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Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV)

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ClinicalTrials.gov Identifier: NCT00078403
Recruitment Status : Completed
First Posted : February 25, 2004
Results First Posted : April 27, 2011
Last Update Posted : January 27, 2017
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HIV Infections
Hepatitis C
Liver Disease
Interventions Drug: Peginterferon alfa-2a
Drug: Ribavirin
Enrollment 333
Recruitment Details People with hepatitis C virus (HCV)/HIV coinfection were recruited for participation in this study.
Pre-assignment Details 330 participants were to receive 12 weeks of PEG+RBV to determine EVR status. Of the 330, 33 discontinued prior to week 12; 113 were non-EVRs, 80 of whom were randomized between Arms A and B; and 184 achieved EVR, 170 of whom were eligible to continue. 169 of the 170 were assigned to Arm C and one was inadvertently randomized between Arms A and B.
Arm/Group Title Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) OL (PEG-IFN, RBV) Then OL Randomized (Observation) OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks. At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment). At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Period Title: Overall Study
Started 44 [1] 42 [2] 169
Completed 26 26 141
Not Completed 18 16 28
[1]
Eligible at pre-assignment (40), direct (2), Arm C week 36 non-response (1), EVR inadvertently (1).
[2]
Eligible at pre-assignment (40), direct (1), Arm C week 36 non-response (1).
Arm/Group Title Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) OL (PEG-IFN, RBV) Then OL Randomized (Observation) OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) Total
Hide Arm/Group Description At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks. At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment). At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation. Total of all reporting groups
Overall Number of Baseline Participants 44 42 169 255
Hide Baseline Analysis Population Description
All Arm A, B and C participants.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 42 participants 169 participants 255 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
44
 100.0%
42
 100.0%
169
 100.0%
255
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 42 participants 169 participants 255 participants
48.8  (6.7) 48.1  (5.8) 47.2  (7.1) 47.6  (6.8)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 42 participants 169 participants 255 participants
Female
12
  27.3%
12
  28.6%
19
  11.2%
43
  16.9%
Male
32
  72.7%
30
  71.4%
150
  88.8%
212
  83.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 44 participants 42 participants 169 participants 255 participants
United States 41 40 168 249
Puerto Rico 3 2 1 6
1.Primary Outcome
Title Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS)
Hide Description SCMFS is the difference between the Metavir fibrosis scores of the study exit and study entry liver biopsies where the difference is scaled to one year. The SCMFS assesses the annualized change in the severity of liver fibrosis on a continuous scale from -4.0 Metavir units per year (reduced fibrosis over time, a positive study outcome) to +4.0 Metavir units per year (increased fibrosis over time).
Time Frame Baseline and at week 72 or premature discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
62 Arm A and B participants who had follow-up liver biopsy performed or those who had Week 72 potential as of May 2, 2007 but no follow-up liver biopsy. In the unadjusted ITT analysis, the participants without SCMFS available were assigned the highest SCMFS (+2).
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 33 29 0
Median (Inter-Quartile Range)
Unit of Measure: Metavir units per one year (52 weeks)
0
(0 to 1.37)
0
(0 to 2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN), B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)
Comments Accrual and follow-up on Arms A and B were halted for futility at the first independent interim review of the primary endpoint conducted on May 2, 2007.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments P-value is pre-specified 1-sided test that PEG slows liver fibrosis progression. Accrual and follow-up on Arms A and B were halted at interim review for lack of fibrosis progression in Arm B (control arm). P-value is unadjusted for interim analysis.
Method Exact Wilcoxon rank sum test
Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)
Hide Description Qualitative plasma HCV viral load was categorized as less than 60 IU/mL vs greater than or equal to 60 IU/mL where 60 IU/mL is the lower limit of qualitative assay used in Steps 2 and 3.
