Treatment of Recurrent Hepatitis C After Liver Transplantation

NCT ID: NCT00151580

Last Updated: 2012-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2006-07-31

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.

Conditions

Liver Transplantation; Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

1

Ribavirin maintenance treatment

Group Type: EXPERIMENTAL

Ribavirin

Intervention Type: DRUG

18 months of oral ribavirin maintenance treatment

2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

18 months oral placebo treatment

Interventions

Ribavirin

18 months of oral ribavirin maintenance treatment

Intervention Type: DRUG

Placebo

18 months oral placebo treatment

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: lead

Principal Investigators

Karim Boudjema, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHU Rennes

Yvon Calmus, MD

Role: PRINCIPAL_INVESTIGATOR

AP-HP Hôpital Cochin

Locations

Service d'Hépatologie - Hôpital Jean Minjoz

Besançon, , France

Service de Chirurgie Digestive - Groupe Hospitalier Pellerin-Tripode

Bordeaux, , France

Service d'Hépatogastroentérologie - Hôpital Beaujon

Clichy, , France

Service d'Hépatologie et Gastroentérologie - Hôpital Henri Mondor

Créteil, , France

Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez

Lille, , France

Médecine Digestive - Hôtel Dieu

Lyon, , France

Service de Chirurgie Générale - Hôpital Edouard Herriot

Lyon, , France

Chirurgie Générale - Hôpital de la Conception

Marseille, , 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

Service de Chirurgie Générale et Digestive - Hôpital Cochin

Paris, , France

Département de Chirurgie Viscérale- Hôpital Pontchaillou

Rennes, , France

Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre

Strasbourg, , France

Hôpital de Rangueil

Toulouse, , France

Centre Hépato-biliaire - Hôpital Paul Brousse

Villejuif, , France

Countries

France

References

Cattral MS, Hemming AW, Wanless IR, Al Ashgar H, Krajden M, Lilly L, Greig PD, Levy GA. Outcome of long-term ribavirin therapy for recurrent hepatitis C after liver transplantation. Transplantation. 1999 May 15;67(9):1277-80. doi: 10.1097/00007890-199905150-00014.

Reference Type: BACKGROUND

PMID: 10342322 (View on PubMed)

Berenguer M, Prieto M, Cordoba J, Rayon JM, Carrasco D, Olaso V, San-Juan F, Gobernado M, Mir J, Berenguer J. Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection. J Hepatol. 1998 May;28(5):756-63. doi: 10.1016/s0168-8278(98)80224-9.

Reference Type: BACKGROUND

PMID: 9625309 (View on PubMed)

Other Identifiers

PHRC/00-02

Identifier Type: -

Identifier Source: secondary_id

CIC0203/049

Identifier Type: -

Identifier Source: secondary_id

AFSSAPS 010588

Identifier Type: -

Identifier Source: org_study_id