A Retrospective Study to Assess the Impact of the Use of Interferon in Patients With Chronic Hepatitis C (DECISION)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01280656
• Collaborator: (none)
• Enrollment: 660
• Locations: 37
• Duration (Months): 41
• Patients Per Site: 17.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This retrospective study will assess the sustained virologic response and the safety of two different interferons (pegylated or conventional) in patients with chronic hepatitis C. Data will be collected for 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Conventional Interferon; Drug: Peginterferon Alfa-2a; Drug: Peginterferon Alfa-2b; Drug: Ribavirin

Study Design

• Study Type: Observational
• Actual Enrollment: 660 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Retrospective Study to Evaluate the Impact of Using Interferon (Pegylated or Not) in the Treatment of Patients With Chronic Hepatitis C in Brazil (DECISION)
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Conventional Interferon Plus Ribavirin Eligible participants who will receive conventional interferon plus ribavirin for Chronic Hepatitis C (CHC) according to the standard of care and aligned with the local prescription instructions will be observed during treatment period (48 weeks) and follow up period (24 weeks).	Drug: Conventional Interferon; Conventional interferon according to the standard of care and aligned with the local prescription instructions; Drug: Ribavirin; Ribavirin according to the standard of care and aligned with the local prescription instructions
Peginterferon Alfa-2a Plus Ribavirin Eligible participants who will receive peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions will be observed during treatment period (48 weeks) and follow up period (24 weeks).	Drug: Peginterferon Alfa-2a; Peginterferon alfa-2a according to the standard of care and aligned with the local prescription instructions; Drug: Ribavirin; Ribavirin according to the standard of care and aligned with the local prescription instructions
Peginterferon Alfa-2b Plus Ribavirin Eligible participants who will receive peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions will be observed during treatment period (48 weeks) and follow up period (24 weeks).	Drug: Peginterferon Alfa-2b; Peginterferon alfa-2b according to the standard of care and aligned with the local prescription instructions; Drug: Ribavirin; Ribavirin according to the standard of care and aligned with the local prescription instructions

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response at 12 Weeks After End of Treatment [At Week 60]

   Sustained virological response (SVR) was defined as virological response at 12 weeks after end of treatment (EOT). Virologic response was either defined as having undetectable (that is, no hepatitis C virus Ribonucleic acid [HCV RNA] was detected in the participants' plasma samples) or less than 50 international units/milliliter (IU/mL) HCV RNA (that is, the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples). EOT= Week 48. Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response at 24 Weeks After End of Treatment [At Week 72]

   SVR was defined as virological response at 24 weeks after EOT, EOT= Week 48. Virologic response was either defined as having undetectable (that is, no hepatitis C virus Ribonucleic acid [HCV RNA] was detected in the participants' plasma samples) or less than 50 IU/mL HCV RNA (that is, the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples). Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy.

2. Number of Participants With Interferon Dose Reduction Rates in Function of the Interferon Type Being Used [At Week 24]

   The number of participants with Interferon dose reduction rates in function of the interferon type being used are reported

3. Percentage of Participants With Early Virologic Response at Week 12 [At Week 12]

   An early virologic response (EVR) was defined as a HCV-RNA decrease of at least two logarithmic scales (2 Log) or 100 times the pretreatment value or non-detection at Week 12 of treatment period.

4. Percentage of Participants With Sustained Virologic Response Treated at Interferon Application Centers and Treated at Home [At Week 60 (SVR 12) and Week 72 (SVR 24)]

   The percentage of participants with SVR-12 and SVR-24 treated at interferon application centers (IAC) and treated at home are presented.

5. Percentage of Participants Who Were Treated at Interferon Application Centers and at Home and Discontinued Treatment [Up to Week 48]

   The percentage of participants who were treated at interferon application centers and at home and who discontinued treatment is presented. Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy.

