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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00456235
Recruitment Status : Completed
First Posted : April 4, 2007
Last Update Posted : April 17, 2013
Information provided by (Responsible Party):
University Hospital, Limoges

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.

Condition or disease Intervention/treatment Phase
Liver Transplantation Drug: Mycophénolate Mofétil Drug: Ciclosporine A Drug: Tacrolimus Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : September 2006
Actual Primary Completion Date : September 2009
Actual Study Completion Date : September 2011

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Incidence of biopsy proven acute rejection treated [ Time Frame: 6 months ]
    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).

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00456235

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 Saint Antoine
Paris, France, 75012
Hôpital Cochin
Paris, France, 75014
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
Principal Investigator: Pierre MARQUET, MD CHU Limoges

Responsible Party: University Hospital, Limoges Identifier: NCT00456235     History of Changes
Other Study ID Numbers: I06024
First Posted: April 4, 2007    Key Record Dates
Last Update Posted: April 17, 2013
Last Verified: April 2007

Additional relevant MeSH terms:
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Dermatologic Agents
Antirheumatic Agents