Different PEG-interferon and Ribavirin Schedules for Chronic Hepatitis C in the Real Clinical Practice.

Study Overview
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Brief Summary
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Hepatitis C virus (HCV) infection provokes thousands of deaths every year all over the world, being the major cause of progressive liver disease, primary hepatic cancer and liver transplantation. Today, a curative therapy is available, that can eradicate the viral infection and determine the regression of liver fibrosis, also in cirrhotic subjects. The current standard-of-care for HCV chronic infection is combination therapy with peginterferon (P-IFN) and ribavirin (RBV). However, this treatment is not only expensive but determines several side effects, that can reduce drug tolerance and hence, patient adherence to therapy. There are two types of available P-IFN on the market: P-IFN alfa-2a (Pegasys®, F.Hoffmann-La Roche) administered at a flat-dose of 180 mcg/week and P-IFN alfa-2b (PegIntron®, Schering-Plough) given at a weight-based dose of 50 to 150 mcg/week. Since only a single amino acid differentiates these types of IFN, administration strategies depend on their pegilation with molecules of 40 or 12kDa, respectively, that accounts for differences in the pharmacokinetic and pharmacodynamic drug-profile and influences probably also bioactivity. No comparative data are available on the benefits and costs of the licensed Peg-IFN plus RBV for the treatment of HCV infection in the real clinical practice, even if, the benefit and favourable cost-efficacy of this antiviral therapy is well established and of large consensus. Recently, the first randomized controlled mega-trial to compare antiviral therapeutic efficacy in naïve patients with HCV-genotype 1 infection during different regimens of P-IFN alfa-2b (at low and standard-dose) and P-IFN alfa-2a plus RBV, has been published, confirming a similar efficacy, of around 40%, obtained with the three schedules evaluated. In Italy, a regional program on the Surveillance and Control of HCV Infection, set up by the Regional Health Councillorship, has led to the development of a clinical and epidemiological observatory, constituted by a network of liver tertiary centres (Hepatological Cooperative Network of Veneto, HepCoVe). This collaborative group is connected on-line by a common database that, since 2003, has prospectively collected data on a cohort of more than 3000 patients with chronic HCV infection and, among them, of 506 naïve subjects that consecutively underwent combination therapy with P-IFN alfa-2a or alfa-2b plus RBV. The aim of this study was to rationalize and improve the social regional health program on antiviral treatment of chronic hepatitis C by assessing the different schedules utilization of P-IFN plus RBV as well as the respective therapeutic effectiveness, safety and costs in the real clinical practice (Project A).

Detailed Description
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(Project B) To evaluate the viral kinetic decay during antiviral combination therapy with P-IFN alfa-2a and 2b type plus ribavirin.

Official Title
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Improvement of the Surveillance and Control of Liver Disease and Complication Due to Chronic Hepatitis C: Project A) Antiviral Drugs Use, Efficacy, Safety and Costs; Project B) Kinetics of Virological Response.

Conditions
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Hepatitis C Virus, Chronic Liver Disease, Viral Hepatitis, Therapeutic Uses, Antiviral Agents

Intervention / Treatment
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* Drug: peginterferon plus ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Naive adult subject active HCV infection (HCV-RNA positive) histological/biochemical signs of chronic hepatitis or compensated cirrhosis willingness of treatment Exclusion Criteria: autoimmune disorders severe depression or psychiatric disease previous decompensation of cirrhosis gastroesophageal bleeding hepatocellular carcinoma major disease with a life expectancy of less than 5 years pregnancy or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: peginterferon alfa-2a plus ribavirin<br>patients will receive a fixed dose of 180ug/week of peginterferon alfa-2a plus ribavirin at 15mg/kg/daily. | Drug: peginterferon plus ribavirin<br>* peginterferon alfa-2a at 180ug/week (preempt syringe, sc) or peginterferon alfa-2b at 1,5 ug/kg/week (standard dose) or at 1,0 ug/kg/week (lower dose)(preempt pen, sc) for 24 or 48 week in relation to HCV genotype plus ribavirin (capsules, po) at 15mg/kg/daily combination therapy.<br>* Other names: Rebetol;|
| Active Comparator: peginterferon alfa-2b plus ribavirin<br>patients will receive a weight adjusted dose (1,5ug/kg) from 50 to 150ug/week of peginterferon alfa-2b (standard dose) or a lower dose (1,0ug/kg) at physician discretion (randomization list available only for 100 cases) plus ribavirin at 15mg/kg/daily. | Drug: peginterferon plus ribavirin<br>* peginterferon alfa-2a at 180ug/week (preempt syringe, sc) or peginterferon alfa-2b at 1,5 ug/kg/week (standard dose) or at 1,0 ug/kg/week (lower dose)(preempt pen, sc) for 24 or 48 week in relation to HCV genotype plus ribavirin (capsules, po) at 15mg/kg/daily combination therapy.<br>* Other names: Rebetol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of real dose drugs intake in relation to sustained virological response (SVR). | Project A) The analysis will describe the efficacy (SVR) and costs of the 3 different antiviral schedules proposed. | Measurement of HCV-RNA at 24° week after therapy withdrawal. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the profile of the virus decay during antiviral therapy in relation to virological response. | Project B) The analysis will evaluate the kinetics of virological response obtained with the two peginterferons plus ribavirin by HCV-RNA quantification (Cobas,TaqMan, Roche) at basal time and at 1°,4°,12°,24°,36°,48° week during therapy and at 24° week after therapy withdrawal. | Measurement of HCV-RNA during therapy in relation to negativity at 24° week after therapy withdrawal. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peginterferon alfa 2a and 2b type, ribavirin, chronic hepatitis C, antiviral therapy cost/efficacy, viral kinetics