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.

September 3, 2014 updated by: ANRS, Emerging Infectious Diseases

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
372

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bruxelles, Belgium, 1070
        • Hopital Erasme
      • Bruxelles, Belgium, 1020
        • CHU Brugmann
      • Bruxelles, Belgium, 1070
        • Hôpital Bracops
      • La Louvière, Belgium, 7100
        • Hopital De Jolimont
      • Liège, Belgium, 4000
        • CHU Sart Tilman
  • France
      • Aix en Provence, France, 13616
        • Service d'Hépatogastroentérologie et d'endoscopie digestive - CH du Pays d'Aix
      • Amiens, France, 80054
        • Hôpital Nord
      • Amiens, France, 80054
        • Service d'Hépatogastroentérologie - Hôpital Nord
      • Angers, France, 49100
        • Service d'Hépatologie - Gastroentérologie - Cancérologie digestive - CHU Angers
      • Argenteuil, France, 95100
        • Centre Hospitalier Victor Dupouy
      • Bobigny, France, 93009
        • Service d'Hépatogastroentérologie - Hôpital Avicenne
      • Bondy, France, 93143
        • Service d' Hépatogastroentérologie - Hôpital Jean Verdier
      • Bordeaux Pessac, France, 33604
        • Service d'Hépatogastroentérologie et d'Assistance nutritive - Hôpital Haut-Lévêque
      • Bourgoin-Jallieu, France, 38317
        • CH Pierre Oudot
      • Brest, France, 29200
        • Service d'Hépatogastroentérologie - Hôpital de la Cavale Blanche
      • Caen, France, 14000
        • Service d'Hépatologie - Gastroentérologie - Nutrition -Hôpital de la Côte de Nacre
      • Châteauroux, France, 36000
        • Centre Hospitalier
      • Clermont-Ferrand, France, 63003
        • Service d'Hépatogastroentérologie - CHU d'ESTAING
      • Clichy, France, 92110
        • Service d'Hépatogastroentérologie - Hôpital Beaujon
      • Corbeil-Essonnes, France, 91106
        • Service d'Hépatogastroentérologie - CH Sud Francilien
      • Dijon, France, 21079
        • Service d'Hépatogastroentérologie - Hôpital du Bocage
      • Grenoble, France, 38043
        • Hôpital Nord
      • La Roche sur Yon, France, 85925
        • Service d'Hépatogastroentérologie - CH La Roche sur Yon
      • Le Kremlin-Bicêtre, France, 94275
        • Service des Maladies du Foie et de l'appareil Digestif - Hôpital de Bicêtre
      • Le Mans, France, 72037
        • Département d'Hépatogastroentérologie - CH Le Mans
      • Lille, France, 59000
        • Service d'Hépatogastroentérologie - CHRU - Hôpital Claude Huriez
      • Lyon, France, 69004
        • Service d'Hépatogastroentérologie - Hotel de la Croix Rousse
      • Marseille, France, 13285
        • Service d'Hépatogastroentérologie - Hôpital Saint Joseph
      • Montauban, France, 82000
        • Service d'Hépatogastroentérologie - CH Montauban
      • Montelimar, France, 26200
        • Service d'Hépatogastroentérologie - CH Montélimar
      • Montpellier, France, 34295
        • Service d'Hépatogastroentérologie - Hôpital Saint Eloi
      • Nantes, France, 44093
        • Service d'Hépatogastroentérologie - Hôtel Dieu
      • Nice, France, 06202
        • Hôpital de l'Archet
      • Orléans, France, 45067
        • Service d'Hépatogastroentérologie - Hôpital de la Source
      • Paris, France, 75013
        • Service d'Hépatogastroentérologie - Hôpital La Pitié Salpétrière
      • Paris, France, 75020
        • Service d'Hépatogastroentérologie - Hôpital Tenon
      • Rennes, France, 35033
        • Service d'Hépatogastroentérologie - Hôpital Pontchaillou
      • Rouen, France, 76031
        • Service d'Hépatogastroentérologie - CHU Rouen
      • Saint Quentin, France, 02321
        • Centre Hospitalier
      • Strasbourg, France, 67000
        • Service d'Hépatogastroentérologie, Clinique médicale B - Hôpital Civil
      • Toulouse, France, 31059
        • Hopital Purpan
      • Toulouse, France, 31059
        • Service d'Hépatogastroentérologie - Hôpital Purpan
      • Tours, France, 37044
        • Service d'Hépatogastroentérologie - Hôpital Trousseau
      • Vandoeuvre les Nancy, France, 54500
        • Service d'Hépatogastroentérologie - Hôpital Brabois
      • Villejuif, France, 94804
        • Hôpita Paul Brousse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Randomised PegIFN alfa 2b + ribavirin (RBV) arm
Combination of ribavirin capsules 200 mg, weight-based daily dose ( <75 kg : 1000 mg ; ≥ 75 kg : 1200 mg), and low-dose PegIFN alfa 2b by subcutaneous injection 0.5 μg / kg / week, from day 0 to M36
Biological: Peginterferon alfa-2b
PegIFN alfa 2b in addition to ribavirin or ribavirin-placebo, from day 0 to M36
Drug: Ribavirin
Ribavirin in addition to PegIFN alfa 2b, from day 0 to M36
Placebo Comparator: Randomised PegIFN alfa 2b + ribavirin-placebo arm
Combination of ribavirin-placebo capsules 200 mg, weight-based daily dose ( <75 kg : 1000 mg ; ≥ 75 kg : 1200 mg), and low-dose PegIFN alfa 2b by subcutaneous injection 0.5 μg / kg / week, from day 0 to M36
Biological: Peginterferon alfa-2b
PegIFN alfa 2b in addition to ribavirin or ribavirin-placebo, from day 0 to M36
Drug: Ribavirin-Placebo
Ribavirin-placebo in addition to PegIFN alfa 2b, from day 0 to M36

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Rate of patients with at least a one point improvement in Metavir fibrosis score between the inclusion and the end-of-study liver biopsies.
Time Frame: Screen visit and M36
Screen visit and M36

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Distribution of the Metavir scoring on the end-of-study biopsy
Time Frame: M36
M36
Distribution of the Chevallier fibrosis score
Time Frame: Screen visit and M36
Screen visit and M36
Evolution of the area of fibrosis between the inclusion and the end-of -study biopsies
Time Frame: Screen visit and M36
Screen visit and M36
Fibrosis serum markers
Time Frame: Screen, day0, M6, M12, M24, M36
Screen, day0, M6, M12, M24, M36
Liver elasticity before and after treatment
Time Frame: Screen,M12, M24, M36
Screen,M12, M24, M36
Safety of treatment and quality of life
Time Frame: day0, M6, M12, M24, M36
day0, M6, M12, M24, M36
Frequency of occurrence of hepatic complications and/or liver transplantations
Time Frame: Day 0 to M36
Day 0 to M36
Evolution of the hepatitis C viral load
Time Frame: Screen to M36
Screen to M36
Rate of patients with loss of detectable hepatitis C virus RNA
Time Frame: Day 0 to M36
Day 0 to M36

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ANRS, Emerging Infectious Diseases

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC
Rennes University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dominique Guyader, MD, PhD, Chu Rennes

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 9, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 10, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ANRS HC15 NRfi
  • 2005-002937-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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