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

Liver Transplantation Clinical Trial

— BEFIRTH  

Official title:

Evaluation of the Benefit of Antithymocyte Induction Therapy on Hepatic Fibrosis in de Novo Hepatitis C Virus Liver Transplant Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00538265
• Other study ID #: 0404003
• Status: Completed
• Phase: Phase 4
• First received: October 1, 2007
• Last updated: February 2, 2011
• Start date: May 2005
• Est. completion date: January 2011

Study information

• Verified date: February 2011
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

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
• 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)
• 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.

Locations

Country	Name	City	State
France	Hopital Pellegrin Tripode	Bordeaux
France	La CONCEPTION hospital	Marseille
France	Hopital Saint-Eloi	Montpellier
France	Hopital de L'Archet	Nice
France	Hôpital Cochin	Paris
France	Hôpital Pontchaillou	Rennes
France	University Hospital	Toulouse
France	Hopital Paul Brousse	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year		1 year	No
Secondary	• Ishak's degree of activity		1 year	No
Secondary	Ishak's degree of fibrosis		2 years	No