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Benefit of Immunoprophylaxis on Fibrosis to Reduce Viral Load After Liver Transplantation (BEFIRTH)

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT00538265
First received: October 1, 2007
Last updated: February 2, 2011
Last verified: February 2011
History of Changes
  Purpose

An open-label randomized multicenter clinical study comparing three regimes of immunosuppression : (A) tacrolimus and steroids, (B) antithymocyte induction therapy and full dose of tacrolimus, (C) antithymocyte induction therapy with mycophenolate mofetil and a reduced dose of tacrolimus.


Condition Intervention Phase
Liver Transplantation
 Drug: tacrolimus
Drug: tacrolimus, ATG
Drug: ATG+mycophénolate mofétil+tacrolimus
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Benefit of Antithymocyte Induction Therapy on Hepatic Fibrosis in de Novo Hepatitis C Virus Liver Transplant Patients.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • • Ishak's degree of activity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Ishak's degree of fibrosis [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: May 2005
Study Completion Date: January 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
tacrolimus + steroids
 Drug: tacrolimus
Tacrolimus started at 0.50 mg/kg b.i.d. starting at D0, by nasogastric tube and then 1 to 2 hours before meals. The dose of tacrolimus will be adjusted as soon as possible to obtain trough concentrations of the product between 10 and 20 µg/L between D0 and 6 months and then between 8 and 15 µg/L after 6 months
Other Name: PROGRAF
Experimental: B
ATG+ tacrolimus without steroids in maintenance therapy
 Drug: tacrolimus, ATG

immunoprophylaxis allowing sparing of steroids in maintenance therapy combining induction therapy with 3 injections of antithymocyte globulins (ATG) (1.5 mg/kg/d at D0, D2 and D4) and tacrolimus at usual dosage.

In this group of patients, the first injection of ATG will be infused over a period of at least 6 hours and will be started as soon as vascular anastomosis has been completed. It will be preceded by an injection of 3 mg/kg/d methylprednisolone. The second injection of ATG at D2, post transplantation will also be infused over 6 hours and will be preceded by an injection of 1 mg/kg methylprednisolone, and then subsequently steroids will be excluded from the treatment. The third and last injection at D4 post transplantation will be administered over a 6-hour period but will not be preceded by steroids.

In this study arm, tacrolimus will be administered as in arm (A)

Other Name: Thymoglobuline
Experimental: C
ATG+ Mycophenolate Mofetil + tacrolimus a reduced dosage without steroids in maintenance therapy
 Drug: ATG+mycophénolate mofétil+tacrolimus

immunoprophylaxis allowing sparing of steroids in maintenance therapy combined with mycophenolate mofetil, at an initial dosage of 2 grams a day, and then adjusted to safety and tolerability in such a way so as to maintain PMN ≥ 750/mm3, and platelet counts ≥ 30000/mm3.

In this study arm, the patients will receive the same doses of ATG and steroids (and according to the same methods) as in arm B. Tacrolimus started at 0.05 mg/kg b.i.d. starting at D0 by nasogastric tube and then 1 to 2 hours before meals. In this study arm, the tacrolimus dose will be reduced: targeted trough concentrations will be between 7 and 12 µg/L between D0 and 6 months and then between 3 et 7 µg/L after 6 months.

Other Name: Mycophénolate mofétil = Cellcept

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients who received a first liver transplantation,
  • presenting with a qualitative or quantitative PCR positive for hepatitis C virus at time of transplantation, whatever the transaminase activity,
  • Women of childbearing potential with a negative pregnancy test,
  • Male or female patients who agree to use an effective method of contraception,
  • patients who signed a written informed consent form to participate in the study,
  • patients who are compliant and likely to follow the visits specified by the study protocol

Exclusion Criteria:

  • • Preoperative serious renal impairment (serum creatinine levels > 200 µmol/l),

    • repeat transplantation,
    • multiple organ transplantation,
    • transplantation performed with an organ transplant obtained from a living donor or a reduced or shared organ grafts,
    • serious concomitant disorder,
    • positive serology for HBs antigen or HIV positive at time of enrollment,
    • previous history of nonhepatic cancer (except for localized skin cancer),
    • presence of a hepatocellular carcinoma, for which the primary lesion exceeds 5 cm or is complicated by portal thrombosis or metastatic disease,
    • an investigational product or therapy administered less than one month before entry into the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00538265

Locations
France
Hopital Pellegrin Tripode
Bordeaux, France, 33076
La CONCEPTION hospital
Marseille, France, 13385
Hopital Saint-Eloi
Montpellier, France, 34295
Hopital de L'Archet
Nice, France, 06200
Hôpital Cochin
Paris, France, 75000
Hôpital Pontchaillou
Rennes, France, 35
University Hospital
Toulouse, France, 31500
Hopital Paul Brousse
Villejuif, France, 94804
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Rostaing Lionel, PhD University Hospital, Toulouse
Principal Investigator: Calmus Yvon, PhD UHCochin, Paris
  More Information

No publications provided

Responsible Party: LLAU ME, University Hospital Toulouse
ClinicalTrials.gov Identifier: NCT00538265     History of Changes
Other Study ID Numbers: 0404003
Study First Received: October 1, 2007
Last Updated: February 2, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
liver transplantation, hepatitis C virus, immunoprophylaxis

Additional relevant MeSH terms:
Fibrosis
Hepatitis C
Pathologic Processes
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Mycophenolate mofetil
 Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2013