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

Chronic Hepatitis C Clinical Trial

— RIBACIR  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00840489
• Other study ID #: RIBACIR-1
• Status: Terminated
• Phase: Phase 2
• First received: February 9, 2009
• Last updated: January 30, 2013
• Start date: January 2009
• Est. completion date: December 2012

Study information

• Verified date: January 2013
• Source: Hospital Universitario Ramon y Cajal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Ribavirin
Ribavirin 1000-1200 mg qd for 24 weeks
• Colchicine
Colchicine 0.5 mg bd for 24 weeks

Locations

Country	Name	City	State
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Puerta de Hierro-Majadahonda	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels.		24 weeks	No