Reduction in the Risk of Rejection by Mycophenolate Mofetil Dose Adjustment in Liver Transplant Patients With Side Effects Caused by the Calcineurine Inhibitors

NCT ID: NCT00456235

Last Updated: 2013-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2011-09-30

Brief Summary

The aim of this project is to determine whether, in liver transplant patients with side effects due to ICN, the use of MMF in monotherapy can be optimised by dose adjustment based on the area under the curve (AUC) of mycophenolic acid (MPA). It involves a multicentre phase IV trial with direct individual benefit.

A population of 130 liver transplant patients at 2 to 10 years post-transplant, showing significant clinical ICN side effects and being given bitherapy by ICN +MMF will be included and randomised 1:1 in two arms:

• Arm 1: progressive interruption of ICN after obtaining an AUC of MPA of 50 mg.h/l, followed by MMF monotherapy with dose adjustment based on the AUC of MPA,
• Arm 2: continuation of the ICN+MMF bitherapy without MMF therapeutic drug monitoring.

The main judgement criterion will be the incidence of acute rejection in the 2 groups at 6 months. The secondary judgment criterion will be the evaluation of the benefit of stopping ICN on the side effects caused by these drugs.

Conditions

Liver Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

adjument MMF

adjusting the dose according to the MMF AUC of mycophenolic acid

Group Type: EXPERIMENTAL

Mycophénolate Mofétil

Intervention Type: DRUG

Ciclosporine A

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

continued treatment

Continued treatment empirically usual

Group Type: ACTIVE_COMPARATOR

Mycophénolate Mofétil

Intervention Type: DRUG

Ciclosporine A

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Interventions

Mycophénolate Mofétil

Intervention Type: DRUG

Ciclosporine A

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient with first liver transplantion or retransplantation since more than 6 months: with a post-transplant lapse of time of 2 to 10 years and showing one of the following adverse effects of ICN:
• Renal insufficiency defined by a creatinine clearance <50ml/mn (calculated or estimated according to the Cockcroft formula)
• Arterial hypertension not controlled by an anti-hypertensive bitherapy
• Diabetes mellitus (fasting glycaemia >7.0mmol/l), whether treated or not
• Neuromuscular toxicity
• Immunosuppression by cyclosporine or tacrolimus and MMF
• Hepatic biopsy performed within the 6 months preceding the inclusion for the patients with a post-transplant period of <5 years and in the 12 months preceding the inclusion for patients with a post transplant period of >5 years.

Exclusion Criteria

• Acute rejection within the 6 months preceding the screening
• Previous history of cortico-resistant rejection
• Chronic rejection
• Significant ductopenia (absence of inter-lobule biliary canals in more than 30% of the portal tracts) on the pre-screening biopsy.
• Existence of a pre-transplantation diabetes mellitus.
• Liver transplantation for auto-immune hepatitis or primary sclerosing cholangitis
• Patients transplanted for viral C cirrhosis with reinfection lesions of the transplanted organ, rendering treatment by ribarivine + interferon conceivable in the year following inclusion.
• Counter-indications to MMF (anaemia, leucopenia)
• Immunosuppression by sirolimus, everolimus, azathioprine or corticoids

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Limoges

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre MARQUET, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Limoges

Locations

CHU de Besançon

Besançon, , France

CHU de Bordeaux

Bordeaux, , France

CHU de Caen

Caen, , France

Hôpital Beaujon

Clichy, , France

Hôpital Henri Mondor

Créteil, , France

CHU de Grenoble

Grenoble, , France

CHU de Lille

Lille, , France

Hôpital Edouard Herriot

Lyon, , France

CHU de Marseille

Marseille, , France

CHU de Montpellier

Montpellier, , France

CHU de Nice

Nice, , France

Hôpital Saint Antoine

Paris, , France

Hôpital Cochin

Paris, , France

CHU de Rennes

Rennes, , France

CHU de Strasbourg

Strasbourg, , France

CHU de Toulouse

Toulouse, , France

Hôpital Paul Brousse

Villejuif, , France

Countries

France

Other Identifiers

I06024

Identifier Type: -

Identifier Source: org_study_id