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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Hepatitis C, Chronic
Intervention:	Drug: Pegylated interferon alfa-2a plus ribavirin

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment period: 2006 June to September Location: academic centers

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No wash out period in the study; all were treatment-naive All the patients who were eligible in the study were assigned to either groups without exclusion.

Reporting Groups

	Description
Peginterferon 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
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

Participant Flow: Overall Study

	Peginterferon and Ribavirin (24 Weeks)	Peginterferon and Ribavirin (48 Weeks)
STARTED	154	154
COMPLETED	147	148
NOT COMPLETED	7	6
Adverse Event	6	2
Lack of Efficacy	0	2
Lost to Follow-up	0	2
Withdrawal by Subject	1	0

Baseline Characteristics

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Reporting Groups

	Description
Peginterferon 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
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
Total	Total of all reporting groups

Baseline Measures

	Peginterferon and Ribavirin (24 Weeks)	Peginterferon and Ribavirin (48 Weeks)	Total
Number of Participants [units: participants]	154	154	308
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	122	128	250
>=65 years	32	26	58
Age [units: years] Mean ± Standard Deviation	54 ± 10	53 ± 11	53 ± 10
Gender [units: participants]
Female	66	67	133
Male	88	87	175
Region of Enrollment [units: participants]
Taiwan	154	154	308

Outcome Measures

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1. Primary:

Sustained Virologic Response [ Time Frame: 18 months ]

Measure Type	Primary
Measure Title	Sustained Virologic Response
Measure Description	Undetectable HCV RNA 6 months off therapy
Time Frame	18 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention-to-treat (ITT) analysis by last observation carried forward

Reporting Groups

	Description
Peginterferon 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
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

Measured Values

	Peginterferon and Ribavirin (24 Weeks)	Peginterferon and Ribavirin (48 Weeks)
Number of Participants Analyzed [units: participants]	154	154
Sustained Virologic Response [units: participants]	87	117

Statistical Analysis 1 for Sustained Virologic Response

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	< 0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis: no difference between 2 groups SVR estimation: 24 weeks (60%), 48 weeks (75%) alfa erros: 0.05, power: 0.80
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

2. Primary:

Sustained Biochemical Response [ Time Frame: 18 months ]

Measure Type	Primary
Measure Title	Sustained Biochemical Response
Measure Description	Sustained biochemical response (SBR): alanine aminotransferase (ALT) normalization
Time Frame	18 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with end of follow-up alanine aminotransferase (ALT) levels

Reporting Groups

	Description
Peginterferon 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
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

Measured Values

	Peginterferon and Ribavirin (24 Weeks)	Peginterferon and Ribavirin (48 Weeks)
Number of Participants Analyzed [units: participants]	147	148
Sustained Biochemical Response [units: Participants]	75	107

No statistical analysis provided for Sustained Biochemical Response

3. Secondary:

Treatment-related Withdrawal Rate [ Time Frame: 18 months ]

Measure Type	Secondary
Measure Title	Treatment-related Withdrawal Rate
Measure Description	Treatment-related withdrawal rate: patients who prematurely discontinued treatment due to treatment-related adverse events
Time Frame	18 months
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Peginterferon 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
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

Measured Values

	Peginterferon and Ribavirin (24 Weeks)	Peginterferon and Ribavirin (48 Weeks)
Number of Participants Analyzed [units: participants]	154	154
Treatment-related Withdrawal Rate [units: Participants]	6	14

No statistical analysis provided for Treatment-related Withdrawal Rate

4. Secondary:

Histologic Response [ Time Frame: 18 months ]

Measure Type	Secondary
Measure Title	Histologic Response
Measure Description	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
Time Frame	18 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data included for analysis only for patients with paired liver biopsies.

Reporting Groups

	Description
Peginterferon 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
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

Measured Values

	Peginterferon and Ribavirin (24 Weeks)	Peginterferon and Ribavirin (48 Weeks)
Number of Participants Analyzed [units: participants]	120	124
Histologic Response [units: Participants]	71	97

No statistical analysis provided for Histologic Response

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Chen-Hua Liu, MD
Organization: National Taiwan University Hospital
phone: 886223123456 ext 63572
e-mail: jacque_liu@mail2000.com.tw

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, 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.

[No authors listed] 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. No abstract available.

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.

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. 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.

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:

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.

Responsible Party:	Dr. Jia-Horng Kao, National Taiwan University Hospital
ClinicalTrials.gov Identifier:	NCT00495131 History of Changes
Other Study ID Numbers:	200705080M
Study First Received:	June 29, 2007
Results First Received:	December 21, 2008
Last Updated:	September 7, 2009
Health Authority:	Taiwan: Department of Health