Bayesian Dose Adjustment of Immunosuppressants After Lung Transplantation (BASALT)

• ClinicalTrials.gov Identifier: NCT00975663
• Recruitment Status: Terminated
• First Posted: September 11, 2009
• Last Update Posted: April 26, 2011
• Sponsor: University Hospital, Limoges
• Information provided by: University Hospital, Limoges

Tracking Information

• First Submitted Date: September 10, 2009
• First Posted Date: September 11, 2009
• Last Update Posted Date: April 26, 2011
• Study Start Date: September 2009
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 10, 2009): Immunosuppressive treatment failure [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 10, 2009)

• Efficacy score [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ]
• Toxicity score [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ]
• Benefit/risk ratio [ Time Frame: 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 [ Time Frame: Day 7, day 14, day 21; months 3, 6 and every six months afterwards up to 3 years posttransplantation ]
• 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 ]
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.

Study Arms

• Experimental: 1
  Optimized TDM of tacrolimus and MMF dosing
  Intervention: Drug: Tacrolimus and MMF
• Active Comparator: 2
  Current tacrolimus and MMF dosing strategies
  Intervention: Drug: Tacrolimus and MMF

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Estimated Enrollment (submitted: September 10, 2009): 180
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France

Administrative Information

• NCT Number: NCT00975663
• Other Study ID Numbers: I07038
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Marie SENGELEN, CHU Limoges
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Limoges
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pierre MARQUET, MD; CHU Limoges

• PRS Account: University Hospital, Limoges
• Verification Date: April 2011