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

NCT00840489 | Terminated Phase 2

• 1 other identifier: RIBACIR-1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Chronic Hepatitis C

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels.

  24 weeks

Study Arms (2)

Ribavirin

EXPERIMENTAL

Ribavirin 1000-1200 mg qd

Drug: Ribavirin

Colchicine

ACTIVE COMPARATOR

Colchicine 0.5 mg bd

Drug: Colchicine

Interventions

Ribavirin DRUG

Ribavirin 1000-1200 mg qd for 24 weeks

Also known as: Rebetol

Ribavirin

Colchicine DRUG

Colchicine 0.5 mg bd for 24 weeks

Also known as: Colchimax

Colchicine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Universitario Ramon y Cajal: lead

Study Sites (3)

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Universitario Puerta de Hierro-Majadahonda

Madrid, Madrid, 28222, Spain

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Ribavirin; Colchicine; colchimax

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Alkaloids; Heterocyclic Compounds

Study Officials

• Agustín Albillos, MD

  Hospital Universitario Ramón y Cajal

  PRINCIPAL INVESTIGATOR

• José Luis Calleja, MD

  Hospital Universitario Puerta de Hierro Majadahonda

  STUDY DIRECTOR

• Rafael Bañares, MD

  Hospital General Universitario Gregorio Marañón

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 9, 2009
• First Posted: February 10, 2009
• Study Start: January 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 31, 2013

Record last verified: 2013-01

Locations

ES (3)