Interest of Ribavirin in the Maintenance Treatment of Liver Fibrosis Using Low Dose Pegylated Interferon alpha2b in Patients With Chronic Hepatitis C Non Responders to Previous Antiviral Therapy.

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by French National Agency for Research on AIDS and Viral Hepatitis.
Recruitment status was  Recruiting
Rennes University Hospital
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis Identifier:
First received: May 9, 2006
Last updated: March 18, 2008
Last verified: March 2008

Patients with chronic hepatitis C who did not respond to previous antiviral treatment develop liver fibrosis leading to cirrhosis. Maintenance low dose pegylated interferon therapy of fibrosis is currently under investigation in large multicenter trials. The aim of our study is to assess if peginterferon alpha2b plus ribavirin is more efficient than peginterferon alpha2b alone. 454 patients will be randomized between the 2 arms and the efficacy will be assessed, after 3 years of treatment, on Metavir liver fibrosis score improvement.

Condition Intervention Phase
Hepatitis C, Chronic
Liver Fibrosis
Drug: Peginterferon alpha-2b + ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled Multicenter Study Evaluating the Interest of a Long-Term (3 Years) Treatment With Peginterferon Alfa-2b and Ribavirin on Liver Fibrosis in Non-Responder Chronic Hepatitis C Patients.

Resource links provided by NLM:

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • Rate of patients with at least a one point improvement in Metavir fibrosis score between the inclusion and the end-of-study liver biopsies.

Secondary Outcome Measures:
  • Distribution of the Metavir scoring on the end-of-study biopsy
  • Distribution of the Chevallier fibrosis score
  • Evolution of the area of fibrosis between the inclusion and the end-of -study biopsies
  • Fibrosis serum markers
  • Liver elasticity before and after treatment
  • Safety of treatment and quality of life
  • Frequency of occurrence of hepatic complications and/or liver transplantations
  • Evolution of the hepatitis C viral load
  • Rate of patients with loss of detectable hepatitis C virus RNA

Estimated Enrollment: 454
Study Start Date: May 2006
Detailed Description:

Up to 45% of patients with chronic hepatitis C do not respond to pegylated interferon/ribavirin combination therapy. These patients are prone to develop liver fibrosis leading to cirrhosis and its complications. Interferon has proven to be efficient in liver fibrosis treatment even in case of virological non response. Maintenance low dose pegylated interferon therapy is currently under investigation in large multicenter trials. The aim of our study is to assess wether peginterferon alpha 2 b (0.5 µg/kg/week) plus ribavirin (800-1200 mg according to body weight) is more efficient than peginterferon alpha 2 b alone in a long term 3 years treatment of liver fibrosis. 454 patients, non responders (VHC RNA positive after 24 weeks of treatment or absence of ≥ 2 log HCV RNA drop after 12 weeks of treatment) to a previous peginterferon/ribavirin antiviral treatment will be randomized between the 2 arms, with a double-blind masking of ribavirin. The efficacy will be assessed on Metavir liver fibrosis score improvement between pre and post therapeutic liver biopsy.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adults over 18
  • With a hepatitis C virus infection (HCV RNA and anti-HCV antibodies in serum)
  • Not responders to a previous antiviral treatment using the interferon plus ribavirin combination
  • With a wash-out of treatment for at least 6 months
  • With an active chronic hepatitis C and a Metavir fibrosis score ≥ 2
  • Serum ALT levels > upper limit of the laboratory on two occasions within 6 months before inclusion
  • Accepting to undergo a liver biopsy at the end of the study
  • Negative pregnancy test for women
  • With a social security cover
  • Written informed consent

Exclusion Criteria:

  • History of hepatic complications
  • History of transplantation
  • History of severe seizures
  • History of severe psychiatric disorders
  • Drug addiction within the last 12 months
  • Associated condition susceptible to be responsible for liver fibrosis
  • Hepatocellular carcinoma
  • Cardiovascular disease unstable under treatment
  • Uncontrolled diabetes
  • Retinopathy
  • Thyroid disease unstable under treatment
  • Epilepsy and/or central nervous system functional disorders
  • Autoimmune disease
  • Regular alcohol consumption
  • Pregnancy, breast-feeding or absence of contraception
  • Haemoglobin <12 g/dl
  • platelets <50000/mm3
  • Neutrophils < 1200/ mm3
  • Severe hepatocellular failure (prothrombin index lower than 60%)
  • Renal failure (creatinine clearance lower than 50 mL/Mn)
  • Associated immunosuppressive drugs, corticosteroids, antiviral drugs (other than study ones)
  • Treatment with drugs likely to have an effect on fibrosis
  • Anticonvulsants
  • Inability to tolerate interferon
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Please refer to this study by its identifier: NCT00323804

