Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil After Liver Transplantation

Phase 3

Terminated

• Conditions: Evidence of Liver Transplantation
• Interventions: Drug: Mycophenolate mofetil; Drug: Tacrolimus

• Registration Number: NCT00151632
• Lead Sponsor: Rennes University Hospital

Brief Summary

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.

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 Timeline

• Study Start: 2003-05
• Study First Submitted: 2005-09-08
• Study First Submitted QC: 2005-09-08
• Study First Posted: 2005-09-09
• Primary Completion: 2008-12
• Study Completion: 2009-05
• Status Verified: 2012-07
• Last Update Submitted: 2012-07-03
• Last Update Posted: 2012-07-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 195

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MMF+FK	Mycophenolate mofetil	Low doses of tacrolimus in association with mycophenolate mofetil
FK	Tacrolimus	Full recommended doses of tacrolimus
MMF+FK	Tacrolimus	Low doses of tacrolimus in association with mycophenolate mofetil

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil	between Day 1 and Week 48

Trial Locations

Locations (8)

Service de Chirurgie Digestive - Hôpital de la Côte de Nacre; 🇫🇷 Caen, France

Service d'Hépatogastroentérologie - Hôpital Beaujon; 🇫🇷 Clichy, France

Service d'Hépatogastroentérologie - Hôpital Henri Mondor; 🇫🇷 Créteil, France

Chirurgie Générale et Digestive - Hôpital de La Croix Rousse; 🇫🇷 Lyon, France

Service de Chirurgie Générale - Hôpital Cochin; 🇫🇷 Paris, France

Service d'Hépaogastroentérologie - Hôpital Saint Eloi; 🇫🇷 Montpellier, France

Département de Chirurgie Viscérale - Hôpital Pontchaillou; 🇫🇷 Rennes, France

Centre Hépato-biliaire - Hôpital Paul Brousse; 🇫🇷 Villejuif, France