Bayesian Dose Adjustment of Immunosuppressants After Lung Transplantation

Lung and Heart-lung Transplantation Clinical Trial

— BASALT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00975663
• Other study ID #: I07038
• Status: Terminated
• Phase: Phase 4
• First received: September 10, 2009
• Last updated: April 23, 2011
• Start date: September 2009
• Est. completion date: February 2011

Study information

• Verified date: April 2011
• Source: University Hospital, Limoges
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 180
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung and Heart-lung Transplantation

Intervention

Drug:
• Tacrolimus and MMF
Tacrolimus: daily oral dose divided into 2 doses (morning and evening). MMF: daily dose divided into 2 doses at 12 hour intervals or 3 doses at 8 hour intervals.
• Tacrolimus and MMF
Tacrolimus: daily oral dose divided into 2 doses (morning and evening). MMF: daily dose divided into 2 doses at 12 hour intervals or 3 doses at 8 hour intervals.

Locations

Country	Name	City	State
Belgium	Service de Pneumologie	Bruxelles
France	Pôle Médecine Aiguë et Communautaire, Clinique de Pneumologie,	Grenoble
France	Service de Pneumologie, HCL Lyon	Lyon
France	ApHm -Chirurgie thoracique	Marseille
France	Service de Pneumologie-CHU de Nantes	Nantes
France	Service de Chirurgie Cardiovasculaire - Hôpital Georges Pompidou	Paris
France	Service de Pneumologie - CH de Suresnes	Paris
France	Service de Pneumologie - Phtisiologie - Hôpital Bichat	Paris
France	Service de Pneumologie - CHU de Strasbourg	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunosuppressive treatment failure		Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation	Yes
Secondary	Efficacy score		Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation	Yes
Secondary	Toxicity score		Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation	Yes
Secondary	Benefit/risk ratio		Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation	Yes
Secondary	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	Yes
Secondary	Overall cost of patients monitoring		Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation	Yes
Secondary	Pharmacogenetic and proteomic analysis		Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation	Yes