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

This study has been terminated.
(Preliminary analysis)
Sponsor:
Information provided by (Responsible Party):
Agustin Albillos, Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier:
NCT00840489
First received: February 9, 2009
Last updated: January 30, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
 Drug: Ribavirin
Drug: Colchicine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hospital Universitario Ramon y Cajal:

Primary Outcome Measures:
  • 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: January 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ribavirin
Ribavirin 1000-1200 mg qd
 Drug: Ribavirin
Ribavirin 1000-1200 mg qd for 24 weeks
Other Name: Rebetol
Active Comparator: Colchicine
Colchicine 0.5 mg bd
 Drug: Colchicine
Colchicine 0.5 mg bd for 24 weeks
Other Name: Colchimax

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00840489

Locations
Spain
Hospital Universitario Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario Puerta de Hierro-Majadahonda
Madrid, Spain, 28222
Hospital General Universitario Gregorio Marañón
Madrid, Spain, 28007
Sponsors and Collaborators
Hospital Universitario Ramon y Cajal
Investigators
Principal Investigator: Agustín Albillos, MD Hospital Universitario Ramón y Cajal
Study Director: José Luis Calleja, MD Hospital Universitario Puerta de Hierro Majadahonda
Study Director: Rafael Bañares, MD Hospital General Universitario Gregorio Marañón
  More Information

No publications provided

Responsible Party: Agustin Albillos, Professor of Medicine, Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier: NCT00840489     History of Changes
Other Study ID Numbers: RIBACIR-1
Study First Received: February 9, 2009
Last Updated: January 30, 2013
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Fibrosis
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Pathologic Processes
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
 Colchicine
Ribavirin
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites

ClinicalTrials.gov processed this record on May 19, 2013