Clinical trial NCT00840489: Efficacy of Long-term Ribavirin in Non-responders With Chronic Hepatitis C and Advanced Fibrosis
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Lead sponsor: Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2009-02-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: 24 weeks
Secondary outcomes:
measure: Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
Study officials:
affiliation: Hospital Universitario Ramón y Cajal
name: Agustín Albillos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Puerta de Hierro Majadahonda
name: José Luis Calleja, MD
role: STUDY_DIRECTOR
affiliation: Hospital General Universitario Gregorio Marañón
name: Rafael Bañares, MD
role: STUDY_DIRECTOR
References: