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

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.

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Key information

Conditions

Liver Transplantation

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

CHU de Besançon, Besançon, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Mycophénolate Mofétil

Drug

Ciclosporine A

Drug

Tacrolimus

Drug

Primary outcomes

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).

Sponsors and collaborators

Lead sponsor

University Hospital, Limoges

Other

Registry information

Official study 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

Acronym: MONOCEPT

Important dates

Study start: 2006
Primary completion: 2009
Study completion: 2011
First posted: Apr 4, 2007
Registry last updated: Apr 17, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed