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

Information source: National Taiwan University Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hepatitis C, Chronic

Intervention: Pegylated interferon alfa-2a plus ribavirin (Drug); Pegylated interferon alfa-2a plus ribavirin (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: National Taiwan University Hospital

Official(s) and/or principal investigator(s):
Jia-Horng Kao, MD, PhD, Study Chair, Affiliation: National Taiwan University Hospital
Ding-Shinn Chen, MD, Study Director, Affiliation: National Taiwan University Hospital
Ming-Yang Lai, MD, PhD, Study Director, Affiliation: National Taiwan University Hospital
Pei-Jer Chen, MD, PhD, Study Director, Affiliation: National Taiwan University Hospital
Chun-Jen Liu, MD, PhD, Principal Investigator, Affiliation: National Taiwan University Hospital
Chen-Hua Liu, MD, Principal Investigator, Affiliation: National Taiwan University Hospital
Shih-Jer Hsu, MD, Principal Investigator, Affiliation: National Taiwan University Hosptial, Yun-Lin Branch
Chih-Lin Lin, MD, Principal Investigator, Affiliation: Ren-Ai Branch, Taipei City Hospital
Cheng-Chao Liang, MD, Principal Investigator, Affiliation: Far Eastern Memorial Hospital
Ching-Sheng Hsu, MD, Principal Investigator, Affiliation: Buddhist Tzu Chi General Hospital
Sheng-Shun Yang, MD, Principal Investigator, Affiliation: Taichung Veterans General Hospital

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Sustained Virologic Response

Sustained Biochemical Response

Secondary outcome:

Treatment-related Withdrawal Rate

Histologic Response

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan

Taichung Veterans General Hospital, Taichung, Taiwan

Buddhist Tzu Chi General Hospital, Taipei, Taiwan

Far Eastern Memorial Hospital, Taipei, Taiwan

National Taiwan University Hospital, Taipei 100, Taiwan

Ren-Ai Branch, Taipei Municipal Hospital, Taipei, Taiwan

Additional Information

Related 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.

Starting date: June 2006
Last updated: September 7, 2009

Page last updated: August 23, 2015

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