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

Purpose

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.

Condition	Intervention	Phase
Liver Transplantation	Drug: Mycophénolate Mofétil Drug: Ciclosporine A Drug: Tacrolimus	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Interruption of the Calcineurine Inhibitors (ICN) and Introduction of Mycophenolate Mofetil (MMF) in Liver Transplant Patients With Side Effects Due to ICN: Study of the Reduction of the Risks of Rejection by Mycophenolate Mofetil Therapeutic Drug Monitoring

Resource links provided by NLM:

MedlinePlus related topics: Liver Transplantation

Drug Information available for: Mycophenolic acid Mycophenolate sodium Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate mofetil

U.S. FDA Resources

Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:

Incidence of biopsy proven acute rejection treated [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Incidence of biopsy proven acute rejection treated with corticoids or requiring a re-introduction of ICN in arm 1 -- or an increase of ICN in arm 2 -- 6 months after the interruption of ICN (arm 1) or after randomization (arm 2).

Enrollment:	92
Study Start Date:	September 2006
Study Completion Date:	September 2011
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: adjument MMF adjusting the dose according to the MMF AUC of mycophenolic acid	Drug: Mycophénolate Mofétil Drug: Ciclosporine A Drug: Tacrolimus
Active Comparator: continued treatment Continued treatment empirically usual	Drug: Mycophénolate Mofétil Drug: Ciclosporine A Drug: Tacrolimus

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00456235

Locations

France
CHU de Besançon
Besancon, France, 25030
CHU de Bordeaux
Bordeaux, France, 33076
CHU de Caen
Caen, France, 14033
Hôpital Beaujon
Clichy, France, 92000
Hôpital Henri Mondor
Creteil, France, 94010
CHU de Grenoble
Grenoble, France, 38043
CHU de Lille
Lille, France, 59000
Hôpital Edouard Herriot
Lyon, France, 69437
CHU de Marseille
Marseille, France, 13385
CHU de Montpellier
Montpellier, France, 34295
CHU de Nice
Nice, France, 06200
Hôpital Cochin
Paris, France, 75014
Hôpital Saint Antoine
Paris, France, 75012
CHU de Rennes
Rennes, France, 35033
CHU de Strasbourg
Strasbourg, France, 67098
CHU de Toulouse
Toulouse, France, 31059
Hôpital Paul Brousse
Villejuif, France, 94804

Sponsors and Collaborators

University Hospital, Limoges

Investigators

Principal Investigator:

Pierre MARQUET, MD

CHU Limoges

More Information

No publications provided

Responsible Party:	University Hospital, Limoges
ClinicalTrials.gov Identifier:	NCT00456235 History of Changes
Other Study ID Numbers:	I06024
Study First Received:	April 3, 2007
Last Updated:	April 16, 2013
Health Authority:	France : AFSSAPS

Additional relevant MeSH terms:

Mycophenolate mofetil
Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013

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