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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Peg-IFN + WB RBV for 16 weeks
* Drug: Peg-IFN + LD RBV for 16 weeks
* Drug: Peg-IFN + WB RBV for 24 weeks
* Drug: Peg-IFN + WB RBV for 48 weeks
* Drug: Peg-IFN + LD RBV for 24 weeks


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virologic response (SVR) |  | 1.5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologic response (HR) |  | 1.5 year | 
| Biochemical response (BR) |  | 1.5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genotype, Chronic hepatitis C, Interferon, Ribavirin, Genotype 2, Peginterferon