Peginterferon Alfa-2a and Ribavirin for Genotype 2 Chronic Hepatitis C: Duration and Ribavirin Dose Stratified by RVR

June 3, 2014 updated by: National Taiwan University Hospital

Peginterferon Alfa-2a Plus Ribavirin in Patients With Genotype 2 Chronic Hepatitis C: A Randomized Study of Treatment Duration and Ribavirin Dose Stratified by Rapid Virologic Response

Treatment with peginterferon plus daily low dose (800 mg) or weight-based ribavirin (800-1400 mg) for 24 to 48 weeks has achieved 70-93% sustained virologic response (SVR) rates in patients with genotype 2 or 3 chronic hepatitis C (CHC). Recently, a large randomized study has shown that patients with genotype 2 or 3 CHC have comparable SVR rates for those who received peginterferon for 24 or 48 weeks, and who received daily low dose (800 mg) or standard dose (1000-1200 mg) ribavirin. Therefore, the currently recommended treatment for these patients is 24 weeks of peginterferon plus low dose ribavirin. Because of the high response rates, several studies have shown that when these patients had rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, at week 4 of peginterferon plus weight-based ribavirin, 12-16 weeks of treatment could have 82-94% SVR rates. However, treatment with peginterferon plus low dose ribavirin for 24 weeks showed significantly higher SVR rates than that for 16 weeks (85% versus 79%) in these patients who achieved RVR. While studies showed concordant results in SVR rates for patients with genotype 3 CHC who received peginterferon plus low dose or weight-based ribavirin for 16 or 24 weeks, the SVR rates stratified by RVR showed great differences in patients with genotype 2 CHC who received such treatment. Currently, there are no studies on the direct comparison of low dose versus weight-based ribavirin, and of 16 to 24 weeks of treatment stratified by RVR for patients with genotype 2 CHC. The investigators aimed to conduct a randomized trial to determine the optimal ribavirin dose and treatment duration of peginterferon plus ribavirin for patients with genotype 2 CHC based on RVR studies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Treatment with peginterferon plus daily low dose (800 mg) or weight-based ribavirin (800-1400 mg) for 24 to 48 weeks has achieved 70-93% sustained virologic response (SVR) rates in patients with genotype 2 or 3 chronic hepatitis C (CHC). Recently, a large randomized study has shown that patients with genotype 2 or 3 CHC have comparable SVR rates for those who received peginterferon for 24 or 48 weeks, and who received daily low dose (800 mg) or standard dose (1000-1200 mg) ribavirin. Therefore, the currently recommended treatment for these patients is 24 weeks of peginterferon plus low dose ribavirin. Because of the high response rates, several studies have shown that when these patients had rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV) RNA levels, at week 4 of peginterferon plus weight-based ribavirin, 12-16 weeks of treatment could have 82-94% SVR rates. However, treatment with peginterferon plus low dose ribavirin for 24 weeks showed significantly higher SVR rates than that for 16 weeks (85% vs. 79%) in these patients who achieved RVR. While studies showed concordant results in SVR rates for patients with genotype 3 CHC who received peginterferon plus low dose or weight-based ribavirin for 16 or 24 weeks, the SVR rates stratified by RVR showed great differences in patients with genotype 2 CHC who received such treatment. Currently, there are no studies on the direct comparison of low dose versus weight-based ribavirin, and of 16 to 24 weeks of treatment stratified by RVR for patients with genotype 2 CHC. We aimed to conduct a randomized trial to determine the optimal ribavirin dose and treatment duration of peginterferon plus ribavirin for patients with genotype 2 CHC based on RVR studies.

Study Type

Interventional

Enrollment (Actual)

880

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Douliou, Taiwan
        • National Taiwan University Hospital, Yun-Lin branch
      • Kaohsiung, Taiwan
        • Kaohsiung Medical University
      • Kaohsiung, Taiwan
        • Kaohsiung Municipal Hsiao-Kang Hospital
      • Pingtung, Taiwan
        • Paochien Hospital
      • Taichung, Taiwan
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
      • Taipei, Taiwan
        • Far Eastern Memorial Hospital
      • Taipei, Taiwan
        • Ren-Ai Branch, Taipei Municipal Hospital
      • Taipei, Taiwan
        • Buddhist Xindian Tzu Chi General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Treatment naïve
  • Age older than 18 years old
  • Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months
  • Detectable serum quantitative HCV-RNA (Cobas Taqman HCV Monitor v2.0, Roche Diagnostics) with dynamic range 25 ~ 391000000 IU/ml
  • HCV genotype 2 (Inno-LiPA HCV II, Innogenetics, Ghent, Belgium)
  • Serum alanine aminotransferase levels above the upper limit of normal with 6 months of enrollment
  • A liver biopsy consistent with the diagnosis of chronic hepatitis C

