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
Sponsor:
Collaborators:
Schering-Plough
Rennes University Hospital
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00323804
First received: May 9, 2006
Last updated: March 18, 2008
Last verified: March 2008
  Purpose

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.

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00323804

Contacts
Contact: Dominique Guyader, MD 33-2-9928-4297 Dominique.Guyader@univ-rennes1.fr
Contact: Eric Bellissant, MD, PhD 33-2-9928-9200 eric.bellissant@chu-rennes.fr

Locations
France
Service d'Hépatogastroentérologie et d'endoscopie digestive - CH du Pays d'Aix Recruiting
Aix en Provence, France, 13616
Contact: Claire Wartelle, MD    33-4-4233-5064      
Principal Investigator: Claire Wartelle, MD         
Sub-Investigator: Magali Picon-Coste, MD         
Service d'Hépatogastroentérologie - Hôpital Nord Recruiting
Amiens, France, 80054
Contact: Dominique Capron, MD    33-3-2266-8207    capron.dominique@chu-amiens.fr   
Principal Investigator: Dominique Capron, MD         
Sub-Investigator: Eric Nguyen-Khac, MD         
Service d'Hépatologie - Gastroentérologie - Cancérologie digestive - CHU Angers Recruiting
Angers, France, 49100
Contact: Paul Calès, MD    33-2-4135-5522    Paul.Cales@univ-angers.fr   
Principal Investigator: Paul Calès, MD         
Sub-Investigator: Isabelle Hubert-Fouchard, MD         
Service d'Hépatogastroentérologie - CH Victor Dupouy Recruiting
Argenteuil, France, 95100
Contact: Philippe Renard, MD    33-1-3423-1674    philippe.renard@ch-argenteuil.fr   
Principal Investigator: Philippe Renard, MD         
Sub-Investigator: Daniel Salaun, MD         
Service d'Hépatogastroentérologie - Hôpital Jean Minjoz Recruiting
Besançon, France, 25000
Contact: Jean-Philippe Miguet, MD    33-3-8166-8421    jean-philippe.miguet@ufc-chu.univ-fcomt   
Principal Investigator: Jean-Philippe Miguet, MD         
Sub-Investigator: Claire Valemmens, MD         
Service d'Hépatogastroentérologie - Hôpital Avicenne Recruiting
Bobigny, France, 93009
Contact: Dominique Roulot, MD    33-1-4895-5373    dominique.roulot@avc.aphp.fr   
Principal Investigator: Dominique Roulot, MD         
Service d' Hépatogastroentérologie - Hôpital Jean Verdier Recruiting
Bondy, France, 93143
Contact: Michel Beaugrand, MD    33-1-4802-6280    michel.beaugrand@jvr.aphp.fr   
Principal Investigator: Michel Beaugrand, MD         
Sub-Investigator: Véronique Grando, MD         
Cabinet Médical Recruiting
Bourgoin-Jallieu, France, 38300
Contact: Thierry Fontanges, MD    33-4-7428-0844    fontanges@aol.com   
Principal Investigator: Thierry Fontanges, MD         
Service d'Hépatogastroentérologie - Hôpital de la Cavale Blanche Recruiting
Brest, France, 29200
Contact: Jean-Baptiste Nousbaum, MD    33-2-9834-7148    jean-baptiste.nousbaum@chu-brest.fr   
Principal Investigator: Jean-Baptiste Nousbaum, MD         
Sub-Investigator: Florence Tanné, MD         
Service d'Hépatologie - Gastroentérologie - Nutrition -Hôpital de la Côte de Nacre Recruiting
Caen, France, 14000
Contact: Thong Dao, MD    33-2-3106-4544    dao-t@chu-caen.fr   
Principal Investigator: Thong Dao, MD         
Sub-Investigator: Samouh Elfadel, MD         
Service d'Hépatogastroentérologie - CH de Chateauroux Recruiting
Chateauroux, France, 36000
Contact: Thierry Sapey, MD    33-2-5429-6002    thierrysapey@hotmail.com   
Principal Investigator: Thierry Sapey, MD         
Sub-Investigator: Denis Kabissa Imed, MD         
Service d'Hépatogastroentérologie - Hotel Dieu Recruiting
Clermont-Ferrand, France, 63058