Contact: Dominique Guyader, MD 33-2-9928-4297
Contact: Eric Bellissant, MD, PhD 33-2-9928-9200

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Service d' Hépatogastroentérologie - Hôpital Jean Verdier Recruiting
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Cabinet Médical Recruiting
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Sub-Investigator: Florence Tanné, MD         
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Service d'Hépatogastroentérologie - Hotel Dieu Recruiting
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Sub-Investigator: Karine Randl, MD         
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Sub-Investigator: Nathalie Boyer, MD         
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Corbeil-Essonnes, France, 91100
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Principal Investigator: Jacques Denis, MD         
Sub-Investigator: Bénédicte Lambaré, MD         
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Principal Investigator: Patrick Hillon, MD         
Sub-Investigator: Anne Minello, MD         
Service d'Hépatogastroentérologie - CH La Roche sur Yon Recruiting
La Roche sur Yon, France, 85925
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Principal Investigator: Matthieu Schnée, MD         
Sub-Investigator: Jean-Pierre Lafargue, MD         
Service des Maladies du Foie et de l'appareil Digestif - Hôpital de Bicêtre Recruiting
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Principal Investigator: Rita Bou Farah, MD         
Sub-Investigator: Catherine Buffet, MD         
Département d'Hépatogastroentérologie - CH Le Mans Recruiting
Le Mans, France, 72037
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Sub-Investigator: Alain Blanchi, MD         
Service d'Hépatogastroentérologie - CHRU - Hôpital Claude Huriez Recruiting
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Principal Investigator: Philippe Mathurin, MD         
Sub-Investigator: Valérie Canva, MD         
Unité de Médecine Interne A - Hôpital Dupuytren Recruiting
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Sub-Investigator: Marilyne Debette Gratien, MD         
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Lyon, France, 69288
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Service d'Hépatogastroentérologie - Hôpital Saint Joseph Recruiting
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Service d'Hépatogastroentérologie - CH Montauban Recruiting
Montauban, France, 82000
Contact: Jean-Louis Payen, MD    33-5-6392-8119   
Principal Investigator: Jean-Louis Payen, MD         
Service d'Hépatogastroentérologie - CH Montélimar Recruiting
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Montpellier, France, 34295
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Sub-Investigator: Georges Pageaud, MD         
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Principal Investigator: Jérôme Gournay, MD         
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Pessac, France, 33604
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Principal Investigator: Victor De Ledinghen, MD         
Sub-Investigator: Juliette Foucher, MD         
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Rennes, France, 35033
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Sub-Investigator: Yves Deugnier, MD         
Service d'Hépatogastroentérologie - CHU Rouen Recruiting
Rouen, France, 76031
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Saint Dizier, France, 52115
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Strasbourg, France, 67000
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Sub-Investigator: François Habersezter, MD         
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Toulouse, France, 31059
Contact: Jean-Pierre Vinel, MD    33-5-6177-2114   
Contact: Laurent Alric, MD   
Principal Investigator: Jean-Pierre Vinel, MD         
Sub-Investigator: Laurent Alric, MD         
Sub-Investigator: Sophie Metivier, MD         
Service d'Hépatogastroentérologie - Hôpital Trousseau Recruiting
Tours, France, 37044
Contact: Louis d'Alteroche, MD    33-2-4747-5965      
Principal Investigator: Louis d'Alteroche, MD         
Sub-Investigator: Yannick Bacq, MD         
Service d'Hépatogastroentérologie - Hôpital Brabois Recruiting
Vandoeuvre les Nancy, France, 54500
Contact: Jean-Pierre Bronowicki, MD    33-3-8315-3359   
Principal Investigator: Jean-Pierre Bronowicki, MD         
Sub-Investigator: Laurence Chone, MD         
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Rennes University Hospital
Principal Investigator: Dominique Guyader, MD CHU Rennes
Study Chair: Eric Bellissant, MD, PhD CHU Rennes
  More Information

No publications provided

Responsible Party: Nadia Squalli/regulatory affairs, ANRS Identifier: NCT00323804     History of Changes
Other Study ID Numbers: ANRS HC15 NRfi, AFSSAPS 060246-34, CIC0203/020, EUDRACT 2005-002937-11
Study First Received: May 9, 2006
Last Updated: March 18, 2008
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
Maintenance therapy
Non-responder patients
Ribavirin/peginterferon combination therapy
Hepatitis C, Chronic

Additional relevant MeSH terms:
Hepatitis C, Chronic
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Peginterferon alfa-2b
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs processed this record on August 27, 2014