Treatment of Recurrent Hepatitis C After Liver Transplantation

Hepatitis C Clinical Trial

— TRANSPEG  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00151580
• Other study ID #: AFSSAPS 010588
• Secondary ID: PHRC/00-02CIC020
• Status: Completed
• Phase: Phase 3
• First received: September 8, 2005
• Last updated: May 18, 2012
• Start date: February 2002
• Est. completion date: July 2006

Study information

• Verified date: November 2007
• Source: Rennes University Hospital
• 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

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Liver Transplantation

Intervention

Drug:
• Ribavirin
18 months of oral ribavirin maintenance treatment
• Placebo
18 months oral placebo treatment

Locations

Country	Name	City	State
France	Service d'Hépatologie - Hôpital Jean Minjoz	Besancon
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 de Chirurgie Générale et Digestive - Hôpital Cochin	Paris
France	Service Hépato-gastroentérologie - Hôpital Saint Antoine	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

Sponsors (3)

Lead Sponsor	Collaborator
Rennes University Hospital	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS), Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (2)

Berenguer M, Prieto M, Córdoba J, Rayón 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Negative viral PCR		30 months
Secondary	Histological improvement		30 months
Secondary	Biological hepatic markers		30 months
Secondary	Quality of life		30 months
Secondary	Intensity, severity and delay to acute transplant rejection, histologically proven		30 months
Secondary	Incidence of death or graft loss		30 months
Secondary	Number of patients stopping the treatment and causes		30 months
Secondary	Incidence of adverse events classically related to treatment		30 months
Secondary	Incidence of adverse events possibly related to treatment		30 months