset of acute rejection (criterion evaluating the risk)
研究概览
简要总结
The prevention of graft rejection after liver transplantation benefits nowadays from a variety of newly developed immunosuppressive agents. This allows more flexible and individualized immunoprophylaxis and gives an opportunity to reduce the long-term side effects (hypertension, renal failure, diabetes, etc.) of immunosuppression. The purpose of this study is to evaluate, in liver transplanted patients, if low doses of tacrolimus, given in combination with mycophenolate mofetil, can result in a lower rate of long-term side effects without increasing the rate of graft rejection.
详细描述
Tacrolimus and mycophenolate mofetil are currently approved immunosuppressive agents for the prevention of acute and chronic rejection in liver transplantation. Adverse effects of tacrolimus are dose-dependent and appear early after the onset of treatment. To prevent side effects, we propose to combine reduced doses of tacrolimus with another immunosuppressant, i.e. mycophenolate mofetil, administered at usual doses. This study evaluates the interest of this combination and, subsequently, the pharmacokinetics of mycophenolate mofetil in this therapeutic context. Patients undergoing liver transplantation will be randomized to tacrolimus at normal doses or to the combination of tacrolimus at half doses and mycophenolate mofetil. A corticotherapy will be associated in both groups. The safety will be evaluated on the number of graft rejections between day 1 after transplantation and week 48; the onset of complications (hypertension, renal failure, diabetes, etc.) will allow to evaluate the efficacy of both treatment schedules.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults over 18 years of age
- •Primary liver transplantation
- •Immunosuppressive treatment associating tacrolimus and steroids at low doses (< 20 mg/d)
- •Written informed consent
- •Non-Inclusion Criteria:
- •Pregnancy or ineffective contraception
- •Immunosuppressive treatment
- •Blood group incompatibility with the donor
- •Autoimmune hepatitis
- •Fulminant hepatitis
- •Primary sclerosing cholangitis
- •Combined transplantations
- •Reduced liver
- •Living donor
- •Treated hypertension and/or diastolic pressure ≥ 90 mmHg and/or systolic pressure ≥ 140 mmHg,
- •Acute or chronic renal failure(creatininemia ≥ 130 μmol/L) before transplantation
- •Treated diabetes and/or fasting glycemia ≥ 7 mmol/L
- •Treated hypercholesterolemia and/or cholesterolemia ≥ 7 mmol/L
- •post-operative creatininemia ≥ 200 μmol/L
排除标准
- 未提供
研究组 & 干预措施
MMF+FK
Low doses of tacrolimus in association with mycophenolate mofetil
干预措施: Mycophenolate mofetil (Drug)
MMF+FK
Low doses of tacrolimus in association with mycophenolate mofetil
干预措施: Tacrolimus (Drug)
FK
Full recommended doses of tacrolimus
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Onset of acute rejection (criterion evaluating the risk)
时间窗: between Day 1 and Week 48
Onset of at least one complication (hypertension, renal failure, diabetes) requiring a specific treatment (criterion evaluating the benefit)
时间窗: between Week 9 and Week 48
次要结局
- Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil(between Day 1 and Week 48)