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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00078403
First received: February 24, 2004
Last updated: November 30, 2016
Last verified: November 2016
Results First Received: November 5, 2010  
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

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
People with hepatitis C virus (HCV)/HIV coinfection were recruited for participation in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Participant Flow:   Overall Study
    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)
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).



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants.

Reporting Groups
  Description
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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 Total of all reporting groups

Baseline Measures
   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 
Overall Participants Analyzed 
[Units: Participants]
 44   42   169   255 
Age 
[Units: Participants]
Count of 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 
[Units: Years]
Mean (Standard Deviation)
 48.8  (6.7)   48.1  (5.8)   47.2  (7.1)   47.6  (6.8) 
Gender 
[Units: Participants]
Count of 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 
[Units: Participants]
       
United States   41   40   168   249 
Puerto Rico   3   2   1   6 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS)   [ Time Frame: Baseline and at week 72 or premature discontinuation ]

Measure Type Primary
Measure Title Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS)
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 33   29   0 
Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS) 
[Units: Metavir units per one year (52 weeks)]
Median (Inter-Quartile Range)
 0 
 (0 to 1.37) 
 0 
 (0 to 2) 
  


Statistical Analysis 1 for Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS)
Groups [1] A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) vs. B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Exact Wilcoxon rank sum test
P Value [4] 0.58
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.



2.  Secondary:   Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)   [ Time Frame: Arms A and B: Weeks 0, 12, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 60, 72, 84 ]

Measure Type Secondary
Measure Title Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL) 
[Units: 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.

No statistical analysis provided for Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)



3.  Secondary:   Time-scaled Change in Ishak Liver Inflammation Score (SCIIS)   [ Time Frame: Baseline and at week 72 or premature discontinuation ]

Measure Type Secondary
Measure Title Time-scaled Change in Ishak Liver Inflammation Score (SCIIS)
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCIIS available (Complete Cases)

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   0 
Time-scaled Change in Ishak Liver Inflammation Score (SCIIS) 
[Units: Ishak units per one year (52 weeks)]
Median (Inter-Quartile Range)
 0 
 (-0.75 to 1.79) 
 1.31 
 (0 to 2.10) 
  

No statistical analysis provided for Time-scaled Change in Ishak Liver Inflammation Score (SCIIS)



4.  Secondary:   Number of Participants With Anemia   [ Time Frame: Up to 96 weeks ]

Measure Type Secondary
Measure Title Number of Participants With Anemia
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With Anemia 
[Units: Participant]
     
Anemia >= Grade 2   1   0   6 
Grade 2   0   0   3 
Grade 3   0   0   1 
Grade 4   1   0   2 

No statistical analysis provided for Number of Participants With Anemia



5.  Secondary:   Number of Participants With Neutropenia   [ Time Frame: Up to 96 weeks ]

Measure Type Secondary
Measure Title Number of Participants With Neutropenia
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With Neutropenia 
[Units: Participant]
     
Neutropenia >= Grade 2   20   10   96 
Grade 2   7   4   38 
Grade 3   10   5   37 
Grade 4   3   1   21 

No statistical analysis provided for Number of Participants With Neutropenia



6.  Secondary:   Number of Participants With Thrombocytopenia   [ Time Frame: Up to 96 weeks ]

Measure Type Secondary
Measure Title Number of Participants With Thrombocytopenia
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With Thrombocytopenia 
[Units: Participant]
     
Thrombocytopenia >= Grade 2   14   4   31 
Grade 2   10   3   25 
Grade 3   4   1   5 
Grade 4   0   0   1 

No statistical analysis provided for Number of Participants With Thrombocytopenia



7.  Secondary:   Number of Participants With Depression and/or Other Psychological Events   [ Time Frame: Up to 96 weeks ]

Measure Type Secondary
Measure Title Number of Participants With Depression and/or Other Psychological Events
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With Depression and/or Other Psychological Events 
[Units: Participant]
     
Any psychological   3   1   19 
Grade 3   2   1   18 
Grade 4   1   0   1 

No statistical analysis provided for Number of Participants With Depression and/or Other Psychological Events



8.  Secondary:   Number of Participants With High-grade Signs and Symptoms or Laboratory Values   [ Time Frame: Up to 96 Weeks ]

Measure Type Secondary
Measure Title Number of Participants With High-grade Signs and Symptoms or Laboratory Values
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With High-grade Signs and Symptoms or Laboratory Values 
[Units: Participant]
     
Any Grade 3 or higher   22   20   84 
Grade 3   15   15   73 
Grade 4   7   5   11 

No statistical analysis provided for Number of Participants With High-grade Signs and Symptoms or Laboratory Values



9.  Secondary:   Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations   [ Time Frame: Up to 96 Weeks ]

Measure Type Secondary
Measure Title Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A and C participants. Arm B participants did not receive treatment.