6. Mean Percentage Reduction of Hemoglobin in Treatment Responders and Treatment Non-Responders [Up to Week 72]

   The average percentage reduction of hemoglobin (Hb) in treatment responders and treatment non-responders between the conventional group, peginterferon alfa-2a plus and peginterferon alfa-2b is presented. Participants with undetectable HCV RNA at specified time points (Weeks 4/12/18/24/48) were considered as treatment responders. Participants with positive viral load (detectable HCV RNA) at end of treatment regardless of the treatment duration were considered as treatment non-responders.

7. Percentage of Participants With Rapid Virologic Response at Week 4 [At Week 4]

   Rapid virologic response was defined as qualitative or quantitative HCV-RNA (viral load) undetectable (below the lower limit of detection) at Week 4 of treatment period.

8. Percentage of Participants With Virologic Response at End of Treatment [At Week 48]

   Virologic response at EOT was defined as undetectable HCV-RNA at EOT (regardless in which week treatment was concluded). EOT = Week 48.

9. Percentage of Participants With Virologic Relapse up to Week 72 [Up to Week 72]

   Virologic relapse was defined as undetectable HCV-RNA at end of treatment and detectable HCV-RNA at the last follow-up assessment available. If the participant was a responder at end of treatment and was not submitted to any viral load assessment during the follow-up period, he was considered a relapser.

10. Percentage of Participants With Null Response or No Responder at End of Treatment [At Week 48]

    Null response or no responders were defined as those participants presenting positive viral load at EOT (regardless of the treatment duration). EOT= Week 48.

11. Percentage of Participants Who Discontinued Treatment Due to Adverse Events [Up to Week 48]

    The percentage of participants with treatment discontinuation rates due to adverse events (AE) between conventional group, peginterferon alfa-2a and peginterferon alfa-2b is presented.

12. Number of Participants With Any Adverse Events and Any Serious Adverse Events [Up to Week 72]

    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients, >/=18 years and <70 years of age

• Diagnosis of hepatitis C

• Assessment of viral load prior to treatment (mandatory for genotype 1 only)

• Liver biopsy

• Co-morbidities data

• Use of interferon (pegylated or conventional) and ribavirin to treat hepatitis C infection genotype 2 and 3 and pegylated interferon plus ribavirin to treat hepatitis C infection genotype 1

• Above mentioned treatment started between 01-Sep-2007 and 31-Aug-2008

Exclusion Criteria:

• Co-infection with human immunodeficiency virus

• Co-infection with hepatitis B virus

• Presence of hepatocarcinoma

• Patients submitted to hemodialysis

• Organ transplant patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Rio Branco	AC	Brazil	69908-210
2		Manaus	AM	Brazil	69040-000
3		Salvador	BA	Brazil	41110-170
4		Vitoria	ES	Brazil	29043-260
5		Goiania	GO	Brazil	74535170
6		Sao Luis	MA	Brazil	65020560
7		Pouso Alegre	MG	Brazil	37550-000
8		Uberaba	MG	Brazil	38025-180
9		Campo Grande - MS	MS	Brazil	79034-000
10		Belem	PA	Brazil	66050-380
11		Recife	PE	Brazil	50100-130
12		Recife	PE	Brazil	50670-420
13		Curitiba	PR	Brazil	80060-900
14		Curitiba	PR	Brazil	80810-040
15		Niteroi	RJ	Brazil	24033-900
16		Nova Iguacu	RJ	Brazil	26030-380
17		Rio de Janeiro	RJ	Brazil	20270-004
18		Porto Velho	RO	Brazil	78812-329
19		Porto Alegre	RS	Brazil	90035-003
20		Porto Alegre	RS	Brazil	90610-000
21		Rio Grande	RS	Brazil	96200-310
22		Sao Jose Do Rio Preto	SC	Brazil	15090-000
23		Aracaju	SE	Brazil	49060-100
24		Botucatu	SP	Brazil	18600-400
25		Campinas	SP	Brazil	13060-803
26		Ribeirao Preto	SP	Brazil	14049-900
27		Ribeirao Preto	SP	Brazil	14085-410
28		Santo Andre	SP	Brazil	09060-650
29		Santos	SP	Brazil	11015470
30		Sao Paulo	SP	Brazil	01246-000
31		Sao Paulo	SP	Brazil	01323-020
32		Sao Paulo	SP	Brazil	04039-004
33		Sao Paulo	SP	Brazil	04040-002
34		Sao Paulo	SP	Brazil	04040-003
35		Sao Paulo	SP	Brazil	05403-000
36		Sao Paulo	SP	Brazil	05403-010
37		Sorocaba	SP	Brazil	18047-600

