- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00495131
Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for HCV Genotype 1-infected Patients
September 7, 2009 updated by: National Taiwan University Hospital
Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus Genotype 1-infected Patients in Taiwan
Chronic hepatitis C virus (HCV) infection is prevalent in the world, affecting 3% of the world's population.
The current standard of therapy is pegylated interferon and ribavirin, reaching 54-63% of successful rates.
In patients with HCV genotype 1 infection, a 48 week course of combination therapy has achieved a higher successful rate that a 24 weeks course of therapy.
However, several studies in Taiwan have shown that a 24 week course of therapy has comparable or even better response to a 48 week course of therapy in Western countries.
Therefore, whether a 48 week course of therapy can achieve a higher response to a 24 week course of therapy in Taiwanese patients with genotype 1 HCV infection remains unclear.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Combination therapy with interferon alfa (IFN-α) plus ribavirin for 24 to 48 weeks produces sustained virologic response (SVR) rate in approximately 31-47% of treatment naïve patients with chronic hepatitis C.(1-5) Patients with genotype 1 virus infection are less likely to have SVR that those with other genotypes infection, and therefore, patients infected with hepatitis C virus (HCV) genotype 1 should receive treatment for 48 weeks.(6)
Recently, combination therapy with pegylated interferon alfa (pegylated IFN-α) plus ribavirin produces higher SVR rates (54-56%) than that with IFN-α plus ribavirin.(7,8)
Furthermore, a large trial assessing the effect and duration of pegylated IFN-α plus ribavirin showed that the overall SVR rate was 63%.
Among patients with genotype 1 HCV infection, standard dose ribavirin (1000 to 1200 mg per day) and 48 weeks of treatment were significantly more effective than low dose ribavirin (800 mg per day) or 24 weeks of treatment.(9)
The SVR rate was 51% for genotype 1 patients receiving pegylated IFN-α plus standard dose ribavirin for 48 weeks, whereas only 29% and 41% for those receiving pegylated IFN-α plus low dose ribavirin and standard dose ribavirin for 24 weeks, respectively.
Based on these lines of evidence, 48 weeks of therapy with pegylated IFN-α (pegylated IFN-α 2a 180 μg or pegylated IFN-α 2b 1.5 μg per kilogram body weight weekly) plus ribavirin (1000 to 1200 mg per day) is recommended to treat patients with HCV genotype 1 infection.(10)
In Taiwan, a multicenter study showed that a 6 month course treatment with pegylated IFN-α plus standard dose ribavirin had a comparable SVR rate to that with IFN-α plus standard dose ribavirin (67.1% versus 63.6%) in patients with chronic hepatitis C. Subgroup analysis showed that treatment with pegylated IFN-α plus standard dose ribavirin had a significantly higher SVR rate to that with IFN-α plus standard dose ribavirin (65.8% versus 41.0%) in patients with genotype 1 HCV infection.(11)
Recently, a pilot study comparing 24 and 48 weeks of pegylated IFN-α plus standard dose ribavirin in patients with genotype 1 HCV infection showed that 48 weeks of treatment is more efficacious that 24 weeks of treatment (SVR rate: 80.0% versus 48.9%).(12)
However, much difference of SVR rates occurred in these two studies, making optimal therapy in Taiwanese patients infected with genotype 1 HCV difficult to be determined.
In the study, we aim to investigate in a large cohort whether 48 weeks treatment with pegylated IFN-α plus standard dose ribavirin is more efficacious than 24 weeks treatment in patients with genotype 1 HCV infection.
