Clinical trial NCT00151580: Treatment of Recurrent Hepatitis C After Liver Transplantation
Official title: Comparison of Maintenance Treatment by Ribavirin to a Placebo, After an Initial One-year Treatment With Pegylated Interferon-α2a - Ribavirin Association in Hepatitis C Viral Recurrence After Liver Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Transplantation
Hepatitis C
Keywords: Hepatitis C
Viral recurrence
Ribavirin / Interferon
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: ANRS, Emerging Infectious Diseases
First posted: 2005-09-09
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Negative viral PCR
timeFrame: 30 months
Secondary outcomes:
measure: Histological improvement
timeFrame: 30 months
measure: Biological hepatic markers
timeFrame: 30 months
measure: Quality of life
timeFrame: 30 months
measure: Intensity, severity and delay to acute transplant rejection, histologically proven
timeFrame: 30 months
measure: Incidence of death or graft loss
timeFrame: 30 months
measure: Number of patients stopping the treatment and causes
timeFrame: 30 months
measure: Incidence of adverse events classically related to treatment
timeFrame: 30 months
measure: Incidence of adverse events possibly related to treatment
timeFrame: 30 months
Other outcomes:
Locations:
city: Besancon
country: France
facility: Service d'Hépatologie - Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Service de Chirurgie Digestive - Groupe Hospitalier Pellerin-Tripode
city: Clichy
country: France
facility: Service d'Hépatogastroentérologie - Hôpital Beaujon
city: Créteil
country: France
facility: Service d'Hépatologie et Gastroentérologie - Hôpital Henri Mondor
city: Lille
country: France
facility: Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez
city: Lyon
country: France
facility: Médecine Digestive - Hôtel Dieu
city: Lyon
country: France
facility: Service de Chirurgie Générale - Hôpital Edouard Herriot
city: Marseille
country: France
facility: Chirurgie Générale - Hôpital de la Conception
city: Montpellier
country: France
facility: Service d'Hépaogastroentérologie - Hôpital Saint Eloi
city: Nice
country: France
facility: Chirurgie Viscérale et Digestive -Hôpital de l'Archet
city: Paris
country: France
facility: Service Hépato-gastroentérologie - Hôpital Saint Antoine
city: Paris
country: France
facility: Service de Chirurgie Générale et Digestive - Hôpital Cochin
city: Rennes
country: France
facility: Département de Chirurgie Viscérale- Hôpital Pontchaillou
city: Strasbourg
country: France
facility: Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre
city: Toulouse
country: France
facility: Hôpital de Rangueil
city: Villejuif
country: France
facility: Centre Hépato-biliaire - Hôpital Paul Brousse
Study officials:
affiliation: CHU Rennes
name: Karim Boudjema, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HP Hôpital Cochin
name: Yvon Calmus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.