Time Frame Arms A and B: Weeks 0, 12, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 60, 72, 84
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Week 0--Number of participants with HCV RNA data 44 42 164
Week 0--Number of participants with detectable HCV 42 42 53
Week 12--Number of participants with HCV RNA data 42 34 158
Week 12-Number of participants with detectable HCV 40 34 31
Week 24--Number of participants with HCV RNA data 36 35 163
Week 24-Number of participants with detectable HCV 35 35 39
Week 36--Number of participants with HCV RNA data 0 0 158
Week 36-Number of participants with detectable HCV NA [1]  NA [1]  41
Week 48--Number of participants with HCV RNA data 31 28 0
Week 48-Number of participants with detectable HCV 31 28 NA [1] 
Week 60--Number of participants with HCV RNA data 0 0 137
Week 60-Number of participants with detectable HCV NA [1]  NA [1]  34
Week 72--Number of participants with HCV RNA data 27 22 135
Week 72-Number of participants with detectable HCV 27 22 51
Week 84--Number of participants with HCV RNA data 0 0 137
Week 84-Number of participants with detectable HCV NA [1]  NA [1]  50
[1]
Test not specified in protocol at this time point.
3.Secondary Outcome
Title Time-scaled Change in Ishak Liver Inflammation Score (SCIIS)
Hide Description Liver biopsies were performed within 42 days prior to randomization between Arms A and B while the participant remained on PEG-IFN plus RBV (=entry biopsy) and again at week 72 or premature study discontinuation (=exit biopsy). SCIIS was defined as the difference between the Ishak inflammation score of the exit biopsy and the Ishak inflammation score of the entry biopsy, where the difference is scaled to one year.
Time Frame Baseline and at week 72 or premature discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with SCIIS available (Complete Cases)
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 0
Median (Inter-Quartile Range)
Unit of Measure: Ishak units per one year (52 weeks)
0
(-0.75 to 1.79)
1.31
(0 to 2.10)
4.Secondary Outcome
Title Number of Participants With Anemia
Hide Description Number of participants with anemia by grade (defined by hemoglobin level in grams per deciliter; g/dL). DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = hemoglobin of 8 to 9.4 g/dl; Grade 2 = 7 to 7.9 g/dl; Grade 3 = 6.5 to 6.9 g/dl; Grade 4 = below 6.5 g/dl.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Anemia >= Grade 2 1 0 6
Grade 2 0 0 3
Grade 3 0 0 1
Grade 4 1 0 2
5.Secondary Outcome
Title Number of Participants With Neutropenia
Hide Description Number of participants with neutropenia by grade (defined by absolute neutrophil count [ANC] per cubic millimeter; mm^3). DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = ANC of 1000 to 1500 /mm^3; Grade 2 = 750 to 999 /mm^3; Grade 3 = 500 to 749 /mm^3; Grade 4 = below 500 /mm^3.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Neutropenia >= Grade 2 20 10 96
Grade 2 7 4 38
Grade 3 10 5 37
Grade 4 3 1 21
6.Secondary Outcome
Title Number of Participants With Thrombocytopenia
Hide Description Number of participants with thrombocytopenia by grade (defined by platelet count per cubic millimeter; mm^3). DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = platelets of 75,000 to 99,000 /mm^3; Grade 2 = 50,000 to 74,999 /mm^3; Grade 3 = 20,000 to 49,999 /mm^3; Grade 4 = below 20,000 /mm^3.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Thrombocytopenia >= Grade 2 14 4 31
Grade 2 10 3 25
Grade 3 4 1 5
Grade 4 0 0 1
7.Secondary Outcome
Title Number of Participants With Depression and/or Other Psychological Events
Hide Description Depression and other psychological events. DAIDS Toxicity Grading Table (1992) was used for grading. The protocol required reporting of depression and other psychological events of Grade 3 or higher or if led to a change in treatment, regardless of grade.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Any psychological 3 1 19
Grade 3 2 1 18
Grade 4 1 0 1
8.Secondary Outcome
Title Number of Participants With High-grade Signs and Symptoms or Laboratory Values
Hide Description Number of participants with high-grade (Grade 3 or higher) signs and symptoms or laboratory values. DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = transient/mild discomfort, no limitation in activity, no medical intervention; Grade 2 = mild/moderate limitation in activity, some assistance, no/minimal medical intervention; Grade 3 = marked limitation in activity, some assistance, medical intervention required); Grade 4 = extreme limitation in activity, significant medical intervention, assistance, hospitalization.
Time Frame Up to 96 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Any Grade 3 or higher 22 20 84
Grade 3 15 15 73
Grade 4 7 5 11
9.Secondary Outcome
Title Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations
Hide Description 3-level categorical of the worst of 1) premature treatment discontinuation, 2) temporary stop or 3) dose reduction. For Arm C, the worst for either PEG-IFN or RBV is summarized.
