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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Peginterferon alfa2a; Drug: Ribavirin; Drug: Peginterferon alfa2a; Drug: Ribavirin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • The Eighth People's Hospital of Guangzhou
    • Guangzhou, Guangdong, China, 510630
      • The Third Affliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • Panyu People's Hospital
    • Zhongshan, Guangdong, China
      • Zhongshan Second People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 24-Week treatment group; 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; patients receive a dose of 180 µg of PEGASYS once a week for 24 weeks; Drug: Ribavirin; patients receive a dose 800 to 1200 mg of ribavirin once a day(according to weight) for 24 weeks; Drug: Peginterferon alfa2a; patients receive a dose of 180 µg of PEGASYS once a week for 48 weeks; Drug: Ribavirin; patients receive a dose 800 to 1200 mg of ribavirin once a day(according to weight) for 48 weeks
Active Comparator: 48-Week treatment group; 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; patients receive a dose of 180 µg of PEGASYS once a week for 24 weeks; Drug: Ribavirin; patients receive a dose 800 to 1200 mg of ribavirin once a day(according to weight) for 24 weeks; Drug: Peginterferon alfa2a; patients receive a dose of 180 µg of PEGASYS once a week for 48 weeks; Drug: Ribavirin; patients receive a dose 800 to 1200 mg of ribavirin once a day(according to weight) for 48 weeks

What is the study measuring?

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	Time Frame
Sick leave in patients treated for 24 or 48 weeks treatment	48 weeks
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

Collaborators and Investigators

• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University
• Investigators: Study Chair: Gao Zhiliang, Doctor, The Third Affliated Hospital of Sun Yat-sen University; Study Director: Zhao Zhixin, Doctor, The Third Affliated Hospital of Sun Yat-sen University; Principal Investigator: Zhang Xiaohong, Doctor, The Third Affliated Hospital of Sun Yat-sen University; Principal Investigator: Xu Min, Doctor, The Eighth People's Hospital of Guangzhou; Principal Investigator: Wei min, Doctor, Zhongshan Second People's Hospital; Principal Investigator: Huang mingshou, Bachelor, Panyu People's Hospital

Publications and helpful links

General Publications

• Cai Q, Zhang X, Lin C, Shao X, Guan Y, Deng H, Wei M, Huang M, Ren Z, Lu L, Mei Y, Xu M, Zhu J, Shi H, Lin G, Liu Y, Hu F, Luo Q, Lan Y, Guo F, Zhao Z, Gao Z. 24 versus 48 Weeks of Peginterferon Plus Ribavirin in Hepatitis C Virus Genotype 6 Chronically Infected Patients with a Rapid Virological Response: A Non-Inferiority Randomized Controlled Trial. PLoS One. 2015 Oct 28;10(10):e0140853. doi: 10.1371/journal.pone.0140853. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: December 20, 2010
• First Submitted That Met QC Criteria: December 20, 2010
• First Posted (Estimate): December 21, 2010

Study Record Updates

• Last Update Posted (Estimate): November 18, 2014
• Last Update Submitted That Met QC Criteria: November 14, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Immunologic Factors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: TAH115G6HCV