Exclusion Criteria:

  • Anemia (hemoglobin < 13 grams per deciliter for men and < 12 grams per deciliter for women)
  • Neutropenia (neutrophil count < 1,500 per cubic milliliter)
  • Thrombocytopenia (platelets < 90,000 per cubic milliliter)
  • Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
  • Chronic alcohol abuse (daily consumption > 20 grams per day)
  • Decompensated liver disease (Child-Pugh class B or C)
  • Serum creatinine level more than 1.5 times the upper limit of normal
  • Autoimmune liver disease
  • Neoplastic disease
  • An organ transplant
  • Immunosuppressive therapy
  • Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
  • Evidence of drug abuse
  • Unwilling to use contraception
  • Unwilling to sign informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Peg-IFN + WB RBV for 16 weeks
Weight-based ribavirin (1000-1200 mg/day) from weeks 1-16 in patients with RVR
Drug: Peg-IFN + WB RBV for 16 weeks
  1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-4
  2. Rapid virologic response (RVR) at week 4 of therapy: achieved
  3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 5-16
Other Names:
  • Pegasys plus Copegus
Active Comparator: Peg-IFN + LD RBV for 16 weeks
Weight-based ribavirin (1000-1200 mg/day) from weeks 1-6, and then low dose ribavirin (800 mg/day) from weeks 6-16 in patients with RVR
Drug: Peg-IFN + LD RBV for 16 weeks
  1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-6
  2. Rapid virologic response (RVR) at week 4 of therapy: achieved
  3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 800 mg/day from weeks 6-16
Other Names:
  • Pegasys plus Copegus
Active Comparator: Peg-IFN + WB RBV for 24 weeks
Weight-based ribavirin (1000-1200 mg/day) from weeks 1-24 in patients without RVR
Drug: Peg-IFN + WB RBV for 24 weeks
  1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-4
  2. Rapid virologic response (RVR) at week 4 of therapy: not achieved
  3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day from weeks 5-24
Other Names:
  • Pegasys plus Copegus
Active Comparator: Peg-IFN + WB RBV for 48 weeks
Weight-based ribavirin (1000-1200 mg/day) from weeks 1-48 in patients without RVR
Drug: Peg-IFN + WB RBV for 48 weeks
  1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-4
  2. Rapid virologic response (RVR) at week 4 of therapy: not achieved
  3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day from weeks 5-48
Other Names:
  • Pegasys plus Copegus
Active Comparator: Peg-IFN + LD RBV for 24 weeks
Low dose ribavirin (800 mg/day) from weeks 1-24 in patients with or without RVR
Drug: Peg-IFN + LD RBV for 24 weeks
  1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 800 mg/day from weeks 1-24
  2. Rapid virologic response (RVR) at week 4 of therapy: both achieved and not achieved
Other Names:
  • Pegasys plus Copegus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Sustained virologic response (SVR)
Time Frame: 1.5 year
1.5 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Histologic response (HR)
Time Frame: 1.5 year
1.5 year
Biochemical response (BR)
Time Frame: 1.5
1.5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Collaborators

National Science Council, Taiwan
Department of Health, Executive Yuan, R.O.C. (Taiwan)

Investigators

  • Principal Investigator: Chun-Jen Liu, MD, PhD, National Taiwan University Hospital
  • Principal Investigator: Chen-Hua Liu, MD, National Taiwan University Hospital
  • Principal Investigator: Wan-Long Chuang, MD, PhD, Kaohsiung Medical University
  • Principal Investigator: Pei-Jer Chen, MD, PhD, National Taiwan University Hospital
  • Principal Investigator: Sheng-Shun Yang, MD, Taichung Veterans General Hospital
  • Principal Investigator: Ding-Shinn Chen, MD, National Taiwan University Hospital
  • Principal Investigator: Chia-Yen Dai, MD, Ms, Kaohsiung Municipal Hsiao-Kang Hospital
  • Principal Investigator: Chang-Fu Chiu, MD, Paochien Hospital
  • Principal Investigator: Ming-Yang Lai, MD, PhD, National Taiwan University Hospital
  • Principal Investigator: Chih-Lin Lin, MD, Taipei City Hospital, Ren-Ai Branch
  • Principal Investigator: Ching-Sheng Hsu, MD, Buddhist Xindian Tzu Chi General Hospital
  • Principal Investigator: Chia-Chi Wang, MD, Buddhist Xindian Tzu Chi General Hospital
  • Principal Investigator: Tai-Chung Tseng, MD, Buddhist Xindian Tzu Chi General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

September 18, 2007

First Submitted That Met QC Criteria

September 18, 2007

First Posted (Estimate)

September 20, 2007

Study Record Updates

Last Update Posted (Estimate)

June 4, 2014

Last Update Submitted That Met QC Criteria

June 3, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200709014M

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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