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

Liver Transplantation Clinical Trial

— MONOCEPT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00456235
• Other study ID #: I06024
• Status: Completed
• Phase: Phase 4
• First received: April 3, 2007
• Last updated: April 16, 2013
• Start date: September 2006
• Est. completion date: September 2011

Study information

• Verified date: April 2007
• Source: University Hospital, Limoges
• Contact: n/a
• Is FDA regulated: No
• Health authority: France : AFSSAPS
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: September 2011
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Drug:
• Mycophénolate Mofétil

• Ciclosporine A

• Tacrolimus

Locations

Country	Name	City	State
France	CHU de Besançon	Besancon
France	CHU de Bordeaux	Bordeaux
France	CHU de Caen	Caen
France	Hôpital Beaujon	Clichy
France	Hôpital Henri Mondor	Creteil
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 Cochin	Paris
France	Hôpital Saint Antoine	Paris
France	CHU de Rennes	Rennes
France	CHU de Strasbourg	Strasbourg
France	CHU de Toulouse	Toulouse
France	Hôpital Paul Brousse	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of biopsy proven acute rejection treated	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).	6 months	Yes