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

NCT ID: NCT00532701

Last Updated: 2014-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 880 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2014-03-31

Brief Summary

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.

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.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Peg-IFN + WB RBV for 24 weeks

Weight-based ribavirin (1000-1200 mg/day) from weeks 1-24 in patients without RVR

Group Type: ACTIVE_COMPARATOR

Peg-IFN + WB RBV for 24 weeks

Intervention Type: DRUG

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

Peg-IFN + WB RBV for 48 weeks

Weight-based ribavirin (1000-1200 mg/day) from weeks 1-48 in patients without RVR

Group Type: ACTIVE_COMPARATOR

Peg-IFN + WB RBV for 48 weeks

Intervention Type: DRUG

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

Peg-IFN + LD RBV for 24 weeks

Low dose ribavirin (800 mg/day) from weeks 1-24 in patients with or without RVR

Group Type: ACTIVE_COMPARATOR

Peg-IFN + LD RBV for 24 weeks

Intervention Type: DRUG

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

Peg-IFN + WB RBV for 16 weeks

Weight-based ribavirin (1000-1200 mg/day) from weeks 1-16 in patients with RVR

Group Type: ACTIVE_COMPARATOR

Peg-IFN + WB RBV for 16 weeks

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Peg-IFN + LD RBV for 16 weeks

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Pegasys plus Copegus; Pegasys plus Copegus; Pegasys plus Copegus; Pegasys plus Copegus; Pegasys plus Copegus

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Science and Technology Council, Taiwan

OTHER_GOV

Sponsor Role: collaborator

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

OTHER_GOV

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jia-Horng Kao, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Ding-Shinn Chen, MD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Ming-Yang Lai, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Pei-Jer Chen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Chun-Jen Liu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Chen-Hua Liu, MD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Shih-Jer Hsu, MD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital, Yun-Lin Branch

Chih-Lin Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Taipei City Hospital, Ren-Ai Branch

Cheng-Chao Liang, MD

Role: PRINCIPAL_INVESTIGATOR

Far Eastern Memorial Hospital

Ching-Sheng Hsu, MD

Role: PRINCIPAL_INVESTIGATOR

Buddhist Xindian Tzu Chi General Hospital

Sheng-Shun Yang, MD

Role: PRINCIPAL_INVESTIGATOR

Taichung Veterans General Hospital

Chia-Chi Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Buddhist Xindian Tzu Chi General Hospital

Tai-Chung Tseng, MD

Role: PRINCIPAL_INVESTIGATOR

Buddhist Xindian Tzu Chi General Hospital

Ming-Lung Yu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Medical University

Wan-Long Chuang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Medical University

Chia-Yen Dai, MD, Ms

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Municipal Hsiao-Kang Hospital

Jee-Fu Huang, MD

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Municipal Hsiao-Kang Hospital

Chang-Fu Chiu, MD

Role: PRINCIPAL_INVESTIGATOR

Paochien Hospital

Locations

National Taiwan University Hospital, Yun-Lin Branch

Douliu, , Taiwan

Kaohsiung Medical University

Kaohsiung City, , Taiwan

Kaohsiung Municipal Hsiao-Kang Hospital

Kaohsiung City, , Taiwan

Paochien Hospital

Pingtung City, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Buddhist Xindian Tzu Chi General Hospital

Taipei, , Taiwan

Far Eastern Memorial Hospital

Taipei, , Taiwan

Ren-Ai Branch, Taipei Municipal Hospital

Taipei, , Taiwan

Countries

Taiwan

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Other Identifiers

200709014M

Identifier Type: -

Identifier Source: org_study_id