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01280656
• Other Study ID Numbers: ML22995
• First Posted: Jan 21, 2011
• Last Update Posted: Nov 29, 2016
• Last Verified: Oct 1, 2016

• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Interferons; Ribavirin; Peginterferon alfa-2a; Peginterferon alfa-2b

Study Results

Participant Flow

Recruitment Details	A total of 660 participants were enrolled from 39 centers in Brazil. The study was conducted from January 2010 to June 2013.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for Chronic Hepatitis C (CHC) according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Period Title: Overall Study
STARTED	62	312	286
COMPLETED	59	265	223
NOT COMPLETED	3	47	63

Baseline Characteristics

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin	Total
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Total of all reporting groups
Overall Participants	62	312	286	660
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.4 (8.6)	49.2 (10.7)	49.5 (9.5)	49.5 (10.0)
Sex: Female, Male (Count of Participants)
Female	22 35.5%	188 60.3%	147 51.4%	357 54.1%
Male	40 64.5%	124 39.7%	139 48.6%	303 45.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response at 12 Weeks After End of Treatment
Description	Sustained virological response (SVR) was defined as virological response at 12 weeks after end of treatment (EOT). Virologic response was either defined as having undetectable (that is, no hepatitis C virus Ribonucleic acid [HCV RNA] was detected in the participants' plasma samples) or less than 50 international units/milliliter (IU/mL) HCV RNA (that is, the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples). EOT= Week 48. Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy.
Time Frame	At Week 60

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of participants who fulfilled all inclusion/ exclusion criteria. The analysis was performed in participants with virologic response at EOT in each group (16, 126, and 101 respectively).

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	16	126	101
Number [percentage of participants]	0 0%	7.1 2.3%	20.8 7.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response at 24 Weeks After End of Treatment
Description	SVR was defined as virological response at 24 weeks after EOT, EOT= Week 48. Virologic response was either defined as having undetectable (that is, no hepatitis C virus Ribonucleic acid [HCV RNA] was detected in the participants' plasma samples) or less than 50 IU/mL HCV RNA (that is, the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples). Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy.
Time Frame	At Week 72

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria. The analysis was performed in participants with virologic response at EOT in each group (16, 126, and 101 respectively).

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	16	126	101
Number [percentage of participants]	62.5 100.8%	74.6 23.9%	72.3 25.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.693
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Number of Participants With Interferon Dose Reduction Rates in Function of the Interferon Type Being Used
Description	The number of participants with Interferon dose reduction rates in function of the interferon type being used are reported
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria. The analysis was performed in the participants who were available for interferon dose reduction rates in each group (56, 302, and 280 respectively).

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	56	302	280
Number [participants]	1 1.6%	9 2.9%	29 10.1%

4. Secondary Outcome

Title	Percentage of Participants With Early Virologic Response at Week 12
Description	An early virologic response (EVR) was defined as a HCV-RNA decrease of at least two logarithmic scales (2 Log) or 100 times the pretreatment value or non-detection at Week 12 of treatment period.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	62	312	286
Number [percentage of participants]	14.5 23.4%	37.2 11.9%	35.0 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.573
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response Treated at Interferon Application Centers and Treated at Home
Description	The percentage of participants with SVR-12 and SVR-24 treated at interferon application centers (IAC) and treated at home are presented.
Time Frame	At Week 60 (SVR 12) and Week 72 (SVR 24)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria. The analysis was performed in participants with virologic response at EOT in each group excluding participants treated at an unknown location (2/16, 5/126, and 9/101 respectively).