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   0   169 
Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations 
[Units: Participant]
     
Premature treatment discontinuation   16      57 
Temporarily off treatment   7      29 
Reduced dose   2      33 

No statistical analysis provided for Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations



10.  Secondary:   Number of Participants Adherent to Study Medications   [ Time Frame: Arm A: at weeks 12, 24, 48 and 72. Arm C: at entry and weeks 12, 24, 48, 60. ]

Measure Type Secondary
Measure Title Number of Participants Adherent to Study Medications
Measure 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.  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A and Arm C participants. Arm B participants did not receive treatment.

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   0   159 
Number of Participants Adherent to Study Medications 
[Units: 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.

No statistical analysis provided for Number of Participants Adherent to Study Medications



11.  Secondary:   HCV Polymorphisms   [ Time Frame: Entry and week 72 (Arms A and B only). ]

Measure Type Secondary
Measure Title HCV Polymorphisms
Measure 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).  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).

Measured Values
   A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)   B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 
Participants Analyzed 
[Units: Participants]
 0   0 
HCV Polymorphisms       

No statistical analysis provided for HCV Polymorphisms



12.  Secondary:   HCV-specific Immune Response in Intrahepatic Lymphocytes   [ Time Frame: Entry and week 72 (Arms A and B only). ]

Measure Type Secondary
Measure Title HCV-specific Immune Response in Intrahepatic Lymphocytes
Measure 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).  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).

Measured Values
   A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)   B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 
Participants Analyzed 
[Units: Participants]
 0   0 
HCV-specific Immune Response in Intrahepatic Lymphocytes       

No statistical analysis provided for HCV-specific Immune Response in Intrahepatic Lymphocytes



13.  Secondary:   Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL)   [ Time Frame: Arms A and B: Weeks 0, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 48, 60, 72, 84 ]

Measure Type Secondary
Measure Title Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL)
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B, and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL) 
[Units: 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.

No statistical analysis provided for Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL)



14.  Secondary:   Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)   [ 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. ]

Measure Type Secondary
Measure Title Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Measure 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.  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   98 
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) 
[Units: mg/dL x uIU/mL]
Median (Inter-Quartile Range)
     
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 [1]   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 [2]   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 [3]   2.99 
 (1.66 to 4.98) 
Week 96: HOMA-IR (N=65 in C)   NA [4]   NA [4]   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.

No statistical analysis provided for Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)



15.  Secondary:   Sustained Virologic Response   [ Time Frame: 24 weeks after end of treatment ]

Measure Type Secondary
Measure Title Sustained Virologic Response
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Sustained Virologic Response 
[Units: Participant]
     
Yes   0   0   88 
No   44   42   81 

No statistical analysis provided for Sustained Virologic Response



16.  Secondary:   Number of Participants Who Used Antianorexia Agents, Such as Megestrol and Dronabinol   [ Time Frame: Up to 96 weeks ]

Measure Type Secondary
Measure Title Number of Participants Who Used Antianorexia Agents, Such as Megestrol and Dronabinol
Measure Description Use of antianorexia agents, such as megestrol and dronabinol at any time after pre-assignment.
Time Frame Up to 96 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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..

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants Who Used Antianorexia Agents, Such as Megestrol and Dronabinol 
[Units: Participant]
     
Number of participants who used megestrol   2   1   6 
Number of participants who used dronabinol   4   4   22 

No statistical analysis provided for Number of Participants Who Used Antianorexia Agents, Such as Megestrol and Dronabinol



17.  Secondary:   Number of Participants With Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF)   [ Time Frame: At any time after pre-assignment ]

Measure Type Secondary
Measure Title Number of Participants With Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF)
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Number of Participants With Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF) 
[Units: 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 

No statistical analysis provided for Number of Participants With Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF)



18.  Secondary:   Weight   [ 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. ]

Measure Type Secondary
Measure Title Weight
Measure 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.  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) 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.
B: OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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).
C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

Measured Values
   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) 
Participants Analyzed 
[Units: Participants]
 44   42   169 
Weight 
[Units: Kilograms]
Median (Inter-Quartile Range)
     
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] 
Week 36: Weight (N=162 in C)   NA [2]   NA [2]   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] 
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] 
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] 
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 [6]   77.0 
 (67.6 to 87.6) 
Week 96: Weight (N=138)   NA [7]   NA [7]   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.

No statistical analysis provided for Weight




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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com


Publications of Results:
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 )
Study First Received: February 24, 2004
Results First Received: November 5, 2010
Last Updated: November 30, 2016