Time Frame Up to 96 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A and C participants. Arm B participants did not receive treatment.
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 0 169
Measure Type: Number
Unit of Measure: Participant
Premature treatment discontinuation 16 57
Temporarily off treatment 7 29
Reduced dose 2 33
10.Secondary Outcome
Title Number of Participants Adherent to Study Medications
Hide Description A categorical variable with levels adherent and non-adherent based on participants' self report. For Arm A, adherence was defined as not missing PEG within 2 weeks of visit. For Arm C, adherence was defined as not missing any PEG within 2 weeks of visit and not missing RBV within 4 days of visit.
Time Frame Arm A: at weeks 12, 24, 48 and 72. Arm C: at entry and weeks 12, 24, 48, 60.
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A and Arm C participants. Arm B participants did not receive treatment.
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 0 159
Measure Type: Number
Unit of Measure: Participant
Week 0: Number of participants with adherence data 0 158
Week 0: Number of participants adherent to meds NA [1]  132
Week 12:Number of participants with adherence data 37 150
Week 12:Number of participants adherent to meds 32 125
Week 24:Number of participants with adherence data 32 145
Week 24:Number of participants adherent to meds 28 118
Week 48:Number of participants with adherence data 22 120
Week 48:Number of participants adherent to meds 19 95
Week 60:Number of participants with adherence data 0 91
Week 60:Number of participants adherent to meds NA [1]  79
Week 72:Number of participants with adherence data 8 0
Week 72:Number of participants adherent to meds 7 NA [1] 
[1]
Evaluation not specified in protocol at this timepoint.
11.Secondary Outcome
Title HCV Polymorphisms
Hide Description Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued.
Time Frame Entry and week 72 (Arms A and B only).
Hide Outcome Measure Data
Hide Analysis Population Description
Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued. No participants were analyzed.
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title HCV-specific Immune Response in Intrahepatic Lymphocytes
Hide Description Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued.
Time Frame Entry and week 72 (Arms A and B only).
Hide Outcome Measure Data
Hide Analysis Population Description
Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued. No participants were analyzed.
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL)
Hide Description A blood sample was drawn to determine the HIV-1 viral load. HIV-1 viral load was categorized as <50 copies/mL (undetectable) or >=50 copies/mL (detectable). 50 is the lower limit of detection of the assay.
Time Frame Arms A and B: Weeks 0, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 48, 60, 72, 84
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B, and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Week 0: Number of participants with HIV RNA data 44 42 169
Week 0: No. of participants with undetectable VL 32 34 146
Week 12: Number of participants with HIV RNA data 0 0 164
Week 12: No. of participants with undetectable VL NA [1]  NA [1]  138
Week 24: Number of participants with HIV RNA data 39 39 165
Week 24: No. of participants with undetectable VL 25 25 141
Week 36: Number of participants with HIV RNA data 0 0 160
Week 36: No. of participants with undetectable VL NA [1]  NA [1]  134
Week 48: Number of participants with HIV RNA data 35 33 150
Week 48: No. of participants with undetectable VL 24 25 125
Week 60: Number of participants with HIV RNA data 0 0 140
Week 60: No. of participants with undetectable VL NA [1]  NA [1]  113
Week 72: Number of participants with HIV RNA data 27 27 140
Week 72: No. of participants with undetectable VL 19 20 107
Week 84: Number of participants with HIV RNA data 0 0 136
Week 84: No. of participants with undetectable VL NA [1]  NA [1]  108
[1]
Test not specified in protocol at this timepoint.
14.Secondary Outcome
Title Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Hide Description Insulin resistance was evaluated by HOMA-IR, calculated as [fasting glucose (mg/dL) x fasting insulin (uIU/mL)]/405. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting insulin and fasting glucose testing.
Time Frame Arms A and B: at entry and weeks 24, 48 and 72; Arm C: at entry and at weeks 12, 24, 36, 48, 72, 84 and 96.
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants who had HOMA-IR result available. In Arm C, metabolic testing was only performed on participants who enrolled under protocol version 1.0. The number of participants with results available at time points listed in the Time Frame are shown in the Data Table Row Titles below.
