Bayesian Dose Adjustment of Immunosuppressants After Lung Transplantation (BASALT)

This study has been terminated.
Sponsor:
Information provided by:
University Hospital, Limoges
ClinicalTrials.gov Identifier:
NCT00975663
First received: September 10, 2009
Last updated: April 23, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Lung and Heart-lung Transplantation
Drug: Tacrolimus and MMF
Phase 4

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:
  • Immunosuppressive treatment failure [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy score [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ] [ Designated as safety issue: Yes ]
  • Toxicity score [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ] [ Designated as safety issue: Yes ]
  • Benefit/risk ratio [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ] [ Designated as safety issue: Yes ]
  • Each event composing the composite criterion [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ] [ Designated as safety issue: Yes ]
  • Overall cost of patients monitoring [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ] [ Designated as safety issue: Yes ]
  • Pharmacogenetic and proteomic analysis [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 180
Study Start Date: September 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Optimized TDM of tacrolimus and MMF dosing
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.
Active Comparator: 2
Current tacrolimus and MMF dosing strategies
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00975663

Locations
Belgium
Service de Pneumologie
Bruxelles, Belgium
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 - Phtisiologie - Hôpital Bichat
Paris, France
Service de Pneumologie - CH de Suresnes
Paris, France
Service de Pneumologie - CHU de Strasbourg
Strasbourg, France
Sponsors and Collaborators
University Hospital, Limoges
Investigators
Study Director: Pierre MARQUET, MD CHU Limoges
  More Information

No publications provided

Responsible Party: Marie SENGELEN, CHU Limoges
ClinicalTrials.gov Identifier: NCT00975663     History of Changes
Other Study ID Numbers: I07038
Study First Received: September 10, 2009
Last Updated: April 23, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Limoges:
Lung transplantation
heart-lung transplantation
therapeutic drug monitoring
tacrolimus
mycophenolate
immunosuppressant
pharmacokinetics

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014