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: August 13, 2014
Last verified: August 2014
Results First Received: November 5, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV Infections
Hepatitis C
Liver Disease
Interventions: Drug: Peginterferon alfa-2a
Drug: Ribavirin

  Participant Flow
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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 subjects 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 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.
OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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.
OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.

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

Reporting Groups
  Description
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 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.
OL (PEG-IFN, RBV) Then OL Randomized (Observation) 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.
OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) 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.
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  
Number of Participants  
[units: participants]
  44     42     169     255  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     44     42     169     255  
>=65 years     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]
       
Female     12     12     19     43  
Male     32     30     150     212  
Region of Enrollment  
[units: participants]
       
United States     41     40     168     249  
Puerto Rico     3     2     1     6  



  Outcome Measures
  Show All Outcome Measures

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

2.  Secondary:   Number of Participants With Detectable HCV RNA 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 ]

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

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

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

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

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

8.  Secondary:   Other High-grade Signs and Symptoms and Laboratory Values   [ Time Frame: Up to 96 Weeks ]
  Hide Outcome Measure 8

Measure Type Secondary
Measure Title Other High-grade Signs and Symptoms and Laboratory Values
Measure Description Number of participants with “Other high-grade signs and symptoms and 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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 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.
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 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.
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 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 & RBV1-1.2 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.

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

No statistical analysis provided for Other High-grade Signs and Symptoms and Laboratory Values



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

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. ]

11.  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 ]

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

13.  Secondary:   Use of Antianorexia Agents, Such as Megestrol and Dronabinol   [ Time Frame: Up to 96 weeks ]

14.  Secondary:   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 ]

15.  Secondary:   Symptom Distress   [ Time Frame: Arms A and B: at entry and weeks 12, 24, 48 and 72. Arm C: at entry and weeks 12, 24, 48, 60, 84. ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

16.  Secondary:   Quality of Life   [ Time Frame: Arms A and B: at entry and weeks 12, 24, 48 and 72. Arm C: at entry and weeks 12, 24, 48, 60, 84. ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

17.  Secondary:   HCV Polymorphisms   [ Time Frame: Entry and week 72 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

18.  Secondary:   HCV-specific Immune Response in Intrahepatic Lymphocytes   [ Time Frame: Entry and week 72 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

19.  Secondary:   Noninvasive Measures of Liver Fibrosis, Including Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Bilirubin, Albumin, and Protein Measurements   [ Time Frame: Entry and week 72 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

20.  Secondary:   Metabolic Parameters Including Insulin Resistance, Defined as Fasting Glucose, and Weight.   [ Time Frame: Weight: throughout study. Metabolic parameters: Arms A and B: entry and weeks 24, 48 and 72; Arm C: at entry and at weeks 12, 24, 36, 48, 60, 72 and 84. ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
No text entered.


  More Information
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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: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School
e-mail: sdac.ct.gov@sdac.harvard.edu


Publications of Results:
Other Publications:

Publications automatically indexed to this study:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00078403     History of Changes
Other Study ID Numbers: A5178, 10008
Study First Received: February 24, 2004
Results First Received: November 5, 2010
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration