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

Sponsor

Azienda Ospedaliera di Padova (Other)

Overall Status

Completed

CT.gov ID

NCT01195181

Collaborator

Regione Veneto (Other), University of Padova (Other)

506

Enrollment

Location

Arms

Duration (Months)

8.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus Chronic Liver Disease Viral Hepatitis Therapeutic Uses Antiviral Agents	Drug: peginterferon plus ribavirin	Phase 4

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

506 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: peginterferon alfa-2a plus ribavirin patients will receive a fixed dose of 180ug/week of peginterferon alfa-2a plus ribavirin at 15mg/kg/daily.	Drug: peginterferon plus ribavirin 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. Other Names: Pegasys PegIntron Copegus Rebetol
Active Comparator: peginterferon alfa-2b plus ribavirin 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 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. Other Names: Pegasys PegIntron Copegus Rebetol

Arm

Intervention/Treatment

Active Comparator: peginterferon alfa-2a plus ribavirin

patients will receive a fixed dose of 180ug/week of peginterferon alfa-2a plus ribavirin at 15mg/kg/daily.

Drug: peginterferon plus ribavirin

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.

Other Names:

Pegasys

PegIntron

Copegus

Rebetol

Active Comparator: peginterferon alfa-2b plus ribavirin

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

Other Names:

Pegasys

PegIntron

Copegus

Rebetol

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Description of the profile of the virus decay during antiviral therapy in relation to virological response. [Measurement of HCV-RNA during therapy in relation to negativity at 24° week after therapy withdrawal.]
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.