NCT01195181

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
506

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Sep 2005

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2005

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2009

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2010

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

August 31, 2010

Completed
6 days until next milestone

First Posted

Study publicly available on registry

September 6, 2010

Completed
Last Updated

September 6, 2010

Status Verified

September 1, 2010

Enrollment Period

4.3 years

First QC Date

August 31, 2010

Last Update Submit

September 3, 2010

Conditions

Hepatitis C VirusChronic Liver DiseaseViral HepatitisTherapeutic UsesAntiviral Agents

Keywords

peginterferon alfa 2a and 2b typeribavirinchronic hepatitis Cantiviral therapy cost/efficacyviral kinetics

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • 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.

Study Arms (2)

peginterferon alfa-2a plus ribavirin

ACTIVE COMPARATOR

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-2b plus ribavirin

ACTIVE COMPARATOR

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

Interventions

peginterferon plus ribavirinDRUG

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.

Also known as: Pegasys, PegIntron, Copegus, Rebetol
peginterferon alfa-2a plus ribavirinpeginterferon alfa-2b plus ribavirin

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Naive adult subject
  • active HCV infection (HCV-RNA positive)
  • histological/biochemical signs of chronic hepatitis or compensated cirrhosis
  • willingness of treatment

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Clinical and Experimental Medicine, Out-patients Hepatologic Unit, Azienda Ospedaliera di Padova.

Padua, 35100, Italy

Location

Related Publications (1)

  • Alberti A, Chemello L. and Benvegnù L. Natural history of hepatitis C. J Hepatol. 1999;31:17. Stroffolini T, Andreone P, Andriulli A et al. Characteristics of hepatocellular carcinoma in Italy. J Hepatol. 1998;29:944. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virological response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Inter Med. 2007;147:677. Russo MW. and Fried MW. Side effects of therapy for chronic hepatitis C. Gastroenterology 2003;124:1711. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon-alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001; 358: 958. Caliceti P. Pharmacokinetics of pegylated interferons: What is misleading? Dig Liver Dis. 2004;36:S334. Di Bisceglie AM, Ghalib RH, Hamzeh FM. and Rustgi VK. Early virologic response after peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin treatment in patients with chronic hepatitis C. J Viral Hepatitis. 2007;14:721. Malone DC, Tran TT. and Poordad FF. Cost-efficacy analysis of peginterferon alfa-2b plus ribavirin compared with peginterferon alfa-2a plus ribavirin for the treatment of chronic hepatitis C. J Manag Care Pharm. 2005;11: 687. McHutchinson JG, Lawitz EJ, Shiffman ML, for the IDEAL Study Team. Peginterferon Alfa-2b or Alfa-2a with Ribavirin for treatment of hepatitis C infection. NEJM 2009;361(6):580. Hadziyannis SJ, Sette H.Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;2;140(5):346.

    BACKGROUND

MeSH Terms

Conditions

Hepatitis CHepatitis C, Chronic

Interventions

Ribavirinpeginterferon alfa-2apeginterferon alfa-2b

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System DiseasesHepatitis, ChronicChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Officials

  • liliana chemello, M.D., Ph.D.

    University of Padova

    STUDY CHAIR

  • luisa cavalletto, M.D., Ph.D.

    Azienda Ospedaliera di Padova

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

August 31, 2010

First Posted

September 6, 2010

Study Start

September 1, 2005

Primary Completion

December 1, 2009

Study Completion

August 1, 2010

Last Updated

September 6, 2010

Record last verified: 2010-09

Locations

IT(1)