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

NCT00151632 | Terminated Phase 3 DMC

• 3 other identifiers: AFSSAPS 030200PHRC/01-01CIC0203/011
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 8

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.

Conditions

Evidence of Liver Transplantation

Keywords

Immunosuppression; Liver transplantation; Acute graft rejection; Treatment combination

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil

  between Day 1 and Week 48

Study Arms (2)

MMF+FK

EXPERIMENTAL

Low doses of tacrolimus in association with mycophenolate mofetil

Drug: Mycophenolate mofetil; Drug: Tacrolimus

FK

ACTIVE COMPARATOR

Full recommended doses of tacrolimus

Drug: Tacrolimus

Interventions

Mycophenolate mofetil DRUG

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.

Also known as: MMF, CELLCEPT

MMF+FK

Tacrolimus DRUG

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.

Also known as: FK, PROGRAF

FK; MMF+FK

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

Sponsors & Collaborators

• Rennes University Hospital: lead
• Ministry of Health, France: collaborator

Study Sites (8)

Service de Chirurgie Digestive - Hôpital de la Côte de Nacre

Caen, 14033, France

Location

Service d'Hépatogastroentérologie - Hôpital Beaujon

Clichy, 92110, France

Location

Service d'Hépatogastroentérologie - Hôpital Henri Mondor

Créteil, 94010, France

Location

Chirurgie Générale et Digestive - Hôpital de La Croix Rousse

Lyon, 69317, France

Location

Service d'Hépaogastroentérologie - Hôpital Saint Eloi

Montpellier, France

Location

Service de Chirurgie Générale - Hôpital Cochin

Paris, 75679, France

Location

Département de Chirurgie Viscérale - Hôpital Pontchaillou

Rennes, 35033, France

Location

Centre Hépato-biliaire - Hôpital Paul Brousse

Villejuif, France

Location

Related Publications (2)

• Jain AB, Hamad I, Rakela J, Dodson F, Kramer D, Demetris J, McMichael J, Starzl TE, Fung JJ. A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients: an interim report. Transplantation. 1998 Nov 27;66(10):1395-8. doi: 10.1097/00007890-199811270-00024.

  PMID: 9846530 BACKGROUND

• Klupp J, Glanemann M, Bechstein WO, Platz KP, Langrehr JM, Keck H, Settmacher U, Radtke C, Neuhaus R, Neuhaus P. Mycophenolate mofetil in combination with tacrolimus versus Neoral after liver transplantation. Transplant Proc. 1999 Feb-Mar;31(1-2):1113-4. doi: 10.1016/s0041-1345(98)01925-3. No abstract available.

  PMID: 10083497 BACKGROUND

MeSH Terms

Interventions

Mycophenolic Acid; Tacrolimus

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Karim Boudjema, MD, PhD

  CHU Rennes

  STUDY DIRECTOR

• Eric Bellissant, MD, PhD

  CHU Rennes

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 9, 2005
• Study Start: May 1, 2003
• Primary Completion: December 1, 2008
• Study Completion: May 1, 2009
• Last Updated: July 4, 2012

Record last verified: 2012-07

Locations

FR (8)