Contact: Armand Abergel, MD    33-4-7375-0504    aabergel@chu-clermontferrand.fr   
Principal Investigator: Armand Abergel, MD         
Sub-Investigator: Karine Randl, MD         
Service d'Hépatogastroentérologie - Hôpital Beaujon Recruiting
Clichy, France, 92110
Contact: Patrick Marcellin, MD    33-1-4087-5522    patrick.marcellin@bjn.aphp.fr   
Principal Investigator: Patrick Marcellin, MD         
Sub-Investigator: Nathalie Boyer, MD         
Service d'Hépatogastroentérologie - CH Sud Francilien Recruiting
Corbeil-Essonnes, France, 91100
Contact: Jacques Denis, MD    33-1-6087-7834    jacques.denis@ch-sud-francilien.fr   
Principal Investigator: Jacques Denis, MD         
Sub-Investigator: Bénédicte Lambaré, MD         
Service d'Hépatogastroentérologie - Hôpital du Bocage Recruiting
Dijon, France, 21079
Contact: Patrick Hillon, MD    33-3-8029-3750    patrick.hillon@chu-dijon.fr   
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
Contact: Matthieu Schnée, MD    33-2-5144-6168    matthieu.schnée@chd-vendee.fr   
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
Le Kremlin-Bicetre, France, 94275
Contact: Rita Bou Farah, MD    33-1-4521-3724      
Principal Investigator: Rita Bou Farah, MD         
Sub-Investigator: Catherine Buffet, MD         
Département d'Hépatogastroentérologie - CH Le Mans Recruiting
Le Mans, France, 72037
Contact: Christophe Pilette, MD    33-2-4343-2752    cpilette@ch-lemans.fr   
Principal Investigator: Christophe Pilette, MD         
Sub-Investigator: Alain Blanchi, MD         
Service d'Hépatogastroentérologie - CHRU - Hôpital Claude Huriez Recruiting
Lille, France, 59000
Contact: Philippe Mathurin, MD    33-3-2044-5343    p-mathurin@chru-lille.fr   
Principal Investigator: Philippe Mathurin, MD         
Sub-Investigator: Valérie Canva, MD         
Unité de Médecine Interne A - Hôpital Dupuytren Recruiting
Limoges, France, 87042
Contact: Véronique Loustaud-Ratti, MD    33-5-5505-6684    veronique.loustaud-ratti@unilim.fr   
Principal Investigator: Véronique Loustaud-Ratti, MD         
Sub-Investigator: Marilyne Debette Gratien, MD         
Service d'Hépatogastroentérologie - Hotel Dieu Recruiting
Lyon, France, 69288
Contact: Christian Trépo, MD    33-4-7241-3089    christian.trépo@chu-lyon.fr   
Principal Investigator: Christian Trépo, MD         
Sub-Investigator: Fabien Zoulim, MD         
Service d'Hépatogastroentérologie - Hôpital Saint Joseph Recruiting
Marseille, France, 13008
Contact: Marc Bourlière, MD    33-4-9180-6608    mbourliere@hopital-saint-joseph.fr   
Principal Investigator: Marc Bourlière, MD         
Sub-Investigator: Valérie Oules, MD         
Service d'Hépatogastroentérologie - CH Montauban Recruiting
Montauban, France, 82000
Contact: Jean-Louis Payen, MD    33-5-6392-8119    jl.payen@ch-montauban.fr   
Principal Investigator: Jean-Louis Payen, MD         
Service d'Hépatogastroentérologie - CH Montélimar Recruiting
Montelimar, France, 26200
Contact: Bernard Nalet, MD    33-4-7553-4058    bernard.nalet@ch-montélimar.fr   
Principal Investigator: Bernard Nalet, MD         
Service d'Hépatogastroentérologie - Hôpital Saint Eloi Recruiting
Montpellier, France, 34295
Contact: Dominique Larrey, MD    33-4-6733-7062    dom-larrey@chu-montpellier.fr   
Principal Investigator: Dominique Larrey, MD         
Sub-Investigator: Georges Pageaud, MD         
Service d'Hépatogastroentérologie - Hôpital Nord Laennec Recruiting
Nantes, France, 44093
Contact: Jérôme Gournay, MD    33-2-4016-5683    jérôme.gournay@chu-nantes.fr   
Principal Investigator: Jérôme Gournay, MD         
