Treatment of Recurrent Hepatitis C After Liver Transplantation

Phase 3

Completed

• Conditions: Liver Transplantation; Hepatitis C
• Interventions: Drug: Ribavirin; Drug: Placebo

• Registration Number: NCT00151580
• Lead Sponsor: Rennes University Hospital

Brief Summary

In France, 50% of the hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation. This recurrence usually causes chronic liver disease, in 50 to 80% of the patients. The interest of a long-term treatment with ribavirin alone after transplantation has not been clearly demonstrated. The objective of our study is to evaluate the efficacy of ribavirin as a maintenance treatment after a one year interferon-α / ribavirin therapy on hepatitis C recurrence in the transplanted liver.

Detailed Description

Several therapeutic patterns have been described for the treatment of hepatitis C post-transplantation recurrence. A combination treatment associating interferon-α and ribavirin has shown some efficacy, but this efficacy has not been assessed yet in a placebo-controlled double-blind clinical trial. In our study, all included transplanted patients will be treated during 1 year with interferon-α and ribavirin. At the end of this period, they will be randomized to receive a maintenance treatment with ribavirin or a placebo for 1 additional year. Efficacy will be assessed on virological response after 30 months of treatment.

Study Timeline

• Study Start: 2002-02
• Study First Submitted: 2005-09-08
• Study First Submitted QC: 2005-09-08
• Study First Posted: 2005-09-09
• Study Completion: 2006-07
• Status Verified: 2007-11
• Last Update Submitted: 2012-05-18
• Last Update Posted: 2012-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• First liver transplantation or retransplantation in the month after initial transplantation
• Patients aged over 18 years
• Post-hepatitis C cirrhosis
• Equilibrated immunosuppressive treatment
• Positive PCR for hepatitis C virus
• Liver biopsy between 6 months and 5 years after the transplantation with a fibrosis Metavir score at least F1
• Hemoglobin ≥ 10 g/dl
• Platelet count ≥ 50.000/mm3
• Normal TSH value
• Serum creatinine < 200µmol/l
• Informed written consent

Exclusion Criteria

• Chronic rejection
• Acute rejection at inclusion
• Multi-visceral transplantation
• Renal or cardiac failure, severe sepsis
• Uncontrolled diabetes
• Positive serology for hepatitis B or HIV at inclusion
• EBV virus replication at inclusion
• Hepatocellular carcinoma at inclusion
• Cirrhosis with a fibrosis Metavir score F4 at inclusion
• Inclusion in another clinical trial less than one month ago
• Pregnancy
• Contra-indication to ribavirin or interferon
• History of or current psychiatric troubles
• Thyroid disease uncontrolled by treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Ribavirin	Ribavirin maintenance treatment
2	Placebo	-

Primary Outcome Measures

Name	Time	Method
Negative viral PCR	30 months

Secondary Outcome Measures

Name	Time	Method
Histological improvement	30 months
Biological hepatic markers	30 months
Quality of life	30 months
Intensity, severity and delay to acute transplant rejection, histologically proven	30 months
Incidence of death or graft loss	30 months
Number of patients stopping the treatment and causes	30 months
Incidence of adverse events classically related to treatment	30 months
Incidence of adverse events possibly related to treatment	30 months

Trial Locations

Locations (16)

Service de Chirurgie Générale et Digestive - Hôpital Cochin; 🇫🇷 Paris, France

Service de Chirurgie Digestive - Groupe Hospitalier Pellerin-Tripode; 🇫🇷 Bordeaux, France

Service d'Hépatologie - Hôpital Jean Minjoz; 🇫🇷 Besancon, France

Service d'Hépatogastroentérologie - Hôpital Beaujon; 🇫🇷 Clichy, France

Chirurgie Générale - Hôpital de la Conception; 🇫🇷 Marseille, France

Médecine Digestive - Hôtel Dieu; 🇫🇷 Lyon, France

Service d'Hépatologie et Gastroentérologie - Hôpital Henri Mondor; 🇫🇷 Créteil, France

Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez; 🇫🇷 Lille, France

Service de Chirurgie Générale - Hôpital Edouard Herriot; 🇫🇷 Lyon, France

Service d'Hépaogastroentérologie - Hôpital Saint Eloi; 🇫🇷 Montpellier, France

Chirurgie Viscérale et Digestive -Hôpital de l'Archet; 🇫🇷 Nice, France

Service Hépato-gastroentérologie - Hôpital Saint Antoine; 🇫🇷 Paris, France

Département de Chirurgie Viscérale- Hôpital Pontchaillou; 🇫🇷 Rennes, France

Hôpital de Rangueil; 🇫🇷 Toulouse, France

Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre; 🇫🇷 Strasbourg, France

Centre Hépato-biliaire - Hôpital Paul Brousse; 🇫🇷 Villejuif, France