Back to resultsInterest 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.
Primary Purpose
Hepatitis C, Chronic, Liver Fibrosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Peginterferon alfa-2b
Ribavirin
Ribavirin-Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Maintenance therapy, Non-responder patients, Ribavirin/peginterferon combination therapy, Hepatitis C, Chronic
Eligibility 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
Sites / Locations
- CHU Brugmann
- Hôpital Bracops
- Hôpital Erasme
- Hôpital de Jolimont
- CHU Sart Tilman
- Service d'Hépatogastroentérologie et d'endoscopie digestive - CH du Pays d'Aix
- Hôpital Nord
- Service d'Hépatogastroentérologie - Hôpital Nord
- Service d'Hépatologie - Gastroentérologie - Cancérologie digestive - CHU Angers
- Centre Hospitalier Victor Dupouy
- Service d'Hépatogastroentérologie - Hôpital Avicenne
- Service d' Hépatogastroentérologie - Hôpital Jean Verdier
- Service d'Hépatogastroentérologie et d'Assistance nutritive - Hôpital Haut-Lévêque
- CH Pierre OUDOT
- Service d'Hépatogastroentérologie - Hôpital de la Cavale Blanche
- Service d'Hépatologie - Gastroentérologie - Nutrition -Hôpital de la Côte de Nacre
- Centre Hospitalier
- Service d'Hépatogastroentérologie - CHU d'ESTAING
- Service d'Hépatogastroentérologie - Hôpital Beaujon
- Service d'Hépatogastroentérologie - CH Sud Francilien
- Service d'Hépatogastroentérologie - Hôpital du Bocage
- Hôpital Nord
- Service d'Hépatogastroentérologie - CH La Roche sur Yon
- Service des Maladies du Foie et de l'appareil Digestif - Hôpital de Bicêtre
- Département d'Hépatogastroentérologie - CH Le Mans
- Service d'Hépatogastroentérologie - CHRU - Hôpital Claude Huriez
- Service d'Hépatogastroentérologie - Hotel de la Croix Rousse
- Service d'Hépatogastroentérologie - Hôpital Saint Joseph
- Service d'Hépatogastroentérologie - CH Montauban
- Service d'Hépatogastroentérologie - CH Montélimar
- Service d'Hépatogastroentérologie - Hôpital Saint Eloi
- Service d'Hépatogastroentérologie - Hôtel Dieu
- Hôpital de l'Archet
- Service d'Hépatogastroentérologie - Hôpital de la Source
- Service d'Hépatogastroentérologie - Hôpital La Pitié Salpétrière
- Service d'Hépatogastroentérologie - Hôpital Tenon
- Service d'Hépatogastroentérologie - Hôpital Pontchaillou
- Service d'Hépatogastroentérologie - CHU Rouen
- Centre Hospitalier
- Service d'Hépatogastroentérologie, Clinique médicale B - Hôpital Civil
- Hôpital Purpan
- Service d'Hépatogastroentérologie - Hôpital Purpan
- Service d'Hépatogastroentérologie - Hôpital Trousseau
- Service d'Hépatogastroentérologie - Hôpital Brabois
- Hôpita Paul Brousse
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Randomised PegIFN alfa 2b + ribavirin (RBV) arm
Randomised PegIFN alfa 2b + ribavirin-placebo arm
Arm Description
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
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
Outcomes
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
Full Information
NCT ID
NCT00323804
First Posted
May 9, 2006
Last Updated
September 3, 2014
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Merck Sharp & Dohme LLC, Rennes University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00323804
Brief Title
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.
