Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for HCV Genotype 1-infected Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00495131

Recruitment Status : Completed

First Posted : July 2, 2007

Results First Posted : September 7, 2009

Last Update Posted : September 10, 2009

Sponsor:

Collaborator:

National Science Council, Taiwan

Information provided by:

National Taiwan University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis C, Chronic	Drug: Pegylated interferon alfa-2a plus ribavirin	Phase 4

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	308 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus Genotype 1-infected Patients in Taiwan
Study Start Date :	June 2006
Actual Primary Completion Date :	June 2008
Actual Study Completion Date :	July 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Interferon Ribavirin Interferon Alfa-2a Interferon Alfa-2b Peginterferon Alfa-2a

U.S. FDA Resources

Arms and Interventions

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	Drug: Pegylated interferon alfa-2a plus ribavirin 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 Name: Pegasys plus Robatrol
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	Drug: Pegylated interferon alfa-2a plus ribavirin 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 Name: Pegasys plus Robatrol

Outcome Measures

Primary Outcome Measures :

Sustained Virologic Response [ Time Frame: 18 months ]
Undetectable HCV RNA 6 months off therapy
Sustained Biochemical Response [ Time Frame: 18 months ]
Sustained biochemical response (SBR): alanine aminotransferase (ALT) normalization

Secondary Outcome Measures :

Treatment-related Withdrawal Rate [ Time Frame: 18 months ]
Treatment-related withdrawal rate: patients who prematurely discontinued treatment due to treatment-related adverse events
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

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00495131

Locations

Layout table for location information

Taiwan
National Taiwan University Hospital, Yun-Lin Branch
Douliou, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Buddhist Tzu Chi General Hospital
Taipei, Taiwan
Far Eastern Memorial Hospital
Taipei, Taiwan
Ren-Ai Branch, Taipei Municipal Hospital
Taipei, Taiwan

Sponsors and Collaborators

National Taiwan University Hospital

National Science Council, Taiwan

Investigators

Layout table for investigator information

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:	Chun-Jen Liu, MD, PhD	National Taiwan University Hospital
Principal Investigator:	Chen-Hua Liu, MD	National Taiwan University Hospital
Principal Investigator:	Shih-Jer Hsu, MD	National Taiwan University Hosptial, Yun-Lin Branch
Principal Investigator:	Chih-Lin Lin, MD	Ren-Ai Branch, Taipei City Hospital
Principal Investigator:	Cheng-Chao Liang, MD	Far Eastern Memorial Hospital
Principal Investigator:	Ching-Sheng Hsu, MD	Buddhist Tzu Chi General Hospital
Principal Investigator:	Sheng-Shun Yang, MD	Taichung Veterans General Hospital

More Information

Publications:

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.

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.

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.

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, Frydén A, Braconier JH, Sönnerborg 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.

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. Review.

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.

Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger 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.

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.

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. Review.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Dr. Jia-Horng Kao, National Taiwan University Hospital
ClinicalTrials.gov Identifier:	NCT00495131
Other Study ID Numbers:	200705080M
First Posted:	July 2, 2007 Key Record Dates
Results First Posted:	September 7, 2009
Last Update Posted:	September 10, 2009
Last Verified:	September 2009

Keywords provided by National Taiwan University Hospital:


Chronic hepatitis C Genotype 1 Interferon Ribavirin

Additional relevant MeSH terms:

Layout table for MeSH terms

Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Hepatitis, Chronic	Interferons Ribavirin Interferon-alpha Interferon alpha-2 Peginterferon alfa-2a Antineoplastic Agents Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs

To Top