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

Study Overview
=================
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.

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

Conditions
-----------------
Chronic Hepatitis C

Intervention / Treatment
-----------------
* Drug: Ribavirin
* Drug: Colchicine


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ribavirin<br>Ribavirin 1000-1200 mg qd | Drug: Ribavirin<br>* Ribavirin 1000-1200 mg qd for 24 weeks<br>* Other names: Rebetol;|
| Active Comparator: Colchicine<br>Colchicine 0.5 mg bd | Drug: Colchicine<br>* Colchicine 0.5 mg bd for 24 weeks<br>* Other names: Colchimax;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels. |  | 24 weeks |