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.

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.

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00323804

Enrollment

372

Registered

2006-05-10

Start date

2006-05-31

Completion date

2013-03-31

Last updated

2014-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C, Chronic, Liver Fibrosis

Keywords

Maintenance therapy, Non-responder patients, Ribavirin/peginterferon combination therapy, Hepatitis C, Chronic

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.

Interventions

BIOLOGICALPeginterferon alfa-2b

PegIFN alfa 2b in addition to ribavirin or ribavirin-placebo, from day 0 to M36

DRUGRibavirin

Ribavirin in addition to PegIFN alfa 2b, from day 0 to M36

DRUGRibavirin-Placebo

Ribavirin-placebo in addition to PegIFN alfa 2b, from day 0 to M36

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

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.	Screen visit and M36

Secondary

Measure	Time frame
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
Fibrosis serum markers	Screen, day0, M6, M12, M24, M36
Liver elasticity before and after treatment	Screen,M12, M24, M36
Distribution of the Metavir scoring on the end-of-study biopsy	M36
Frequency of occurrence of hepatic complications and/or liver transplantations	Day 0 to M36
Evolution of the hepatitis C viral load	Screen to M36
Rate of patients with loss of detectable hepatitis C virus RNA	Day 0 to M36
Safety of treatment and quality of life	day0, M6, M12, M24, M36

Countries

Belgium, France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026