De Novo Everolimus Versus Tacrolimus in Combination With Mofetil Mycophenolate and Low Dose Corticosteroids to Reduce Tacrolimus Induced Nephrotoxicity in Liver Transplantation: a Prospective, Multicentric, Randomised Study
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 主要终点
- Occurrence of graft loss
研究概览
简要总结
Tacrolimus is a calcineurin inhibitor. This is the immunosuppression of reference for patients undergoing a first liver transplant. This treatment can prevent graft rejection, but can cause side effects including kidney failure (in 25% after the first year).
Everolimus is an immunosuppressive that effectively prevents acute rejection in heart and kidney transplant recipients. It preserves renal function when it is started soon after the transplant, i.e. before a severe dysfunction is installed.
详细描述
In the liver transplant, early interruption of calcineurin inhibitors with a quick relay everolimus monotherapy preserves renal function and is associated with a lower acute rejection rate.
We wish to assess whether the introduction of a de novo immunosuppression everolimus under protection of basiliximab induction, mycophenolate mofetil and then low doses of corticosteroids, reduces the nephrotoxicity of immunosuppressive therapy in liver transplant patients, compared to a standard protocol with tacrolimus associated with mycophenolate mofetil and low dose corticosteroids.
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 (≥18 years), male or female,
- •Patients due to receive a first liver transplant with a full or reduced graft taken from a donor brain-dead beating heart or a related living donor,
- •Patients having given a free and informed written consent .
- •Post-transplantation Inclusion criteria: Patients meeting the following criteria will be included:
- •Receiving basiliximab (Simulect)
- •Whose immunosuppression regimen from day 5 could immediately consist of either tacrolimus or everolimus, in combination with mycophenolate mofetil and low dose corticosteroids
- •With hepatic artery permeable to echo Doppler 4 days after transplant.
排除标准
- •History of immunosuppressive therapy,
- •Known hypersensitivity to the treatments or macrolides,
- •HIV infection
- •Autoimmune hepatitis,
- •Primary sclerosing cholangitis,
- •Programming or realization of a combined transplant,
- •Pregnancy or lack of effective contraception,
- •Breastfeeding.
- •Incompatibility with the donor,
- •Thrombosis of the hepatic artery between D0 and D4,
- •Non-primary graft function leading to a re-registration on the waiting list.
研究组 & 干预措施
Tacrolimus group
Tacrolimus + mycophenolate mofetil + corticosteroids
干预措施: Everolimus (Drug)
Tacrolimus group
Tacrolimus + mycophenolate mofetil + corticosteroids
干预措施: Mycophenolate mofetil (Drug)
Tacrolimus group
Tacrolimus + mycophenolate mofetil + corticosteroids
干预措施: Prednisolone, Prednisone or Methylprednisolone (Drug)
Everolimus group
Everolimus + mycophenolate mofetil + corticosteroids
干预措施: Tacrolimus (Drug)
Everolimus group
Everolimus + mycophenolate mofetil + corticosteroids
干预措施: Mycophenolate mofetil (Drug)
Everolimus group
Everolimus + mycophenolate mofetil + corticosteroids
干预措施: Prednisolone, Prednisone or Methylprednisolone (Drug)
结局指标
主要结局
Occurrence of graft loss
时间窗: Between the baseline and the end of the treatment (week 48) (censored criterion
Graft loss , whatever the cause, or thrombosis of the hepatic artery are recorded between baseline and the end of S48 (censored criterion).
Worsening of renal function
时间窗: Between the initiation of treatment (Day 5) and the end (week 48) (censored criterion)
The main objective of the study is to evaluate, in liver transplanted patients, the benefit in terms of prevention of renal failure, a regimen that includes a de novo introduction of everolimus instead of tacrolimus, in combination with mycophenolate mofetil and low doses of corticosteroids, to the extent that this benefit is not accompanied by an increased risk of graft loss or hepatic artery thrombosis. Insofar as the objective of the study is to assess a risk / benefit ratio, the study has two main criteria. Worsening renal function is validated before the prolonged decline (found on at least 3 assays carried out at least 3 months apart) over 30% of the creatinine clearance compared to the value at baseline . The date of the first evidence of this worsening of renal function is the date used to calculate the distribution of censored criterion.
次要结局
- Plasma creatinine(At the end of the treatment (week 48))
- Glomerular filtration rate(At the end of the treatment (week 48))
- Hypertension control(Between the baseline and the end of the treatment (week 48) (censored criterion))
- Occurence of convulsions(Between the baseline and the end of the treatment (week 48) (censored criterion))
- Hypertriglyceridemia(Between the baseline and the end of the treatment (week 48) (censored criterion))
- Number of patients with incident diabetes(Between the baseline and the end of the treatment (week 48) (censored criterion))
- Number of patients with infection(At the end of the treatment (week 48))
- Occurrence of mental trouble(Between the baseline and the end of the treatment (week 48) (censored criterion))
- Hypercholesterolemia(Between the baseline and the end of the treatment (week 48) (censored criterion))
- Number of mycophenolate mofetil linked adverse events(At the end of the treatment (week 48))
- Number of everolimus linked adverse events(At the end of the treatment (week 48))