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

This study has been terminated.
(insufficient enrollment)
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT00151632
First received: September 8, 2005
Last updated: July 3, 2012
Last verified: July 2012

September 8, 2005
July 3, 2012
May 2003
December 2008   (final data collection date for primary outcome measure)
  • Onset of acute rejection (criterion evaluating the risk) [ Time Frame: between Day 1 and Week 48 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Onset of acute rejection between Day 1 and Week 48 (criterion evaluating the risk)
  • Onset of at least one complication (hypertension, renal failure, diabetes) requiring a specific treatment between Week 9 and Week 48 (criterion evaluating the benefit).
Complete list of historical versions of study NCT00151632 on ClinicalTrials.gov Archive Site
Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil [ Time Frame: between Day 1 and Week 48 ] [ Designated as safety issue: Yes ]
Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil.
Not Provided
Not Provided
 
Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil After Liver Transplantation
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Evidence of Liver Transplantation
  • 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:
    • FK
    • PROGRAF
  • Experimental: MMF+FK
    Low doses of tacrolimus in association with mycophenolate mofetil
    Interventions:
    • Drug: Mycophenolate mofetil
    • Drug: Tacrolimus
  • Active Comparator: FK
    Full recommended doses of tacrolimus
    Intervention: Drug: Tacrolimus

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
195
May 2009
December 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00151632
AFSSAPS 030200, PHRC/01-01, CIC0203/011
Yes
Rennes University Hospital
Rennes University Hospital
Ministry of Health, France
Study Director: Karim Boudjema, MD, PhD CHU Rennes
Study Chair: Eric Bellissant, MD, PhD CHU Rennes
Rennes University Hospital
July 2012

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