A Randomized Trial of 24-Week Versus 48-Week Courses of Peginterferon Plus Ribavirin for HCV Genotype-6 Patients

Study Overview
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Brief Summary
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Patients with HCV genotype 6 infection who have a rapid virological response to treatment are randomised to either 24 or 48 weeks HCV treatment. Our hypothesis is that there is no important difference in effect between the two treatment effect.

Detailed Description
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High rate of infection of Hepatitis C Virus(HCV) Genotype 6 was recently confirmed in Southern China. Recent study implied chronic hepatitis C genotype 6 responds better to the 48-week treatment with pegylated interferon and ribavirin than genotype 1. Approximately 75.7% obtain sustained virological response (HCV RNA undetectable 24 weeks after treatment) to this approach. However, the treatment is associated with many and sometimes serious side effects. In addition, the treatment is costly also in economical terms. Shorter treatment for chronic hepatitis C genotype 6 is necessary to be assessed. In this randomised,open label,multicenter phase 3 trial with active controls patients are treated with pegylated interferon alfa 2a (180ug/week)and ribavirin(800-1200mg based on weight)for 4 weeks. Those who are HCV RNA negative at week 4 (<50 IU; Cobas Amplicor Monitor Test, Roche Diagnostic) are defined as rapid virological responders and randomised to either an additional 20 or 44 weeks combination treatment. Patients who are HCV RNA positive are all treated for 44 more weeks. The endpoint is sustained virological response defined as undetectable HCV RNA 24 weeks after end of treatment. Our hypothesis is that there is no important difference in the effect in the two groups. This is a non-inferiority trial. The smallest difference considered to be clinically important is 15%. Thus to state non-inferiority the 95% confidence interval of the observed difference between the groups shall not overlap 10%. Both intention to treat and and per protocol analyses will be published. Conclusion will be conservative and based on the analysis who detect the biggest difference.

Official Title
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A Randomized Trial of 24-Week Versus 48-Week Courses of Peginterferon Plus

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Peginterferon alfa2a
* Drug: Ribavirin
* Drug: Peginterferon alfa2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV RNA is positive Genotype 6 Treatment naive Raised ALT Exclusion Criteria: Active substance abuse Poorly controlled psychiatric disease HBsAg positive Anti-HIV positive Suffering from other significant concurrent medical conditions including chronic liver diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: 24-Week treatment group<br>Genotype 6 chronic hepatitis C patients with rapid virological response(undetectable HCV RNA at weeks 4) in this group will be treated with Peginterferon alfa-2a plus ribavirin for an additional 20 weeks | Drug: Peginterferon alfa2a<br>* patients receive a dose of 180 µg of PEGASYS once a week for 24 weeks<br>Drug: Ribavirin<br>* patients receive a dose 800 to 1200 mg of ribavirin once a day(according to weight) for 24 weeks<br>|
| Active Comparator: 48-Week treatment group<br>Genotype 6 chronic hepatitis C patients with rapid virological response(undetectable HCV RNA at weeks 4) in this group will be treated with Peginterferon alfa-2a plus ribavirin for an additional 44 weeks | Drug: Peginterferon alfa2a<br>* patients receive a dose of 180 µg of PEGASYS once a week for 48 weeks<br>Drug: Ribavirin<br>* patients receive a dose 800 to 1200 mg of ribavirin once a day(according to weight) for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response (SVR) | Undetectable HCVRNA in serum(<15IU/ml) 24 weeks after the end of treatment | 24 weeks after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in health related quality as measured by short from 36 (SF-36) from baseline to 24 weeks after the end of treatment |  | 24 weeks after the end of treatment | 
| Sick leave in patients treated for 24 or 48 weeks treatment |  | 48 weeks |