Clinical trial NCT00975663: Bayesian Dose Adjustment of Immunosuppressants After Lung Transplantation
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Lung and Heart-lung Transplantation
Keywords: Lung transplantation
heart-lung transplantation
therapeutic drug monitoring
tacrolimus
mycophenolate
immunosuppressant
pharmacokinetics
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2009-09-11
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

* Male and female patients aged 18 years or more
* CF and non-CF patients receiving single-lung or double-lung or heart-lung transplantation for the first time
* Patients on oral tacrolimus and MMF for at least 48 hours at the time of inclusion (administration via a naso-gastric tube possible if necessary)
* Patients without progressive chronic pathology jeopardizing short term patient and graft survival
* Patients accepting to comply with at least the evaluation visits planned in the investigation center over the first three years post-transplantation (D7, D14, M1, M3, M6, M12, M18, M24, M30, M36)
* Patients giving their free and informed written consent to participate in this study
* Patients with a health insurance policy or registered under a health insurance program

Exclusion Criteria:

* 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

Primary outcomes:
measure: Immunosuppressive treatment failure
timeFrame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
Secondary outcomes:
measure: Efficacy score
timeFrame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
measure: Toxicity score
timeFrame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
measure: Benefit/risk ratio
timeFrame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
measure: Each event composing the composite criterion
timeFrame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
measure: Overall cost of patients monitoring
timeFrame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
measure: Pharmacogenetic and proteomic analysis
timeFrame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Service de Pneumologie
city: Grenoble
country: France
facility: Pôle Médecine Aiguë et Communautaire, Clinique de Pneumologie,
city: Lyon
country: France
facility: Service de Pneumologie, HCL Lyon
city: Marseille
country: France
facility: ApHm -Chirurgie thoracique
city: Nantes
country: France
facility: Service de Pneumologie-CHU de Nantes
city: Paris
country: France
facility: Service de Chirurgie Cardiovasculaire - Hôpital Georges Pompidou
city: Paris
country: France
facility: Service de Pneumologie - CH de Suresnes
city: Paris
country: France
facility: Service de Pneumologie - Phtisiologie - Hôpital Bichat
city: Strasbourg
country: France
facility: Service de Pneumologie - CHU de Strasbourg
Study officials:
affiliation: CHU Limoges
name: Pierre MARQUET, MD
role: STUDY_DIRECTOR
References: