NCT00456235

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
92

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Sep 2006

Longer than P75 for phase_4

Geographic Reach
1 country

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2006

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

April 3, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 4, 2007

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2009

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2011

Completed
Last Updated

April 17, 2013

Status Verified

April 1, 2007

Enrollment Period

3 years

First QC Date

April 3, 2007

Last Update Submit

April 16, 2013

Conditions

Liver Transplantation

Outcome Measures

Primary Outcomes (1)

  • 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

Study Arms (2)

adjument MMF

EXPERIMENTAL

adjusting the dose according to the MMF AUC of mycophenolic acid

Drug: Mycophénolate MofétilDrug: Ciclosporine ADrug: Tacrolimus

continued treatment

ACTIVE COMPARATOR

Continued treatment empirically usual

Drug: Mycophénolate MofétilDrug: Ciclosporine ADrug: Tacrolimus

Interventions

Mycophénolate MofétilDRUG
adjument MMFcontinued treatment
Ciclosporine ADRUG
adjument MMFcontinued treatment
TacrolimusDRUG
adjument MMFcontinued treatment

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • Counter-indications to MMF (anaemia, leucopenia)
  • Immunosuppression by sirolimus, everolimus, azathioprine or corticoids

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

CHU de Besançon

Besançon, 25030, France

Location

CHU de Bordeaux

Bordeaux, 33076, France

Location

CHU de Caen

Caen, 14033, France

Location

Hôpital Beaujon

Clichy, 92000, France

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHU de Lille

Lille, 59000, France

Location

Hôpital Edouard Herriot

Lyon, 69437, France

Location

CHU de Marseille

Marseille, 13385, France

Location

CHU de Montpellier

Montpellier, 34295, France

Location

CHU de Nice

Nice, 06200, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

Hôpital Cochin

Paris, 75014, France

Location

CHU de Rennes

Rennes, 35033, France

Location

CHU de Strasbourg

Strasbourg, 67098, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

Hôpital Paul Brousse

Villejuif, 94804, France

Location

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic Chemicals

Study Officials

  • Pierre MARQUET, MD

    CHU Limoges

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 3, 2007

First Posted

April 4, 2007

Study Start

September 1, 2006

Primary Completion

September 1, 2009

Study Completion

September 1, 2011

Last Updated

April 17, 2013

Record last verified: 2007-04

Locations

FR(17)