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

Sponsor

Hospital Universitario Ramon y Cajal (Other)

Overall Status

Terminated

CT.gov ID

NCT00840489

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

16.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Jan 1, 2009

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

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

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

Outcome Measures

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 [24 weeks]

Secondary Outcome Measures

Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels. [24 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Hospital General Universitario Gregorio Marañón	Madrid	Spain	28007
2	Hospital Universitario Ramon y Cajal	Madrid	Spain	28034
3	Hospital Universitario Puerta de Hierro-Majadahonda	Madrid	Spain	28222

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