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 98
Median (Inter-Quartile Range)
Unit of Measure: mg/dL x uIU/mL
Week 0: HOMA-IR (N=32 in A, 32 in B, 72 in C)
3.84
(2.77 to 9.03)
2.49
(1.83 to 4.48)
2.37
(1.50 to 5.36)
Week 12: HOMA-IR (N=72 in C)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
2.47
(1.63 to 4.22)
Week 24: HOMA-IR (N=34 in A, 30 in B, 73 in C)
3.08
(1.68 to 5.59)
4.78
(1.78 to 6.13)
2.58
(1.35 to 4.44)
Week 36: HOMA-IR (N=66 in C)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
2.41
(1.44 to 4.58)
Week 48: HOMA-IR (N=30 in A, 24 in B, 74 in C)
3.53
(1.72 to 6.65)
2.84
(1.78 to 6.38)
3.25
(1.73 to 5.01)
Week 72: HOMA-IR (N=67 in C)
4.79
(3.41 to 7.83)
4.82
(2.46 to 9.12)
2.69
(1.66 to 5.47)
Week 84: HOMA-IR (N=63 in C)
NA [3] 
(NA to NA)
NA [3] 
(NA to NA)
2.99
(1.66 to 4.98)
Week 96: HOMA-IR (N=65 in C)
NA [4] 
(NA to NA)
NA [4] 
(NA to NA)
2.30
(1.63 to 4.15)
[1]
HOMA-IR was not collected at Week 12 in Arms A and B.
[2]
HOMA-IR was not collected at Week 36 in Arms A and B.
[3]
HOMA-IR was not collected at Week 84 in Arms A and B.
[4]
HOMA-IR was not collected at Week 96 in Arms A and B.
15.Secondary Outcome
Title Sustained Virologic Response
Hide Description Sustained Virologic Response (SVR) was defined as undetectable HCV viral load (<60 IU/ml) 24 weeks after treatment discontinuation.
Time Frame 24 weeks after end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Yes 0 0 88
No 44 42 81
16.Secondary Outcome
Title Number of Participants Who Used Antianorexia Agents, Such as Megestrol and Dronabinol
Hide Description Use of antianorexia agents, such as megestrol and dronabinol at any time after pre-assignment.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation..
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Number of participants who used megestrol 2 1 6
Number of participants who used dronabinol 4 4 22
17.Secondary Outcome
Title Number of Participants With Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF)
Hide Description Prescription as needed of hematologic adjuvant therapies: erythropoietin (EPO), granulocyte colony-stimulating factor (GCSF), and granulocyte-monocyte colony-stimulating factor (GM-CSF) any time after pre-assignment
Time Frame At any time after pre-assignment
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Measure Type: Number
Unit of Measure: Participant
Number of participants who used EPO 14 13 70
Number of participants who used GCSF 17 8 60
Number of participants who used GM-CSF 0 0 0
18.Secondary Outcome
Title Weight
Hide Description Participant weight in kilograms.
Time Frame Arms A and B: at entry and weeks 4, 8, 12, 16, 24, 32, 40, 48, 56, 64 and 72; Arm C: at entry and weeks 4, 8, 12, 16, 24, 36, 48, 72, 84 and 96.
Hide Outcome Measure Data
Hide Analysis Population Description
All Arm A, B and C participants who had weight available. The number of participants with results available at time points listed in the Time Frame are shown in the Data Table Row Titles below.
