Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil After Liver Transplantation (MMF-FK)

July 3, 2012 updated by: Rennes University Hospital

Evaluation of the Benefit/Risk Ratio of a Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil on the Prevention of Complications in Adult Liver Transplantation

The prevention of graft rejection after liver transplantation benefits nowadays from a variety of newly developed immunosuppressive agents. This allows more flexible and individualized immunoprophylaxis and gives an opportunity to reduce the long-term side effects (hypertension, renal failure, diabetes, etc.) of immunosuppression. The purpose of this study is to evaluate, in liver transplanted patients, if low doses of tacrolimus, given in combination with mycophenolate mofetil, can result in a lower rate of long-term side effects without increasing the rate of graft rejection.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Tacrolimus and mycophenolate mofetil are currently approved immunosuppressive agents for the prevention of acute and chronic rejection in liver transplantation. Adverse effects of tacrolimus are dose-dependent and appear early after the onset of treatment. To prevent side effects, we propose to combine reduced doses of tacrolimus with another immunosuppressant, i.e. mycophenolate mofetil, administered at usual doses. This study evaluates the interest of this combination and, subsequently, the pharmacokinetics of mycophenolate mofetil in this therapeutic context. Patients undergoing liver transplantation will be randomized to tacrolimus at normal doses or to the combination of tacrolimus at half doses and mycophenolate mofetil. A corticotherapy will be associated in both groups. The safety will be evaluated on the number of graft rejections between day 1 after transplantation and week 48; the onset of complications (hypertension, renal failure, diabetes, etc.) will allow to evaluate the efficacy of both treatment schedules.

Study Type

Interventional

Enrollment (Actual)

195

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Caen, France, 14033
        • Service de Chirurgie Digestive - Hôpital de la Côte de Nacre
      • Clichy, France, 92110
        • Service d'Hépatogastroentérologie - Hôpital Beaujon
      • Créteil, France, 94010
        • Service d'Hépatogastroentérologie - Hôpital Henri Mondor
      • Lyon, France, 69317
        • Chirurgie Générale et Digestive - Hôpital de La Croix Rousse
      • Montpellier, France
        • Service d'Hépaogastroentérologie - Hôpital Saint Eloi
      • Paris, France, 75679
        • Service de Chirurgie Générale - Hôpital Cochin
      • Rennes, France, 35033
        • Département de Chirurgie Viscérale - Hôpital Pontchaillou
      • Villejuif, France
        • Centre Hépato-Biliaire - Hôpital Paul Brousse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adults over 18 years of age
  • Primary liver transplantation
  • Immunosuppressive treatment associating tacrolimus and steroids at low doses (< 20 mg/d)
  • Written informed consent

Non-Inclusion Criteria:

  • Pregnancy or ineffective contraception
  • Immunosuppressive treatment
  • Blood group incompatibility with the donor
  • Autoimmune hepatitis
  • Fulminant hepatitis
  • Primary sclerosing cholangitis
  • Combined transplantations
  • Reduced liver
  • Living donor
  • Treated hypertension and/or diastolic pressure ≥ 90 mmHg and/or systolic pressure ≥ 140 mmHg,
  • Acute or chronic renal failure(creatininemia ≥ 130 μmol/L) before transplantation
  • Treated diabetes and/or fasting glycemia ≥ 7 mmol/L
  • Treated hypercholesterolemia and/or cholesterolemia ≥ 7 mmol/L
  • post-operative creatininemia ≥ 200 μmol/L

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MMF+FK
Low doses of tacrolimus in association with mycophenolate mofetil
Drug: Mycophenolate mofetil
Mycophenolate mofetil is administered at a dose of 1,5 g x 2 / day for the 6 first weeks, then 1g x 2 / day until M12.
Other Names:
  • MMF
  • CELLCEPT
Drug: Tacrolimus

In arm 1: Tacrolimus is administered at half recommended dose: 0,040 mg/Kg x 2 , in order to maintain plasma levels between 6 and 10 ng/ml for the 6 first weeks, between 5 and 8 ng/ml from week 7 to M6 and between 4 and 6 ng/ml between M6 and M12.

In arm 2: Tacrolimus is administered at the recommended dose: 0,075 mg/Kg x 2 , in order to maintain plasma levels between 12 and 20 ng/ml for the 6 first weeks, between 10 and 15 ng/ml from week 7 to week 12, between 8 and 12 ng/ml between M4 and M6 and between 6 and 10 ng/ml between M6 and M12.

Other Names:
  • PROGRAF
  • FK
Active Comparator: FK
Full recommended doses of tacrolimus
Drug: Tacrolimus

In arm 1: Tacrolimus is administered at half recommended dose: 0,040 mg/Kg x 2 , in order to maintain plasma levels between 6 and 10 ng/ml for the 6 first weeks, between 5 and 8 ng/ml from week 7 to M6 and between 4 and 6 ng/ml between M6 and M12.

In arm 2: Tacrolimus is administered at the recommended dose: 0,075 mg/Kg x 2 , in order to maintain plasma levels between 12 and 20 ng/ml for the 6 first weeks, between 10 and 15 ng/ml from week 7 to week 12, between 8 and 12 ng/ml between M4 and M6 and between 6 and 10 ng/ml between M6 and M12.

Other Names:
  • PROGRAF
  • FK

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Onset of acute rejection (criterion evaluating the risk)
Time Frame: between Day 1 and Week 48
between Day 1 and Week 48
Onset of at least one complication (hypertension, renal failure, diabetes) requiring a specific treatment (criterion evaluating the benefit)
Time Frame: between Week 9 and Week 48
between Week 9 and Week 48

Secondary Outcome Measures

Outcome Measure
Time Frame
Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil
Time Frame: between Day 1 and Week 48
between Day 1 and Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rennes University Hospital

Collaborators

Ministry of Health, France

Investigators

  • Study Director: Karim Boudjema, MD, PhD, Chu Rennes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2003

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 9, 2005

Study Record Updates

Last Update Posted (Estimate)

July 4, 2012

Last Update Submitted That Met QC Criteria

July 3, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFSSAPS 030200
  • PHRC/01-01 (Other Identifier: Rennes University Hospital)
  • CIC0203/011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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