Sub-Investigator: Karine Richou, MD         
Service d'Hépatogastroentérologie - Hôpital de la Source Recruiting
Orléans, France, 45067
Contact: Xavier Causse, MD    33-2-3851-4245    xavier.causse@chr-orleans.fr   
Principal Investigator: Xavier Causse, MD         
Sub-Investigator: Nafa Si Ahmed, MD         
Service d'Hépatogastroentérologie - Hôpital Necker Recruiting
Paris, France, 75015
Contact: Stanislas Pol, MD    33-1-4449-4438    stanislas.pol@nck.aphp.fr   
Principal Investigator: Stanislas Pol, MD         
Sub-Investigator: Hélène Fontaine, MD         
Service d'Hépatogastroentérologie - Hôpital La Pitié Salpétrière Recruiting
Paris, France, 75013
Contact: Thierry Poynard, MD    33-1-4216-1002    tpoynard@teaser.fr   
Principal Investigator: Thierry Poynard, MD         
Sub-Investigator: Pascal Lebray, MD         
Service d'Hépatogastroentérologie - Hôpital Tenon Recruiting
Paris, France, 75020
Contact: Jean-Didier Grange, MD    33-1-5601-6404    jean-didier.grange@tnn.aphp.fr   
Principal Investigator: Jean-Didier Grange, MD         
Sub-Investigator: Xavier Amiot, MD         
Service d'Hépatogastroentérologie - Hôpital Cochin Recruiting
Paris, France, 75014
Contact: Philippe Sogni, MD    33-1-5841-1952    philippe.sogni@cch.aphp.fr   
Principal Investigator: Philippe Sogni, MD         
Sub-Investigator: Philippe Podevin, MD         
Service d'Hépatogastroentérologie et d'Assistance nutritive - Hôpital Haut-Lévêque Recruiting
Pessac, France, 33604
Contact: Victor De Ledinghen, MD    33-5-5765-6439    victor.deledinghen@chu-bordeaux.fr   
Principal Investigator: Victor De Ledinghen, MD         
Sub-Investigator: Juliette Foucher, MD         
Service d'Hépatogastroentérologie - Hôpital Pontchaillou Recruiting
Rennes, France, 35033
Contact: Dominique Guyader, MD    33-2-9928-4297    Dominique.Guyader@univ-rennes1.fr   
Principal Investigator: Dominique Guyader, MD         
Sub-Investigator: Yves Deugnier, MD         
Service d'Hépatogastroentérologie - CHU Rouen Recruiting
Rouen, France, 76031
Contact: Ghassan Riachi, MD    33-2-3288-8101    ghassan.riachi@chu-rouen.fr   
Principal Investigator: Ghassan Riachi, MD         
Sub-Investigator: Odile Goria, MD         
Service d'Hépatogastroentérologie - CH Saint Dizier Recruiting
Saint Dizier, France, 52115
Contact: Pascal Melin, MD    33-3-2556-8558    pascal.melin@wanadoo.fr   
Principal Investigator: Pascal Melin, MD         
Sub-Investigator: Schoeny, MD         
Service d'Hépatogastroentérologie, Clinique médicale B - Hôpital Civil Recruiting
Strasbourg, France, 67000
Contact: Michel Doffoel, MD    33-3-8811-5244    michel.doffoel@chru-strasbourg.fr   
Principal Investigator: Michel Doeffel, MD         
Sub-Investigator: François Habersezter, MD         
Service d'Hépatogastroentérologie - Hôpital Purpan Recruiting
Toulouse, France, 31059
Contact: Jean-Pierre Vinel, MD    33-5-6177-2114    vinel.jp@chu-toulouse.fr   
Contact: Laurent Alric, MD       alric.l@chu-toulouse.fr   
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    jp.bronowicki@chu-nancy.fr   
Principal Investigator: Jean-Pierre Bronowicki, MD         
Sub-Investigator: Laurence Chone, MD         
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Schering-Plough
Rennes University Hospital
Investigators
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
ClinicalTrials.gov 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
Fibrosis
Hepatitis
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
Ribavirin
Peginterferon alfa-2b
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014