Arm/Group Title A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description:
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Overall Number of Participants Analyzed 44 42 169
Median (Inter-Quartile Range)
Unit of Measure: kilograms
Week 0: Weight (N=43 in A, 42 in B, 169 in C)
74.9
(67.6 to 86.8)
79.8
(69.7 to 88.3)
75.8
(68.6 to 84.4)
Week 4: Weight (N=43 in A, 35 in B, 161 in C)
74.7
(68.6 to 87.4)
80.4
(70.5 to 88.5)
75.8
(68.3 to 83.5)
Week 8: Weight (N=39 in A, 34 in B, 162 in C)
74.9
(66.7 to 87.3)
80.8
(71.8 to 90.9)
75.8
(67.6 to 84.9)
Week 12: Weight (N=42 in A, 30 in B, 157 in C)
76.3
(67.2 to 87.9)
81.1
(69.9 to 89.9)
76.3
(67.4 to 83.0)
Week 16: Weight (N=39 in A, 35 in B, 164 in C)
77.4
(67.9 to 89.5)
79.9
(70.0 to 90.4)
76.3
(66.3 to 83.2)
Week 24: Weight (N=39 in A, 36 in B, 165 in C)
75.5
(66.3 to 89.0)
79.4
(72.5 to 91.0)
75.8
(65.9 to 82.6)
Week 32: Weight (N=37 in A, 35 in B)
76.5
(69.0 to 88.1)
80.4
(70.8 to 87.7)
NA [1] 
(NA to NA)
Week 36: Weight (N=162 in C)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
75.0
(65.9 to 84.0)
Week 40: Weight (N=32 in A, 29 in B)
75.7
(67.7 to 86.4)
83.1
(70.9 to 91.0)
NA [3] 
(NA to NA)
Week 48: Weight (N=33 in A, 31 in B, 153 in C)
78.2
(68.8 to 88.7)
80.4
(68.1 to 93.3)
75.1
(66.3 to 84.4)
Week 56: Weight (N=31 in A, 24 in B)
79.7
(69.4 to 92.7)
81.6
(68.8 to 90.9)
NA [4] 
(NA to NA)
Week 64: Weight (N=26 in A, 24 in B)
78.5
(69.3 to 87.7)
84.0
(72.8 to 91.9)
NA [5] 
(NA to NA)
Week 72: Weight (N=26 in A, 27 in B, 141 in C)
81.6
(68.6 to 89.6)
85.4
(71.7 to 94.0)
75.6
(65.5 to 84.6)
Week 84: Weight (N=140 in C)
NA [6] 
(NA to NA)
NA [6] 
(NA to NA)
77.0
(67.6 to 87.6)
Week 96: Weight (N=138)
NA [7] 
(NA to NA)
NA [7] 
(NA to NA)
78.4
(69.6 to 88.0)
[1]
Weight was not collected at Week 32 in Arm C.
[2]
Weight was not collected at Week 36 in Arms A and B.
[3]
Weight was not collected at Week 40 in Arm C.
[4]
Weight was not collected at Week 56 in Arm C.
[5]
Weight was not collected at Week 64 in Arm C.
[6]
Weight was not collected at Week 84 in Arms A and B.
[7]
Weight was not collected at Week 96 in Arms A and B.
Time Frame From entry (Step 2 for Arms A and B, Step 3 for Arm C) to study completion (at Week 72 for Step 2; at week 78-84 for Step 3, depending on participants' time in Step 1).
Adverse Event Reporting Description The protocol required reporting of signs/symptoms and laboratory results >=Grade 3 and events that led to a change in treatment, regardless of grade. Hemoglobin, plateles, ANC, fasting HDL, LDL and total cholesterol, insulin and glucose values were reported regardless of grade. The DAIDS AE Grading Table (1992) and Expedited AE Manual (2004) were used.
 
Arm/Group Title Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) OL (PEG-IFN, RBV) Then OL Randomized (Observation) OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Hide Arm/Group Description At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm. At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm. At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & ribavirin [RBV] 1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.
All-Cause Mortality
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) OL (PEG-IFN, RBV) Then OL Randomized (Observation) OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) OL (PEG-IFN, RBV) Then OL Randomized (Observation) OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/44 (13.64%)   2/42 (4.76%)   37/169 (21.89%) 
Blood and lymphatic system disorders       
Anaemia  1  1/44 (2.27%)  0/42 (0.00%)  2/169 (1.18%) 
Bone marrow failure  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Neutropenia  1  2/44 (4.55%)  0/42 (0.00%)  13/169 (7.69%) 
Thrombocytopenia  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Cardiac disorders       
Cardiac arrest  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Coronary artery disease  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Myocardial infarction  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Endocrine disorders       
Basedow's disease  1  0/44 (0.00%)  1/42 (2.38%)  0/169 (0.00%) 
Hypothyroidism  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Gastrointestinal disorders       
Abdominal pain  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Pancreatitis  1  0/44 (0.00%)  0/42 (0.00%)  2/169 (1.18%) 
