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.
- Conditions
- Liver FibrosisHepatitis C, Chronic
- Interventions
- Registration Number
- NCT00323804
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 372
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Randomised PegIFN alfa 2b + ribavirin (RBV) arm Ribavirin 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 Randomised PegIFN alfa 2b + ribavirin-placebo arm Peginterferon alfa-2b 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 Randomised PegIFN alfa 2b + ribavirin-placebo arm Ribavirin-Placebo 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 Randomised PegIFN alfa 2b + ribavirin (RBV) arm Peginterferon alfa-2b 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
- Primary Outcome Measures
Name Time Method Rate of patients with at least a one point improvement in Metavir fibrosis score between the inclusion and the end-of-study liver biopsies. Screen visit and M36
- Secondary Outcome Measures
Name Time Method Safety of treatment and quality of life day0, M6, M12, M24, M36 Rate of patients with loss of detectable hepatitis C virus RNA Day 0 to M36 Distribution of the Chevallier fibrosis score Screen visit and M36 Evolution of the area of fibrosis between the inclusion and the end-of -study biopsies Screen visit and M36 Liver elasticity before and after treatment Screen,M12, M24, M36 Evolution of the hepatitis C viral load Screen to M36 Distribution of the Metavir scoring on the end-of-study biopsy M36 Fibrosis serum markers Screen, day0, M6, M12, M24, M36 Frequency of occurrence of hepatic complications and/or liver transplantations Day 0 to M36
Trial Locations
- Locations (43)
Service d'Hépatogastroentérologie - CH La Roche sur Yon
🇫🇷La Roche sur Yon, France
Service d'Hépatogastroentérologie - CH Montélimar
🇫🇷Montelimar, France
Centre Hospitalier
🇫🇷Saint Quentin, France
Service d'Hépatogastroentérologie - Hôpital du Bocage
🇫🇷Dijon, France
Service d'Hépatogastroentérologie - Hôpital Saint Eloi
🇫🇷Montpellier, France
Service d'Hépatogastroentérologie - Hôpital de la Source
🇫🇷Orléans, France
Service d'Hépatogastroentérologie - Hôpital La Pitié Salpétrière
🇫🇷Paris, France
Hôpital Purpan
🇫🇷Toulouse, France
CHU Sart Tilman
🇧🇪Liège, Belgium
Service d'Hépatogastroentérologie et d'endoscopie digestive - CH du Pays d'Aix
🇫🇷Aix en Provence, France
Service d'Hépatogastroentérologie - Hôpital Nord
🇫🇷Amiens, France
Service d'Hépatologie - Gastroentérologie - Cancérologie digestive - CHU Angers
🇫🇷Angers, France
Service d'Hépatogastroentérologie - Hôpital Avicenne
🇫🇷Bobigny, France
Service d' Hépatogastroentérologie - Hôpital Jean Verdier
🇫🇷Bondy, France
Service d'Hépatogastroentérologie et d'Assistance nutritive - Hôpital Haut-Lévêque
🇫🇷Bordeaux Pessac, France
Service des Maladies du Foie et de l'appareil Digestif - Hôpital de Bicêtre
🇫🇷Le Kremlin-Bicêtre, France
Département d'Hépatogastroentérologie - CH Le Mans
🇫🇷Le Mans, France
Service d'Hépatogastroentérologie - CHRU - Hôpital Claude Huriez
🇫🇷Lille, France
Service d'Hépatogastroentérologie - Hotel de la Croix Rousse
🇫🇷Lyon, France
Service d'Hépatogastroentérologie - Hôpital Pontchaillou
🇫🇷Rennes, France
Service d'Hépatogastroentérologie - CHU Rouen
🇫🇷Rouen, France
Service d'Hépatogastroentérologie, Clinique médicale B - Hôpital Civil
🇫🇷Strasbourg, France
Service d'Hépatogastroentérologie - Hôpital Tenon
🇫🇷Paris, France
Service d'Hépatogastroentérologie - Hôpital Trousseau
🇫🇷Tours, France
Service d'Hépatogastroentérologie - Hôpital Brabois
🇫🇷Vandoeuvre les Nancy, France
Hôpita Paul Brousse
🇫🇷Villejuif, France
Hôpital Erasme
🇧🇪Bruxelles, Belgium
CHU Brugmann
🇧🇪Bruxelles, Belgium
Hôpital Bracops
🇧🇪Bruxelles, Belgium
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil, France
Hôpital Nord
🇫🇷Grenoble, France
CH Pierre OUDOT
🇫🇷Bourgoin-Jallieu, France
Service d'Hépatogastroentérologie - Hôpital Beaujon
🇫🇷Clichy, France
Service d'Hépatogastroentérologie - Hôpital de la Cavale Blanche
🇫🇷Brest, France
Service d'Hépatologie - Gastroentérologie - Nutrition -Hôpital de la Côte de Nacre
🇫🇷Caen, France
Service d'Hépatogastroentérologie - CHU d'ESTAING
🇫🇷Clermont-Ferrand, France
Service d'Hépatogastroentérologie - CH Sud Francilien
🇫🇷Corbeil-Essonnes, France
Service d'Hépatogastroentérologie - Hôpital Saint Joseph
🇫🇷Marseille, France
Service d'Hépatogastroentérologie - CH Montauban
🇫🇷Montauban, France
Service d'Hépatogastroentérologie - Hôtel Dieu
🇫🇷Nantes, France
Hôpital de l'Archet
🇫🇷Nice, France
Service d'Hépatogastroentérologie - Hôpital Purpan
🇫🇷Toulouse, France
Hôpital de Jolimont
🇧🇪La Louvière, Belgium