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

Sponsored by:	University Hospital, Limoges
Information provided by:	University Hospital, Limoges
ClinicalTrials.gov Identifier:	NCT00456235

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 IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics Study
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: Tacrolimus anhydrous 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 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).

Secondary Outcome Measures:

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 -- 12 months after the interruption of ICN (arm 1) or after randomization (arm 2).
Incidence of a composite end-point at 12 months, associating biopsy proven acute rejection treated with corticoids or requiring an increase and a re-introduction of ICN + chronic rejection + re-transplantation + death.
Incidence of histological lesions of acute or chronic rejection at 12 months.
Values of hepatic biological tests in each arm at 12 months.
Evolution of side effects of the ICN in each arm at 12 months.
Incidence of infectious and cancer complications in each arm at 12 months.

Estimated Enrollment:	130
Study Start Date:	September 2006

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

Contacts

Contact: Christophe DUVOUX, MD

(33) 01 49 81 23 53

christophe.duvoux@hmn.aphp.fr

Locations

France
Hôpital Henri Mondor	Recruiting
CRETEIL, France, 94010
Contact: Christophe DUVOUX, MD (33) 01 49 81 23 53 christophe.duvoux@hmn.aphp.fr
Hôpital Cochin	Recruiting
PARIS, France, 75014
Sub-Investigator: Yvon CALMUS, MD
CHU de Rennes	Recruiting
RENNES, France, 35033
Sub-Investigator: Karim BOUDJEMA, MD
Sub-Investigator: Richard LORHO, MD
CHU de Montpellier	Recruiting
MONTPELLIER, France, 34295
Sub-Investigator: Georges PAGEAUX, MD
Hôpital Paul Brousse	Recruiting
VILLEJUIF, France, 94804
Sub-Investigator: Faouzi SALIBA, MD
Hôpital Edouard Herriot	Recruiting
LYON, France, 69437
Sub-Investigator: Jérôme DUMORTIER, MD
CHU de Lille	Recruiting
LILLE, France, 59000
Sub-Investigator: Sébastien DHARANCY, MD
Hôpital Beaujon	Recruiting
CLICHY, France, 92000
Sub-Investigator: François DURAND, MD
Hôpital Saint Antoine	Recruiting
PARIS, France, 75012
Sub-Investigator: Olivier CHAZOUILLERES, MD
CHU de Marseille	Recruiting
MARSEILLE, France, 13385
Sub-Investigator: Yves-Patrice LE TREUT, MD
CHU de Strasbourg	Recruiting
STRASBOURG, France, 67098
Sub-Investigator: Philippe WOLF, MD
CHU de Caen	Recruiting
CAEN, France, 14033
Sub-Investigator: Ephrem SALAME, MD
CHU de Nice	Recruiting
NICE, France, 06200
Sub-Investigator: Jean GUGENHEIM, MD
CHU de Toulouse	Recruiting
TOULOUSE, France, 31059
Sub-Investigator: Lionel ROSTAING, MD
CHU de Besançon	Recruiting
BESANCON, France, 25030
Sub-Investigator: Claire VANLEMNENS, MD
CHU de Grenoble	Recruiting
GRENOBLE, France, 38043
Sub-Investigator: Marie-Noëlle HILLERET, MD
CHU de Bordeaux	Recruiting
BORDEAUX, France, 33076
Sub-Investigator: Martine NEAU-CRANSAC, MD

Sponsors and Collaborators

University Hospital, Limoges

Investigators

Principal Investigator:

Pierre MARQUET, MD

CHU Limoges

More Information

No publications provided

Study ID Numbers:	I06024
Study First Received:	April 3, 2007
Last Updated:	April 3, 2007
ClinicalTrials.gov Identifier:	NCT00456235 History of Changes
Health Authority:	France : AFSSAPS

Study placed in the following topic categories:

Anti-Bacterial Agents
Immunologic Factors
Mycophenolic Acid

Mycophenolate mofetil
Tacrolimus
Immunosuppressive Agents

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Mycophenolic Acid

Mycophenolate mofetil
Enzyme Inhibitors
Tacrolimus
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 02, 2009