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	14	121	92
SVR-12, treated at IAC (n=0, 40, 35)	NA NaN	5.0 1.6%	2.9 1%
SVR-12, treated at home (n=14, 81, 57)	0 0%	8.6 2.8%	33.3 11.6%
SVR-24, treated at IAC (n=0, 40, 35)	NA NaN	80.0 25.6%	77.1 27%
SVR-24, treated at home (n=14, 81, 57)	64.3 103.7%	75.3 24.1%	68.4 23.9%

6. Secondary Outcome

Title	Percentage of Participants Who Were Treated at Interferon Application Centers and at Home and Discontinued Treatment
Description	The percentage of participants who were treated at interferon application centers and at home and who discontinued treatment is presented. Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria. The analysis excluded participants treated at an unknown location (7/62, 10/312, and 23/286 respectively)

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	55	302	263
At the site (n=0,98,126)	NA NaN	17.4 5.6%	17.5 6.1%
At home (n=55,204,137)	5.5 8.9%	11.8 3.8%	21.9 7.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments	Mean at the site
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.982
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments	Mean at home
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Mean Percentage Reduction of Hemoglobin in Treatment Responders and Treatment Non-Responders
Description	The average percentage reduction of hemoglobin (Hb) in treatment responders and treatment non-responders between the conventional group, peginterferon alfa-2a plus and peginterferon alfa-2b is presented. Participants with undetectable HCV RNA at specified time points (Weeks 4/12/18/24/48) were considered as treatment responders. Participants with positive viral load (detectable HCV RNA) at end of treatment regardless of the treatment duration were considered as treatment non-responders.
Time Frame	Up to Week 72

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria. Treatment responders and non-responders for whom data was available were considered for this outcome measure.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	10	73	63
Responders (n=0,19,15)	NA (NA)	14.4 (8.5)	15.8 (10.3)
Non-responders (n=10,54,48)	18.3 (9.5)	9.8 (27.7)	12.6 (11.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin
	Comments	Responders vs Non-responders
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.476
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2b Plus Ribavirin
	Comments	Responders vs Non-Responders
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.320
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Percentage of Participants With Rapid Virologic Response at Week 4
Description	Rapid virologic response was defined as qualitative or quantitative HCV-RNA (viral load) undetectable (below the lower limit of detection) at Week 4 of treatment period.
Time Frame	At Week 4

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	62	312	286
Number [percentage of participants]	6.5 10.5%	21.2 6.8%	20.3 7.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.792
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Percentage of Participants With Virologic Response at End of Treatment
Description	Virologic response at EOT was defined as undetectable HCV-RNA at EOT (regardless in which week treatment was concluded). EOT = Week 48.
Time Frame	At Week 48

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	62	312	286
Number [percentage of participants]	25.8 41.6%	40.4 12.9%	35.3 12.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.202
	Comments
	Method	Chi-squared
	Comments

10. Secondary Outcome

Title	Percentage of Participants With Virologic Relapse up to Week 72
Description	Virologic relapse was defined as undetectable HCV-RNA at end of treatment and detectable HCV-RNA at the last follow-up assessment available. If the participant was a responder at end of treatment and was not submitted to any viral load assessment during the follow-up period, he was considered a relapser.
Time Frame	Up to Week 72

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria. The analysis was performed in participants with virologic response at EOT in each group (16, 126, and 101 respectively).

