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

Phase II Trial of Long-term Monotherapy With Ribavirin Against Colchicine on Progression of Chronic Hepatitis C With Advanced Fibrosis in Patients With Non-response to Standard Antiviral Therapy

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Ribavirin; Drug: Colchicine

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro-Majadahonda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ribavirin; Ribavirin 1000-1200 mg qd	Drug: Ribavirin; Ribavirin 1000-1200 mg qd for 24 weeks; Other Names: Rebetol
Active Comparator: Colchicine; Colchicine 0.5 mg bd	Drug: Colchicine; Colchicine 0.5 mg bd for 24 weeks; Other Names: Colchimax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels.	24 weeks

Collaborators and Investigators

• Sponsor: Hospital Universitario Ramon y Cajal
• Investigators: Principal Investigator: Agustin Albillos, MD, Hospital Universitario Ramon y Cajal; Study Director: José Luis Calleja, MD, Hospital Universitario Puerta de Hierro Majadahonda; Study Director: Rafael Bañares, MD, Hospital General Universitario Gregorio Marañon

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 9, 2009
• First Submitted That Met QC Criteria: February 9, 2009
• First Posted (Estimate): February 10, 2009

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 30, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antirheumatic Agents; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Ribavirin; Colchicine
• Other Study ID Numbers: RIBACIR-1