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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges
ClinicalTrials.gov Identifier:
NCT00456235
First received: April 3, 2007
Last updated: April 16, 2013
Last verified: April 2007

April 3, 2007
April 16, 2013
September 2006
September 2009   (final data collection date for primary outcome measure)
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).
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).
Complete list of historical versions of study NCT00456235 on ClinicalTrials.gov Archive Site
Not Provided
  • 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.
Not Provided
Not Provided
 
Reduction in the Risk of Rejection by Mycophenolate Mofetil Dose Adjustment in Liver Transplant Patients With Side Effects Caused by the Calcineurine Inhibitors
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

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Liver Transplantation
  • Drug: Mycophénolate Mofétil
  • Drug: Ciclosporine A
  • Drug: Tacrolimus
  • Experimental: adjument MMF
    adjusting the dose according to the MMF AUC of mycophenolic acid
    Interventions:
    • Drug: Mycophénolate Mofétil
    • Drug: Ciclosporine A
    • Drug: Tacrolimus
  • Active Comparator: continued treatment
    Continued treatment empirically usual
    Interventions:
    • Drug: Mycophénolate Mofétil
    • Drug: Ciclosporine A
    • Drug: Tacrolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
92
September 2011
September 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00456235
I06024
Not Provided
University Hospital, Limoges
University Hospital, Limoges
Not Provided
Principal Investigator: Pierre MARQUET, MD CHU Limoges
University Hospital, Limoges
April 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP