Early Prediction of Successful Treatment for Chronic Hepatitis C Virus Infection in Taiwan

NCT ID: NCT00543244

Last Updated: 2008-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2006-01-31

Study Completion Date

2008-12-31

Brief Summary

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Hepatitis C virus (HCV) infection is a global health problem, which may lead to chronic hepatitis, cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). Recently, treatment with peginterferon alfa plus ribavirin has become the standard of care for patients with chronic hepatitis C. While genotype 2 patients can have higher sustained virologic response (SVR) rates to 80-90%, genotype 1 patients generally have low SVR rates of only 40-50%. In contrast, genotype 1 Taiwanese patients have superior SVR rates than those in Western countries. Despite the overall improved response to this combination therapy, more than 75% of patients suffer from treatment-related adverse events and the costs remain high, which make individualized therapy of paramount importance to maximize treatment response and minimize adverse events.

HCV viral kinetics with interferon-based therapies have been studied recently to evaluate patient responses. Early viral kinetics shown to have favorable SVR rates, which make shorter treatment duration possible. However, different viral kinetics were found through ethnicity. Recently, a pilot study to evaluate the viral kinetics of 6 Taiwanese patients with HCV infection who received peginterferon alfa plus ribavirin therapy has shown superior early viral kinetics to those in Caucasian patients. Based on the favorable SVR rates in treating Taiwanese patients with chronic hepatitis C, the investigators aimed to conduct a large confirmatory study to evaluate the viral kinetics and try to define the optimal treatment for these patients.

Detailed Description

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Hepatitis C virus (HCV) infection is a global health problem, which may lead to chronic hepatitis, cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). \[1,2\] Recently, treatment with peginterferon alfa plus ribavirin has become the standard of care for patients with chronic hepatitis C. While genotype 2 patients can have higher sustained virologic response (SVR) rates to 80-90%, genotype 1 patients generally have low SVR rates of only 40-50%. \[3-5\] In contrast, genotype 1 Taiwanese patients have superior SVR rates that those in Western countries. \[6,7\] Despite the overall improved response to this combination therapy, more than 75% of patients suffer from treatment-related adverse events and the costs remain high, \[8,9\] which make individualized therapy of paramount importance to maximize treatment response and minimize adverse events.

HCV viral kinetics with interferon-based therapies have been studied recently to evaluate patient responses. \[10-14\] Early viral kinetics shown to have favorable SVR rates, which make shorter treatment duration possible. \[15-18\] However, different viral kinetics were found through ethnicity. \[19-23\] Recently, a pilot study to evaluate the viral kinetics of 6 Taiwanese patients with HCV infection who received peginterferon alfa plus ribavirin therapy has shown superior early viral kinetics to those in Caucasian patients. \[24\] Based on the favorable SVR rates in treating Taiwanese patients with chronic hepatitis C, the investigators aimed to conduct a large confirmatory study to evaluate the viral kinetics and try to define the optimal treatment for these patients.

Conditions

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Chronic Hepatitis C

Keywords

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Chronic hepatitis C Pegylated interferon Ribavirin Virokinetics

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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1

Patients with chronic hepatitis C who receive pegylated interferon plus ribavirin for 24 weeks (genotype 1 or 2) and for 48 weeks (genotype 1)

Pegylated interferon alfa and ribavirin

Intervention Type DRUG

Pegylated interferon alfa-2a 180 ug/week or pegylated interferon alfa-2b 1.5 ug/kg/week Ribavrin 800-1200 mg/day (genotype 1: \< 75 kg 1000 mg/day, \>=75 kg 1200 mg/day; genotype 2: 800 mg/day)

HCV genotype: baseline (Day 0) HCV RNA (real time PCR test): baseline (Day 0), Day 1 (4,8,12 hours after pegylated interferon + ribavirin), Day 2 (24,36 hours), Day 3(48 hours), Day 4 (72 hours), Day 5 (96 hours), Week 2,4,6,8,12,16,20,24, and 28,32,36,40,44,48,72 (for genotype 1 with 48 weeks of treatment), and 48 (for genotype 1 or 2 with 24 weeks of treatment)

Interventions

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Pegylated interferon alfa and ribavirin

Pegylated interferon alfa-2a 180 ug/week or pegylated interferon alfa-2b 1.5 ug/kg/week Ribavrin 800-1200 mg/day (genotype 1: \< 75 kg 1000 mg/day, \>=75 kg 1200 mg/day; genotype 2: 800 mg/day)