Study Type
Interventional
Enrollment (Actual)
308
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
-
-
-
Douliou, Taiwan
- National Taiwan University Hospital, Yun-Lin Branch
-
Taichung, Taiwan
- Taichung Veterans General Hospital
-
Taipei, Taiwan, 100
- National Taiwan University Hospital
-
Taipei, Taiwan
- Far Eastern Memorial Hospital
-
Taipei, Taiwan
- Buddhist Tzu Chi General Hospital
-
Taipei, Taiwan
- Ren-Ai Branch, Taipei Municipal 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 18 and 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 Amplicor HCV Monitor v2.0, Roche Molecular Systems, Pleasanton, CA) with dynamic range 600~<500,000 IU/ml
- HCV genotype 1 (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 gram per deciliter for men and < 12 gram per deciliter for women)
- Neutropenia (neutrophil count <1,500 per cubic milliliter)
- Thrombocytopenia (platelet <90,000 per cubic milliliter)
- Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
- Chronic alcohol abuse (daily consumption > 20 gram 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 have contraception
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: Peginterfron and ribavirin (24 weeks)
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 24 weeks
|
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 24 weeks
Other Names:
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 48 weeks
Other Names:
|
Active Comparator: Peginterferon and ribavirin (48 weeks)
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 48 weeks
|
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 24 weeks
Other Names:
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 48 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sustained Virologic Response
Time Frame: 18 months
|
Undetectable HCV RNA 6 months off therapy
|
18 months
|
Sustained Biochemical Response
Time Frame: 18 months
|
Sustained biochemical response (SBR): alanine aminotransferase (ALT) normalization
|
18 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-related Withdrawal Rate
Time Frame: 18 months
|
Treatment-related withdrawal rate: patients who prematurely discontinued treatment due to treatment-related adverse events
|
18 months
|
Histologic Response
Time Frame: 18 months
|
Histologic response: improvement of at least 2 grade of scores by Ishak liver histologic classification by end of follow up liver biopsy to baseline liver biopsy
|
18 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Chun-Jen Liu, MD, PhD, National Taiwan University Hospital
- Principal Investigator: Chen-Hua Liu, MD, National Taiwan University Hospital
- Study Chair: Jia-Horng Kao, MD, PhD, National Taiwan University Hospital
- Study Director: Ding-Shinn Chen, MD, National Taiwan University Hospital
- Study Director: Ming-Yang Lai, MD, PhD, National Taiwan University Hospital
- Study Director: Pei-Jer Chen, MD, PhD, National Taiwan University Hospital
- Principal Investigator: Sheng-Shun Yang, MD, Taichung Veterans 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
- EASL International Consensus Conference on Hepatitis C. Paris, 26-28, February 1999, Consensus Statement. European Association for the Study of the Liver. J Hepatol. 1999 May;30(5):956-61. No abstract available.
- McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998 Nov 19;339(21):1485-92. doi: 10.1056/NEJM199811193392101.
- Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht J. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. 1998 Oct 31;352(9138):1426-32. doi: 10.1016/s0140-6736(98)07124-4.
- Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. doi: 10.1016/s0140-6736(01)06102-5.
- Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. doi: 10.1056/NEJMoa020047.
- Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55. doi: 10.7326/0003-4819-140-5-200403020-00010.
- Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW, Chu JS, Chen DS. Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology. 1996 Nov;111(5):1307-12. doi: 10.1053/gast.1996.v111.pm8898645.
- Chemello L, Cavalletto L, Bernardinello E, Guido M, Pontisso P, Alberti A. The effect of interferon alfa and ribavirin combination therapy in naive patients with chronic hepatitis C. J Hepatol. 1995;23 Suppl 2:8-12.
- Reichard O, Norkrans G, Fryden A, Braconier JH, Sonnerborg A, Weiland O. Randomised, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. The Swedish Study Group. Lancet. 1998 Jan 10;351(9096):83-7. doi: 10.1016/s0140-6736(97)06088-1.
- National Institutes of Health. National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C: 2002--June 10-12, 2002. Hepatology. 2002 Nov;36(5 Suppl 1):S3-20. doi: 10.1053/jhep.2002.37117. No abstract available.
- Lee SD, Yu ML, Cheng PN, Lai MY, Chao YC, Hwang SJ, Chang WY, Chang TT, Hsieh TY, Liu CJ, Chen DS. Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan. J Viral Hepat. 2005 May;12(3):283-91. doi: 10.1111/j.1365-2893.2005.00590.x.
- Yu ML, Dai CY, Lin ZY, Lee LP, Hou NJ, Hsieh MY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. A randomized trial of 24- vs. 48-week courses of PEG interferon alpha-2b plus ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in Taiwan. Liver Int. 2006 Feb;26(1):73-81. doi: 10.1111/j.1478-3231.2005.01196.x.
- Liu CH, Liu CJ, Lin CL, Liang CC, Hsu SJ, Yang SS, Hsu CS, Tseng TC, Wang CC, Lai MY, Chen JH, Chen PJ, Chen DS, Kao JH. Pegylated interferon-alpha-2a plus ribavirin for treatment-naive Asian patients with hepatitis C virus genotype 1 infection: a multicenter, randomized controlled trial. Clin Infect Dis. 2008 Nov 15;47(10):1260-9. doi: 10.1086/592579.
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
June 1, 2006
Primary Completion (Actual)
June 1, 2008
Study Completion (Actual)
July 1, 2008
Study Registration Dates
First Submitted
June 29, 2007
First Submitted That Met QC Criteria
June 29, 2007
First Posted (Estimate)
July 2, 2007
Study Record Updates
Last Update Posted (Estimate)
September 10, 2009
Last Update Submitted That Met QC Criteria
September 7, 2009
Last Verified
September 1, 2009
More Information
Terms related to this study
Keywords
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
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Hepatitis
- Hepatitis A
- Hepatitis C
- Hepatitis C, Chronic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Interferon-alpha
- Ribavirin
- Peginterferon alfa-2a
- Interferon alpha-2
Other Study ID Numbers
- 200705080M
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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