Evaluation of the Interest of Therapeutic Drug Monitoring of Immunosuppressants (Tacrolimus, Mycophenolate Mofetil) Based on Bayesian Estimation During the Three First Years Following Lung Transplantation, in Patients With or Without Cystic Fibrosis
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 180
- 试验地点
- 9
- 主要终点
- Immunosuppressive treatment failure
研究概览
简要总结
The purpose of this study is to evaluate in lung or heart-lung transplant patients on tacrolimus and mycophenolate the impact of optimized mofetil (MMF) therapeutic drug monitoring and dose adjustment of both drugs on the incidence of treatment failure over the first three years post-transplantation.
详细描述
This research will be based on a prospective randomized trial comparing optimized TDM of tacrolimus and MMF to the current strategy of tacrolimus and MMF dose adjustment in lung transplant recipients. The study will focus on the first three years post-transplantation, as treatment failures (including BOS) occur mainly during this post-transplantation period. As the aim of tacrolimus and MMF dose individualization is to avoid over- or underexposure, for the purpose of this study treatment failure will be a composite criterion gathering events which reflect both over- and underexposure to tacrolimus and MMF.
Optimized TDM of tacrolimus and MMF based on blood tacrolimus and plasma MPA AUC Bayesian estimation will be compared to current strategies: tacrolimus dose adjustment based on trough levels (C0) and administration of a standard dose of MMF, decreased by the pulmonologist in case of adverse drug reactions or increased in case of inefficacy. The efficacy of optimized strategy vs. current strategies will be mainly evaluated through the incidence of treatment failure.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients aged less than 18 years or patients over 18 years under guardianship
- •Patients who disagree with this research
- •Patients with a contra-indication to receiving tacrolimus or MMF
- •Patients on cyclosporine, sirolimus or everolimus
- •Patients who have already benefited from a solid organ transplantation in the past (including lung or heart-lung transplantation)
- •Patients infected by Burkholderia cenocepacia (Burkholderia cepacia genomovar III)
- •Patients receiving HIV protease inhibitors (major pharmacokinetic interaction with tacrolimus)
- •Pregnant or breastfeeding women or those of child-bearing age who do not use an efficient contraceptive method
- •Drug users or patients suffering from neuro-psychiatric disorders preventing them from both proper comprehension of the protocol and reliable consent
- •Patients already participating in another interventional clinical trial
研究组 & 干预措施
1
Optimized TDM of tacrolimus and MMF dosing
干预措施: Tacrolimus and MMF (Drug)
2
Current tacrolimus and MMF dosing strategies
干预措施: Tacrolimus and MMF (Drug)
结局指标
主要结局
Immunosuppressive treatment failure
时间窗: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
次要结局
- Efficacy score(Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation)
- Toxicity score(Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation)
- Benefit/risk ratio(Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation)
- Each event composing the composite criterion(Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation)
- Overall cost of patients monitoring(Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation)
- Pharmacogenetic and proteomic analysis(Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation)