Bayesian Dose Adjustment of Immunosuppressants After Lung Transplantation
- Registration Number
- NCT00975663
- Lead Sponsor
- University Hospital, Limoges
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 180
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Tacrolimus and MMF Optimized TDM of tacrolimus and MMF dosing 2 Tacrolimus and MMF Current tacrolimus and MMF dosing strategies
- Primary Outcome Measures
Name Time Method Immunosuppressive treatment failure Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (9)
Service de Pneumologie, HCL Lyon
🇫🇷Lyon, France
Service de Pneumologie - CHU de Strasbourg
🇫🇷Strasbourg, France
Service de Pneumologie-CHU de Nantes
🇫🇷Nantes, France
Service de Pneumologie - Phtisiologie - Hôpital Bichat
🇫🇷Paris, France
ApHm -Chirurgie thoracique
🇫🇷Marseille, France
Service de Pneumologie - CH de Suresnes
🇫🇷Paris, France
Pôle Médecine Aiguë et Communautaire, Clinique de Pneumologie,
🇫🇷Grenoble, France
Service de Chirurgie Cardiovasculaire - Hôpital Georges Pompidou
🇫🇷Paris, France
Service de Pneumologie
🇧🇪Bruxelles, Belgium