Peginterferon Alfa-2a and Ribavirin for Genotype 2 Chronic Hepatitis C: Duration and Ribavirin Dose Stratified by RVR

Condition(s) targeted: Chronic Hepatitis C

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

Phase: Phase 4

Status: Recruiting

Sponsored by: National Taiwan University Hospital

Official(s) and/or principal investigator(s):
Jia-Horng Kao, MD, PhD, Principal Investigator, Affiliation: National Taiwan University Hospital
Ding-Shinn Chen, MD, Principal Investigator, Affiliation: National Taiwan University Hospital
Ming-Yang Lai, MD, PhD, Principal Investigator, Affiliation: National Taiwan University Hospital
Pei-Jer Chen, MD, PhD, Principal Investigator, 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 Hospital, Yun-Lin Branch
Chih-Lin Lin, MD, Principal Investigator, Affiliation: Taipei City Hospital, Ren-Ai Branch
Cheng-Chao Liang, MD, Principal Investigator, Affiliation: Far Eastern Memorial Hospital
Ching-Sheng Hsu, MD, Principal Investigator, Affiliation: Buddhist Xindian Tzu Chi General Hospital
Sheng-Shun Yang, MD, Principal Investigator, Affiliation: Taichung Veterans General Hospital
Chia-Chi Wang, MD, Principal Investigator, Affiliation: Buddhist Xindian Tzu Chi General Hospital
Tai-Chung Tseng, MD, Principal Investigator, Affiliation: Buddhist Xindian Tzu Chi General Hospital
Ming-Lung Yu, MD, PhD, Principal Investigator, Affiliation: Kaohsiung Medical University
Wan-Long Chuang, MD, PhD, Principal Investigator, Affiliation: Kaohsiung Medical University
Chia-Yen Dai, MD, Ms, Principal Investigator, Affiliation: Kaohsiung Municipal Hsiao-Kang Hospital
Jee-Fu Huang, MD, Principal Investigator, Affiliation: Kaohsiung Municipal Hsiao-Kang Hospital
Chang-Fu Chiu, MD, Principal Investigator, Affiliation: Paochien Hospital

Overall contact:
Chen-Hua Liu, MD, Phone: +886-2-23123456, Ext: 3572, Email: jacque_liu@mail2000.com.tw

Treatment with peginterferon plus daily low dose (800 mg) or weight-based ribavirin (800-1400 mg) for 24 to 48 weeks has achieved 70-93% sustained virologic response (SVR) rates in patients with genotype 2 or 3 chronic hepatitis C (CHC). Recently, a large randomized study has shown that patients with genotype 2 or 3 CHC have comparable SVR rates for those who received peginterferon for 24 or 48 weeks, and who received daily low dose (800 mg) or standard dose (1000-1200 mg) ribavirin. Therefore, the currently recommended treatment for these patients is 24 weeks of peginterferon plus low dose ribavirin. Because of the high response rates, several studies have shown that when these patients had rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, at week 4 of peginterferon plus weight-based ribavirin, 12-16 weeks of treatment could have 82-94% SVR rates. However, treatment with peginterferon plus low dose ribavirin for 24 weeks showed significantly higher SVR rates than that for 16 weeks (85% versus 79%) in these patients who achieved RVR. While studies showed concordant results in SVR rates for patients with genotype 3 CHC who received peginterferon plus low dose or weight-based ribavirin for 16 or 24 weeks, the SVR rates stratified by RVR showed great differences in patients with genotype 2 CHC who received such treatment. Currently, there are no studies on the direct comparison of low dose versus weight-based ribavirin, and of 16 to 24 weeks of treatment stratified by RVR for patients with genotype 2 CHC. The investigators aimed to conduct a randomized trial to determine the optimal ribavirin dose and treatment duration of peginterferon plus ribavirin for patients with genotype 2 CHC based on RVR studies.

Official title: Peginterferon Alfa-2a Plus Ribavirin in Patients With Genotype 2 Chronic Hepatitis C: A Randomized Study of Treatment Duration and Ribavirin Dose Stratified by Rapid Virologic Response

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

Primary outcome: Sustained virologic response (SVR)

Secondary outcome:

Histologic response (HR)

Biochemical response (BR)

