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

Primary Purpose

Liver Transplantation

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
tacrolimus
tacrolimus, ATG
ATG+mycophénolate mofétil+tacrolimus
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Transplantation focused on measuring liver transplantation, hepatitis C virus, immunoprophylaxis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hopital Pellegrin Tripode
  • La CONCEPTION hospital
  • Hopital Saint-Eloi
  • Hopital de L'Archet
  • Hôpital Cochin
  • Hôpital Pontchaillou
  • University Hospital
  • Hopital Paul Brousse

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

A

B

C

Arm Description

tacrolimus + steroids

ATG+ tacrolimus without steroids in maintenance therapy

ATG+ Mycophenolate Mofetil + tacrolimus a reduced dosage without steroids in maintenance therapy

Outcomes

Primary Outcome Measures

The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year

Secondary Outcome Measures

• Ishak's degree of activity
Ishak's degree of fibrosis

Full Information

First Posted
October 1, 2007
Last Updated
February 2, 2011
Sponsor
University Hospital, Toulouse
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1. Study Identification

Unique Protocol Identification Number
NCT00538265
Brief Title
Benefit of Immunoprophylaxis on Fibrosis to Reduce Viral Load After Liver Transplantation
Acronym
BEFIRTH
Official Title
Evaluation of the Benefit of Antithymocyte Induction Therapy on Hepatic Fibrosis in de Novo Hepatitis C Virus Liver Transplant Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University Hospital, Toulouse

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Transplantation
Keywords
liver transplantation, hepatitis C virus, immunoprophylaxis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Description
tacrolimus + steroids
Arm Title
B
Arm Type
Experimental
Arm Description
ATG+ tacrolimus without steroids in maintenance therapy
Arm Title
C
Arm Type
Experimental
Arm Description
ATG+ Mycophenolate Mofetil + tacrolimus a reduced dosage without steroids in maintenance therapy
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Other Intervention Name(s)
PROGRAF
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
tacrolimus, ATG
Other Intervention Name(s)
Thymoglobuline
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
ATG+mycophénolate mofétil+tacrolimus
Other Intervention Name(s)
Mycophénolate mofétil = Cellcept
Intervention Description
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.
Primary Outcome Measure Information:
Title
The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year
Time Frame
1 year
Secondary Outcome Measure Information:
Title
• Ishak's degree of activity
Time Frame
1 year
Title
Ishak's degree of fibrosis
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rostaing Lionel, PhD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Calmus Yvon, PhD
Organizational Affiliation
UHCochin, Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Pellegrin Tripode
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
La CONCEPTION hospital
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Hopital Saint-Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital de L'Archet
City
Nice
ZIP/Postal Code
06200
Country
France
Facility Name
Hôpital Cochin
City
Paris
ZIP/Postal Code
75000
Country
France
Facility Name
Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35
Country
France
Facility Name
University Hospital
City
Toulouse
ZIP/Postal Code
31500
Country
France
Facility Name
Hopital Paul Brousse
City
Villejuif
ZIP/Postal Code
94804
Country
France

12. IPD Sharing Statement

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

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