Efficacy of Long-term Ribavirin in Non-responders With Chronic Hepatitis C and Advanced Fibrosis

Phase 2

Terminated

• Conditions: Chronic Hepatitis C
• Interventions: Drug: Colchicine; Drug: Ribavirin

• Registration Number: NCT00840489
• Lead Sponsor: Hospital Universitario Ramon y Cajal

Brief Summary

The rate of sustained virological response to a course of standard antiviral therapy (peg-interferon plus ribavirin) of patients with chronic hepatitis C infected by genotype 1 with advanced fibrosis (\>F2) is rather low. Monotherapy with ribavirin reduces ALT levels and necroinflammatory liver activity in up to a half of non-responders to standard antiviral therapy, but without changes in liver fibrosis or viremia. Such a beneficial effect seems to be mainly due to the immunomodulatory effect of ribavirin. Portal pressure, as measured by HVPG, lowers in patients with chronic hepatitis C and advanced fibrosis with end-of-treatment response to peg-interferon plus ribavirin. Portal pressure reduction in this setting relates to a reduction of the necroinflammatory liver activity, but not with fibrosis amelioration. We hypothesize that monotherapy with ribavirin reduces portal pressure in hepatitis C patients with advanced fibrosis by means of its immunomodulatory and anti-inflammatory effects, and could constitute an alternative to non-responders to standard antiviral treatment. Portal pressure measurement has become a validated surrogate outcome measure in chronic liver disease, since decreasing portal pressure has shown consistent improvement in survival and clinical outcomes, such as complications of portal hypertension. The primary aim of this study is to investigate whether ribavirin monotherapy slows the progression of advanced chronic liver disease by hepatitis C as assessed by a reduction in HVPG.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-02-09
• Study First Submitted QC: 2009-02-09
• Study First Posted: 2009-02-10
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-30
• Last Update Posted: 2013-01-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• HCV RNA in serum
• AST/ALT greater than the upper limit of normal range
• HVPG >5 mm Hg
• Non-response or contraindication to a standard course of antiviral therapy

Exclusion Criteria

• Active alcoholism
• HIV infection
• Serum creatinine >1.2 mg/dl, hemoglobin <11 g/dl, hemolysis, symptomatic ischemic heart disease or cerebrovascular disease
• Decompensated chronic liver disease
• Pregnancy
• Hypersensitivity to the drugs of the study
• Severe concomitant disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine	Colchicine	Colchicine 0.5 mg bd
Ribavirin	Ribavirin	Ribavirin 1000-1200 mg qd

Primary Outcome Measures

Name	Time	Method
Hepatic disease progression defined by a difference of >2 mmHg in the hepatic venous gradient between the basal values and the end of treatment values in both groups	24 weeks

Secondary Outcome Measures

Name	Time	Method
Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels.	24 weeks

Trial Locations

Locations (3)

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro-Majadahonda; 🇪🇸 Madrid, Spain