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.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Merck Sharp & Dohme LLC, Rennes University Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic, Liver Fibrosis
Keywords
Maintenance therapy, Non-responder patients, Ribavirin/peginterferon combination therapy, Hepatitis C, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
372 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Randomised PegIFN alfa 2b + ribavirin (RBV) arm
Arm Type
Experimental
Arm Description
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
Arm Title
Randomised PegIFN alfa 2b + ribavirin-placebo arm
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Peginterferon alfa-2b
Intervention Description
PegIFN alfa 2b in addition to ribavirin or ribavirin-placebo, from day 0 to M36
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
Ribavirin in addition to PegIFN alfa 2b, from day 0 to M36
Intervention Type
Drug
Intervention Name(s)
Ribavirin-Placebo
Intervention Description
Ribavirin-placebo in addition to PegIFN alfa 2b, from day 0 to M36
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Distribution of the Metavir scoring on the end-of-study biopsy
Time Frame
M36
Title
Distribution of the Chevallier fibrosis score
Time Frame
Screen visit and M36
Title
Evolution of the area of fibrosis between the inclusion and the end-of -study biopsies
Time Frame
Screen visit and M36
Title
Fibrosis serum markers
Time Frame
Screen, day0, M6, M12, M24, M36
Title
Liver elasticity before and after treatment
Time Frame
Screen,M12, M24, M36
Title
Safety of treatment and quality of life
Time Frame
day0, M6, M12, M24, M36
Title
Frequency of occurrence of hepatic complications and/or liver transplantations
Time Frame
Day 0 to M36
Title
Evolution of the hepatitis C viral load
Time Frame
Screen to M36
Title
Rate of patients with loss of detectable hepatitis C virus RNA
Time Frame
Day 0 to M36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominique Guyader, MD, PhD
Organizational Affiliation
CHU Rennes
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eric Bellissant, MD, PhD
Organizational Affiliation
CHU Rennes
Official's Role
Study Chair
Facility Information:
Facility Name
CHU Brugmann
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Hôpital Bracops
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Hôpital Erasme
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Hôpital de Jolimont
City
La Louvière
ZIP/Postal Code
7100
Country
Belgium
Facility Name
CHU Sart Tilman
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Service d'Hépatogastroentérologie et d'endoscopie digestive - CH du Pays d'Aix
City
Aix en Provence
ZIP/Postal Code
13616
Country
France
Facility Name
Hôpital Nord
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Nord
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
Service d'Hépatologie - Gastroentérologie - Cancérologie digestive - CHU Angers
City
Angers
ZIP/Postal Code
49100
Country
France
Facility Name
Centre Hospitalier Victor Dupouy
City
Argenteuil
ZIP/Postal Code
95100
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Avicenne
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
Service d' Hépatogastroentérologie - Hôpital Jean Verdier
City
Bondy
ZIP/Postal Code
93143
Country
France
Facility Name
Service d'Hépatogastroentérologie et d'Assistance nutritive - Hôpital Haut-Lévêque
City
Bordeaux Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
CH Pierre OUDOT
City
Bourgoin-Jallieu
ZIP/Postal Code
38317
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital de la Cavale Blanche
City
Brest
ZIP/Postal Code
29200
Country
France
Facility Name
Service d'Hépatologie - Gastroentérologie - Nutrition -Hôpital de la Côte de Nacre
City
Caen
ZIP/Postal Code
14000
Country
France
Facility Name
Centre Hospitalier
City
Châteauroux
ZIP/Postal Code
36000
Country
France
Facility Name
Service d'Hépatogastroentérologie - CHU d'ESTAING
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Service d'Hépatogastroentérologie - CH Sud Francilien
City
Corbeil-Essonnes
ZIP/Postal Code
91106
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital du Bocage
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Hôpital Nord
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Service d'Hépatogastroentérologie - CH La Roche sur Yon
City
La Roche sur Yon
ZIP/Postal Code
85925
Country
France
Facility Name
Service des Maladies du Foie et de l'appareil Digestif - Hôpital de Bicêtre
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94275
Country
France
Facility Name
Département d'Hépatogastroentérologie - CH Le Mans
City
Le Mans
ZIP/Postal Code
72037
Country
France
Facility Name
Service d'Hépatogastroentérologie - CHRU - Hôpital Claude Huriez
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hotel de la Croix Rousse
City
Lyon
ZIP/Postal Code
69004
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Saint Joseph
City
Marseille
ZIP/Postal Code
13285
Country
France
Facility Name
Service d'Hépatogastroentérologie - CH Montauban
City
Montauban
ZIP/Postal Code
82000
Country
France
Facility Name
Service d'Hépatogastroentérologie - CH Montélimar
City
Montelimar
ZIP/Postal Code
26200
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Saint Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôtel Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hôpital de l'Archet
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital de la Source
City
Orléans
ZIP/Postal Code
45067
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital La Pitié Salpétrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Tenon
City
Paris
ZIP/Postal Code
75020
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Service d'Hépatogastroentérologie - CHU Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Centre Hospitalier
City
Saint Quentin
ZIP/Postal Code
02321
Country
France
Facility Name
Service d'Hépatogastroentérologie, Clinique médicale B - Hôpital Civil
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Name
Hôpital Purpan
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Purpan
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Trousseau
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Brabois
City
Vandoeuvre les Nancy
ZIP/Postal Code
54500
Country
France
Facility Name
Hôpita Paul Brousse
City
Villejuif
ZIP/Postal Code
94804
Country
France
12. IPD Sharing Statement
Learn more about this trial
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.
We'll reach out to this number within 24 hrs