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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00840489
Recruitment Status : Terminated (Preliminary analysis)
First Posted : February 10, 2009
Last Update Posted : January 31, 2013
Information provided by (Responsible Party):
Agustin Albillos, 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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Drug: Ribavirin Drug: Colchicine Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : January 2009
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  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 [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels. [ Time Frame: 24 weeks ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00840489

Hospital General Universitario Gregorio Marañón
Madrid, Spain, 28007
Hospital Universitario Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario Puerta de Hierro-Majadahonda
Madrid, Spain, 28222
Sponsors and Collaborators
Hospital Universitario Ramon y Cajal
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

Responsible Party: Agustin Albillos, Professor of Medicine, Hospital Universitario Ramon y Cajal Identifier: NCT00840489     History of Changes
Other Study ID Numbers: RIBACIR-1
First Posted: February 10, 2009    Key Record Dates
Last Update Posted: January 31, 2013
Last Verified: January 2013

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