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

This study has been completed.
Sponsor:
Collaborators:
Regione Veneto
University of Padua
Information provided by:
Azienda Ospedaliera di Padova
ClinicalTrials.gov Identifier:
NCT01195181
First received: August 31, 2010
Last updated: September 3, 2010
Last verified: September 2010
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera di Padova:

Primary Outcome Measures:
  • Evaluation of real dose drugs intake in relation to sustained virological response (SVR). [ Time Frame: Measurement of HCV-RNA at 24° week after therapy withdrawal. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Measurement of HCV-RNA during therapy in relation to negativity at 24° week after therapy withdrawal. ] [ Designated as safety issue: No ]
    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.


Enrollment: 506
Study Start Date: September 2005
Study Completion Date: August 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01195181

Locations
Italy
Department of Clinical and Experimental Medicine, Out-patients Hepatologic Unit, Azienda Ospedaliera di Padova.
Padua, Italy, 35100
Sponsors and Collaborators
Azienda Ospedaliera di Padova
Regione Veneto
University of Padua
Investigators
Study Chair: liliana chemello, M.D., Ph.D. University of Padua
Principal Investigator: luisa cavalletto, M.D., Ph.D. Azienda Ospedaliera di Padova
  More Information

No publications provided

Responsible Party: Liliana Chemello, M.D, Ph.D., Scientific Director, Department of Clinical and Experimental Medicine, University of Padua. Italy
ClinicalTrials.gov Identifier: NCT01195181     History of Changes
Other Study ID Numbers: HEPCOVE protocol, DRG N.2920/2002
Study First Received: August 31, 2010
Last Updated: September 3, 2010
Health Authority: Italy: Ethics Committee

Keywords provided by Azienda Ospedaliera di Padova:
peginterferon alfa 2a and 2b type
ribavirin
chronic hepatitis C
antiviral therapy cost/efficacy
viral kinetics

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Peginterferon alfa-2a
Peginterferon alfa-2b
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014