HCV genotype: baseline (Day 0) HCV RNA (real time PCR test): baseline (Day 0), Day 1 (4,8,12 hours after pegylated interferon + ribavirin), Day 2 (24,36 hours), Day 3(48 hours), Day 4 (72 hours), Day 5 (96 hours), Week 2,4,6,8,12,16,20,24, and 28,32,36,40,44,48,72 (for genotype 1 with 48 weeks of treatment), and 48 (for genotype 1 or 2 with 24 weeks of treatment)

Intervention Type DRUG

Other Intervention Names

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Pegasys plus Robatrol Peg-Intron plus Rebetol

Eligibility Criteria

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Inclusion Criteria

* Treatment naïve
* Over 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
* 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
* Unwilling to receive serial blood sampling during the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Science and Technology Council, Taiwan

OTHER_GOV

Sponsor Role collaborator

National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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National Taiwan University Hospital

Principal Investigators

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Jia-Horng Kao, MD, PhD

Role: STUDY_CHAIR

National Taiwan University Hospital

Avidan Uriel Neumann, PhD

Role: PRINCIPAL_INVESTIGATOR

Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel

Chen-Hua Liu, MD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

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Faculty of Life Sciences, Bar-Ilan University

Ramat Gan, , Israel

Site Status RECRUITING

National Taiwan University Hospital, Yun-Lin Branch

Douliu, , Taiwan

Site Status RECRUITING

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Buddhist Tzu Chi General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Far Eastern Memorial Hospital

Taipei, , Taiwan

Site Status RECRUITING

Ren-Ai Branch, Taipei Municipal Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Israel Taiwan

Central Contacts

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Jia-Horng Kao, MD, PhD

Role: CONTACT

Phone: 886-2-23123456

Email: [email protected]

Avidan Uriel Neumann, PhD

Role: CONTACT

Phone: 972-3-531-7970

Email: [email protected]

References

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Chen DS, Kuo GC, Sung JL, Lai MY, Sheu JC, Chen PJ, Yang PM, Hsu HM, Chang MH, Chen CJ, et al. Hepatitis C virus infection in an area hyperendemic for hepatitis B and chronic liver disease: the Taiwan experience. J Infect Dis. 1990 Oct;162(4):817-22. doi: 10.1093/infdis/162.4.817.

Reference Type BACKGROUND
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Lai MY. Combined interferon and ribavirin therapy for chronic hepatitis C in Taiwan. Intervirology. 2006;49(1-2):91-5. doi: 10.1159/000087269.

Reference Type BACKGROUND
PMID: 16166795 (View on PubMed)

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.

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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.

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PMID: 12407599 (View on PubMed)

Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998 Oct 2;282(5386):103-7. doi: 10.1126/science.282.5386.103.

Reference Type BACKGROUND
PMID: 9756471 (View on PubMed)

Lee WM, Reddy KR, Tong MJ, Black M, van Leeuwen DJ, Hollinger FB, Mullen KD, Pimstone N, Albert D, Gardner S. Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group. Hepatology. 1998 Nov;28(5):1411-5. doi: 10.1002/hep.510280533.

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Orito E, Mizokami M, Suzuki K, Ohba K, Ohno T, Mori M, Hayashi K, Kato K, Iino S, Lau JY. Loss of serum HCV RNA at week 4 of interferon-alpha therapy is associated with more favorable long-term response in patients with chronic hepatitis C. J Med Virol. 1995 Jun;46(2):109-15. doi: 10.1002/jmv.1890460205.

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PMID: 7636496 (View on PubMed)

Colombatto P, Civitano L, Oliveri F, Coco B, Ciccorossi P, Flichman D, Campa M, Bonino F, Brunetto MR. Sustained response to interferon-ribavirin combination therapy predicted by a model of hepatitis C virus dynamics using both HCV RNA and alanine aminotransferase. Antivir Ther. 2003 Dec;8(6):519-30.

Reference Type BACKGROUND
PMID: 14760885 (View on PubMed)

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Jessner W, Stauber R, Hackl F, Datz C, Watkins-Riedel T, Hofer H, Gangl A, Kessler H, Ferenci P. Early viral kinetics on treatment with pegylated interferon-alpha-2a in chronic hepatitis C virus genotype 1 infection. J Viral Hepat. 2003 Jan;10(1):37-42. doi: 10.1046/j.1365-2893.2003.00396.x.

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McHutchison JG, Poynard T, Pianko S, Gordon SC, Reid AE, Dienstag J, Morgan T, Yao R, Albrecht J. The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C. The International Hepatitis Interventional Therapy Group. Gastroenterology. 2000 Nov;119(5):1317-23. doi: 10.1053/gast.2000.19289.

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Other Identifiers

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200709053R

Identifier Type: -

Identifier Source: org_study_id