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	16	126	101
Number [percentage of participants]	37.5 60.5%	22.2 7.1%	22.8 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.921
	Comments
	Method	Chi-squared
	Comments

11. Secondary Outcome

Title	Percentage of Participants With Null Response or No Responder at End of Treatment
Description	Null response or no responders were defined as those participants presenting positive viral load at EOT (regardless of the treatment duration). EOT= Week 48.
Time Frame	At Week 48

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	62	312	286
Number [percentage of participants]	74.2 119.7%	59.6 19.1%	64.7 22.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.202
	Comments
	Method	Chi-squared
	Comments

12. Secondary Outcome

Title	Percentage of Participants Who Discontinued Treatment Due to Adverse Events
Description	The percentage of participants with treatment discontinuation rates due to adverse events (AE) between conventional group, peginterferon alfa-2a and peginterferon alfa-2b is presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	62	312	286
Number [percentage of participants]	1.6 2.6%	4.5 1.4%	4.6 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginterferon Alfa-2a Plus Ribavirin, Peginterferon Alfa-2b Plus Ribavirin
	Comments	Total
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.973
	Comments
	Method	Chi-squared
	Comments

13. Secondary Outcome

Title	Number of Participants With Any Adverse Events and Any Serious Adverse Events
Description	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes.
Time Frame	Up to Week 72

Outcome Measure Data

Analysis Population Description

The ITT population consisted of participants who fulfilled all inclusion/ exclusion criteria.

Arm/Group Title	Conventional Interferon Plus Ribavirin	Peginterferon Alfa-2a Plus Ribavirin	Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).	Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were observed during treatment period (48 weeks) and follow up period (24 weeks).
Measure Participants	62	312	286
any AE	57 91.9%	285 91.3%	264 92.3%
any SAE	2 3.2%	15 4.8%	9 3.1%