General disorders       
Death  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Pyrexia  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Infections and infestations       
Pneumonia  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Injury, poisoning and procedural complications       
Overdose  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Investigations       
Blood triglycerides increased  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Electrocardiogram QT prolonged  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Haemoglobin decreased  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Neutrophil count  1  1/44 (2.27%)  1/42 (2.38%)  0/169 (0.00%) 
Neutrophil count decreased  1  1/44 (2.27%)  1/42 (2.38%)  3/169 (1.78%) 
Metabolism and nutrition disorders       
Hyperglycaemia  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Hypertriglyceridaemia  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cerebellar tumour  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Lung neoplasm malignant  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Lymphoma  1  1/44 (2.27%)  0/42 (0.00%)  0/169 (0.00%) 
Neoplasm  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Prostate cancer  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Squamous cell carcinoma  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Psychiatric disorders       
Abnormal dreams  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  1/44 (2.27%)  0/42 (0.00%)  0/169 (0.00%) 
Pulmonary embolism  1  0/44 (0.00%)  0/42 (0.00%)  1/169 (0.59%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) OL (PEG-IFN, RBV) Then OL Randomized (Observation) OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   43/44 (97.73%)   41/42 (97.62%)   166/169 (98.22%) 
General disorders       
Chest pain  1  4/44 (9.09%)  0/42 (0.00%)  8/169 (4.73%) 
Fatigue  1  4/44 (9.09%)  0/42 (0.00%)  14/169 (8.28%) 
Pyrexia  1  2/44 (4.55%)  1/42 (2.38%)  11/169 (6.51%) 
Infections and infestations       
Bronchitis  1  2/44 (4.55%)  0/42 (0.00%)  9/169 (5.33%) 
Investigations       
Activated partial thromboplastin time prolonged  1  8/44 (18.18%)  8/42 (19.05%)  1/169 (0.59%) 
Alanine aminotransferase increased  1  30/44 (68.18%)  32/42 (76.19%)  64/169 (37.87%) 
Aspartate aminotransferase increased  1  7/44 (15.91%)  6/42 (14.29%)  12/169 (7.10%) 
Blood bilirubin increased  1  2/44 (4.55%)  0/42 (0.00%)  19/169 (11.24%) 
Blood glucose abnormal  1  14/44 (31.82%)  8/42 (19.05%)  55/169 (32.54%) 
Blood glucose decreased  1  3/44 (6.82%)  2/42 (4.76%)  14/169 (8.28%) 
Blood glucose increased  1  11/44 (25.00%)  7/42 (16.67%)  16/169 (9.47%) 
Blood triglycerides abnormal  1  6/44 (13.64%)  0/42 (0.00%)  22/169 (13.02%) 
Blood uric acid increased  1  1/44 (2.27%)  1/42 (2.38%)  11/169 (6.51%) 
Gamma-glutamyltransferase increased  1  8/44 (18.18%)  2/42 (4.76%)  6/169 (3.55%) 
Haemoglobin decreased  1  5/44 (11.36%)  1/42 (2.38%)  22/169 (13.02%) 
Lipase increased  1  5/44 (11.36%)  6/42 (14.29%)  13/169 (7.69%) 
Neutrophil count decreased  1  37/44 (84.09%)  25/42 (59.52%)  144/169 (85.21%) 
Platelet count decreased  1  21/44 (47.73%)  9/42 (21.43%)  58/169 (34.32%) 
Prothrombin time prolonged  1  5/44 (11.36%)  4/42 (9.52%)  0/169 (0.00%) 
Weight decreased  1  2/44 (4.55%)  2/42 (4.76%)  10/169 (5.92%) 
Psychiatric disorders       
Depression  1  3/44 (6.82%)  2/42 (4.76%)  13/169 (7.69%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  2/44 (4.55%)  1/42 (2.38%)  13/169 (7.69%) 
Vascular disorders       
Hypertension  1  4/44 (9.09%)  1/42 (2.38%)  4/169 (2.37%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve US or foreign patent or other intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
EMail: ACTGCT.Gov@s-3.com
Other Publications:
The Division of AIDS Table for Grading the Severity of Adult Adverse Events (DAIDS AE Grading Table), August 1992.
Manual for Expedited Reporting of Adverse Events to Division of AIDS (DAIDS EAE Manual), May 2004.
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00078403     History of Changes
Other Study ID Numbers: A5178
10008 ( Registry Identifier: DAIDS ES Registry Number )
First Submitted: February 24, 2004
First Posted: February 25, 2004
Results First Submitted: November 5, 2010
Results First Posted: April 27, 2011
Last Update Posted: January 27, 2017