Interruption of the Calcineurine Inhibitors (ICN) and Introduction of Mycophenolate Mofetil (MMF) in Liver Transplant Patients With Side Effects Due to ICN: Study of the Reduction of the Risks of Rejection by Mycophenolate Mofetil Therapeutic Drug Monitoring
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 92
- 试验地点
- 17
- 主要终点
- Incidence of biopsy proven acute rejection treated
研究概览
简要总结
The aim of this project is to determine whether, in liver transplant patients with side effects due to ICN, the use of MMF in monotherapy can be optimised by dose adjustment based on the area under the curve (AUC) of mycophenolic acid (MPA). It involves a multicentre phase IV trial with direct individual benefit.
A population of 130 liver transplant patients at 2 to 10 years post-transplant, showing significant clinical ICN side effects and being given bitherapy by ICN +MMF will be included and randomised 1:1 in two arms:
- Arm 1: progressive interruption of ICN after obtaining an AUC of MPA of 50 mg.h/l, followed by MMF monotherapy with dose adjustment based on the AUC of MPA,
- Arm 2: continuation of the ICN+MMF bitherapy without MMF therapeutic drug monitoring.
The main judgement criterion will be the incidence of acute rejection in the 2 groups at 6 months. The secondary judgment criterion will be the evaluation of the benefit of stopping ICN on the side effects caused by these drugs.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with first liver transplantion or retransplantation since more than 6 months: with a post-transplant lapse of time of 2 to 10 years and showing one of the following adverse effects of ICN:
- •Renal insufficiency defined by a creatinine clearance <50ml/mn (calculated or estimated according to the Cockcroft formula)
- •Arterial hypertension not controlled by an anti-hypertensive bitherapy
- •Diabetes mellitus (fasting glycaemia >7.0mmol/l), whether treated or not
- •Neuromuscular toxicity
- •Immunosuppression by cyclosporine or tacrolimus and MMF
- •Hepatic biopsy performed within the 6 months preceding the inclusion for the patients with a post-transplant period of <5 years and in the 12 months preceding the inclusion for patients with a post transplant period of >5 years.
排除标准
- •Acute rejection within the 6 months preceding the screening
- •Previous history of cortico-resistant rejection
- •Chronic rejection
- •Significant ductopenia (absence of inter-lobule biliary canals in more than 30% of the portal tracts) on the pre-screening biopsy.
- •Existence of a pre-transplantation diabetes mellitus.
- •Liver transplantation for auto-immune hepatitis or primary sclerosing cholangitis
- •Patients transplanted for viral C cirrhosis with reinfection lesions of the transplanted organ, rendering treatment by ribarivine + interferon conceivable in the year following inclusion.
- •Counter-indications to MMF (anaemia, leucopenia)
- •Immunosuppression by sirolimus, everolimus, azathioprine or corticoids
研究组 & 干预措施
adjument MMF
adjusting the dose according to the MMF AUC of mycophenolic acid
干预措施: Mycophénolate Mofétil (Drug)
adjument MMF
adjusting the dose according to the MMF AUC of mycophenolic acid
干预措施: Ciclosporine A (Drug)
adjument MMF
adjusting the dose according to the MMF AUC of mycophenolic acid
干预措施: Tacrolimus (Drug)
continued treatment
Continued treatment empirically usual
干预措施: Mycophénolate Mofétil (Drug)
continued treatment
Continued treatment empirically usual
干预措施: Ciclosporine A (Drug)
continued treatment
Continued treatment empirically usual
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Incidence of biopsy proven acute rejection treated
时间窗: 6 months
Incidence of biopsy proven acute rejection treated with corticoids or requiring a re-introduction of ICN in arm 1 -- or an increase of ICN in arm 2 -- 6 months after the interruption of ICN (arm 1) or after randomization (arm 2).
次要结局
未报告次要终点