Adverse Events

Time Frame	Up to Week 72
Adverse Event Reporting Description	Serious adverse events and non-serious adverse events are reported in ITT population set.
Arm/Group Title	Conventional Interferon Plus Ribavirin		Peginterferon Alfa-2a Plus Ribavirin		Peginterferon Alfa-2b Plus Ribavirin
Arm/Group Description	Eligible participants who received conventional interferon plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were retrospectively assessed up to a minimum of 12 weeks after the end of therapy.		Eligible participants who received peginterferon alfa-2a plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were retrospectively assessed up to a minimum of 12 weeks after the end of therapy		Eligible participants who received peginterferon alfa-2b plus ribavirin for CHC according to the standard of care and aligned with the local prescription instructions were retrospectively assessed up to a minimum of 12 weeks after the end of therapy.
All Cause Mortality
	Conventional Interferon Plus Ribavirin		Peginterferon Alfa-2a Plus Ribavirin		Peginterferon Alfa-2b Plus Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Conventional Interferon Plus Ribavirin		Peginterferon Alfa-2a Plus Ribavirin		Peginterferon Alfa-2b Plus Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/62 (3.2%)		15/312 (4.8%)		9/286 (3.1%)
Blood and lymphatic system disorders
Anaemia	0/62 (0%)		1/312 (0.3%)		3/286 (1%)
Bone marrow failure	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Neutropaenia	0/62 (0%)		0/312 (0%)		1/286 (0.3%)
Febrile neutropaenia	0/62 (0%)		0/312 (0%)		1/286 (0.3%)
Thrombocytopaenia	0/62 (0%)		0/312 (0%)		1/286 (0.3%)
Cardiac disorders
Thoracic pain	0/62 (0%)		0/312 (0%)		1/286 (0.3%)
Atrial fibrillation	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Gastrointestinal disorders
Appendicitis	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Abdominal pain	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Inguinal hernia	1/62 (1.6%)		0/312 (0%)		0/286 (0%)
Hepatobiliary disorders
Gallstones	0/62 (0%)		0/312 (0%)		1/286 (0.3%)
Immune system disorders
Cryoglobulinaemia	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Infections and infestations
Urinary tract infection	0/62 (0%)		1/312 (0.3%)		1/286 (0.3%)
Cell tissue inflammation	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Osteomyelitis	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Injury, poisoning and procedural complications
Multiple injuries	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Metabolism and nutrition disorders
Diabetic Ketoacidosis	0/62 (0%)		0/312 (0%)		1/286 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Vocal cord neoplasia	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Breast tumour	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Psychiatric disorders
Depression	1/62 (1.6%)		0/312 (0%)		0/286 (0%)
Reproductive system and breast disorders
Breast mass	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Pneumonia	0/62 (0%)		0/312 (0%)		1/286 (0.3%)
Vascular disorders
Thrombophlebitis	0/62 (0%)		1/312 (0.3%)		0/286 (0%)
Other (Not Including Serious) Adverse Events
	Conventional Interferon Plus Ribavirin		Peginterferon Alfa-2a Plus Ribavirin		Peginterferon Alfa-2b Plus Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/62 (88.7%)		275/312 (88.1%)		262/286 (91.6%)
Blood and lymphatic system disorders
Anaemia	11/62 (17.7%)		109/312 (34.9%)		111/286 (38.8%)
Leucopaenia	1/62 (1.6%)		14/312 (4.5%)		20/286 (7%)
Neutropaenia	3/62 (4.8%)		60/312 (19.2%)		45/286 (15.7%)
Thrombocytopaenia	3/62 (4.8%)		27/312 (8.7%)		21/286 (7.3%)
Gastrointestinal disorders
Diarrhoea	3/62 (4.8%)		21/312 (6.7%)		27/286 (9.4%)
Abdominal pain	1/62 (1.6%)		10/312 (3.2%)		16/286 (5.6%)
High abdominal pain	7/62 (11.3%)		25/312 (8%)		23/286 (8%)
Nausea	10/62 (16.1%)		57/312 (18.3%)		45/286 (15.7%)
Vomiting	7/62 (11.3%)		21/312 (6.7%)		20/286 (7%)
General disorders
Asthenia	23/62 (37.1%)		114/312 (36.5%)		107/286 (37.4%)
Pain	3/62 (4.8%)		19/312 (6.1%)		30/286 (10.5%)
Flu condition	3/62 (4.8%)		25/312 (8%)		50/286 (17.5%)
Fatigue	9/62 (14.5%)		36/312 (11.5%)		35/286 (12.2%)
Malaise	7/62 (11.3%)		19/312 (6.1%)		21/286 (7.3%)
Pyrexia	16/62 (25.8%)		65/312 (20.8%)		66/286 (23.1%)
Metabolism and nutrition disorders
Decreased appetite	12/62 (19.4%)		75/312 (24%)		52/286 (18.2%)
Cachexia	2/62 (3.2%)		9/312 (2.9%)		17/286 (5.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/62 (9.7%)		16/312 (5.1%)		16/286 (5.6%)
Pain in extremities	1/62 (1.6%)		15/312 (4.8%)		16/286 (5.6%)
Dorsalgia	1/62 (1.6%)		9/312 (2.9%)		19/286 (6.6%)
Myalgia	8/62 (12.9%)		51/312 (16.3%)		33/286 (11.5%)
Nervous system disorders
Headache	19/62 (30.6%)		67/312 (21.5%)		67/286 (23.4%)
Insomnia	6/62 (9.7%)		43/312 (13.8%)		30/286 (10.5%)
Dizziness	5/62 (8.1%)		28/312 (9%)		25/286 (8.7%)
Psychiatric disorders
Anxiety	2/62 (3.2%)		12/312 (3.8%)		19/286 (6.6%)
Depression	2/62 (3.2%)		36/312 (11.5%)		35/286 (12.2%)
Irritability	4/62 (6.5%)		41/312 (13.1%)		31/286 (10.8%)
Respiratory, thoracic and mediastinal disorders
Cough	0/62 (0%)		23/312 (7.4%)		11/286 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia	8/62 (12.9%)		28/312 (9%)		26/286 (9.1%)
Itch	9/62 (14.5%)		50/312 (16%)		44/286 (15.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.