Detailed description: Treatment with peginterferon plus daily low dose (800 mg) or weight-based ribavirin (800-1400 mg) for 24 to 48 weeks has achieved 70-93% sustained virologic response (SVR) rates in patients with genotype 2 or 3 chronic hepatitis C (CHC). Recently, a large randomized study has shown that patients with genotype 2 or 3 CHC have comparable SVR rates for those who received peginterferon for 24 or 48 weeks, and who received daily low dose (800 mg) or standard dose (1000-1200 mg) ribavirin. Therefore, the currently recommended treatment for these patients is 24 weeks of peginterferon plus low dose ribavirin. Because of the high response rates, several studies have shown that when these patients had rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV) RNA levels, at week 4 of peginterferon plus weight-based ribavirin, 12-16 weeks of treatment could have 82-94% SVR rates. However, treatment with peginterferon plus low dose ribavirin for 24 weeks showed significantly higher SVR rates than that for 16 weeks (85% vs. 79%) in these patients who achieved RVR. While studies showed concordant results in SVR rates for patients with genotype 3 CHC who received peginterferon plus low dose or weight-based ribavirin for 16 or 24 weeks, the SVR rates stratified by RVR showed great differences in patients with genotype 2 CHC who received such treatment. Currently, there are no studies on the direct comparison of low dose versus weight-based ribavirin, and of 16 to 24 weeks of treatment stratified by RVR for patients with genotype 2 CHC. We aimed to conduct a randomized trial to determine the optimal ribavirin dose and treatment duration of peginterferon plus ribavirin for patients with genotype 2 CHC based on RVR studies.

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

Criteria:

Inclusion Criteria:

- Treatment naïve

- Age 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 Taqman HCV Monitor v2. 0, Roche

Diagnostics) with dynamic range 25 ~ 391000000 IU/ml

- HCV genotype 2 (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 grams per deciliter for men and < 12 grams per deciliter for

women)

- Neutropenia (neutrophil count < 1,500 per cubic milliliter)

- Thrombocytopenia (platelets < 90,000 per cubic milliliter)

- Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

- Chronic alcohol abuse (daily consumption > 20 grams 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 use contraception

- Unwilling to sign informed consent

Chen-Hua Liu, MD, Phone: +886-2-23123456, Ext: 3572, Email: jacque_liu@mail2000.com.tw

National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan; Recruiting
Shih-Jer Hsu, MD, Principal Investigator

Kaohsiung Medical University, Kaohsiung, Taiwan; Recruiting
Ming-Lung Yu, MD, PhD
Ming-Lung Yu, MD, PhD, Principal Investigator
Wan-Long Chuang, MD, PhD, Principal Investigator

Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan; Recruiting
Chia-Yen Dai, MD, Ms
Chia-Yen Dai, MD, Ms, Principal Investigator
Jee-Fu Huang, MD, Principal Investigator

Paochien Hospital, Pingtung, Taiwan; Recruiting
Chang-Fu Chiu, MD
Chang-Fu Chiu, MD, Principal Investigator

Taichung Veterans General Hospital, Taichung, Taiwan; Recruiting
Sheng-Shun Yang, MD, Principal Investigator

Far Eastern Memorial Hospital, Taipei, Taiwan; Recruiting
Cheng-Chao Liang, MD, Principal Investigator

Ren-Ai Branch, Taipei Municipal Hospital, Taipei, Taiwan; Recruiting
Chih-Lin Lin, MD, Principal Investigator

National Taiwan University Hospital, Taipei 100, Taiwan; Recruiting
Chen-Hua Liu, MD, Principal Investigator
Jia-Horng Kao, MD, PhD, Principal Investigator
Ding-Shinn Chen, MD, Principal Investigator
Ming-Yang Lai, MD, PhD, Principal Investigator
Pei-Jer Chen, MD, PhD, Principal Investigator
Chun-Jen Liu, MD,PhD, Principal Investigator

Buddhist Xindian Tzu Chi General Hospital, Taipei, Taiwan; Recruiting
Ching-Sheng Hsu, MD, Principal Investigator
Chia-Chi Wang, MD, Principal Investigator
Tai-Chung Tseng, MD, Principal Investigator

Related publications:

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, 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.

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.

Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, Sarrazin C, Harvey J, Brass C, Albrecht J. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004 Jun;40(6):993-9. Erratum in: J Hepatol. 2005 Mar;42(3):434.

Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, Shafran SD, Barange K, Lin A, Soman A, Zeuzem S; ACCELERATE Investigators. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007 Jul 12;357(2):124-34.

Strader DB, Wright T, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004 Apr;39(4):1147-71. No abstract available. Erratum in: Hepatology. 2004 Jul;40(1):269.

Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology. 2004 Dec;40(6):1260-5.

von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Haussinger D, Herrmann E, Zeuzem S. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005 Aug;129(2):522-7.

Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005 Jun 23;352(25):2609-17.

Yu ML, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, Chiu CF, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007 Apr;56(4):553-9. Epub 2006 Sep 6.

Starting date: June 2006
Last updated: November 30, 2010