Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00665353
First received: April 22, 2008
Last updated: May 14, 2013
Last verified: May 2013
Results First Received: June 7, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV-1 and Hepatitis C Co-Infection
Interventions: Drug: pioglitazone
Drug: peginterferon
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
Subjects were enrolled at 8 ACTG sites. The dates of first and last study enrollments were March 31, 2009 and May 26, 2010, respectively.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A5239 was a single-arm study which enrolled prior nonresponders to peginterferon (PEG-IFN) and ribavirin (RBV) > therapy with documented insulin resistance. 31 potential subjects failed to meet all inclusion/exclusion criteria. 22 of these potential subjects did not meet the HOMA-IR criterion (> 2.5 within 42 days prior to study entry).

Reporting Groups
  Description
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2) All participants in Step 1 received pioglitazone therapy for 24 to 28 weeks. Participants continued pioglitazone and add peginterferon and ribavirin to their treatment regimen for up to 48 additional weeks in Step 2.

Participant Flow for 2 periods

Period 1:   Study Step 1
    PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)  
STARTED     19  
COMPLETED     16  
NOT COMPLETED     3  
Adverse Event                 1  
Withdrawal by Subject                 2  

Period 2:   Study Step 2
    PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)  
STARTED     16  
COMPLETED     2  
NOT COMPLETED     14  
Lost to Follow-up                 2  
Lack of Efficacy                 12  



  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.
No text entered.

Reporting Groups
  Description
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2) All participants in Step 1 received pioglitazone therapy for 24 to 28 weeks. Participants continued pioglitazone and add peginterferon and ribavirin to their treatment regimen for up to 48 additional weeks in Step 2.

Baseline Measures
    PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)  
Number of Participants  
[units: participants]
  19  
Age  
[units: years]
Mean ± Standard Deviation
  49  ± 7  
Gender  
[units: participants]
 
Female     3  
Male     16  
Race/Ethnicity, Customized [1]
[units: participants]
 
White non-Hispanic     8  
Black non-Hispanic     9  
Hispanic (regardless of race)     2  
Region of Enrollment  
[units: participants]
 
United States     19  
Age categorical  
[units: participants]
 
30 - 39 years     1  
40 - 49 years     9  
50 - 59 years     8  
60 - 69 years     1  
IV drug history [2]
[units: participants]
 
Never     7  
Previously     12  
Body Mass Index (BMI) [3]
[units: kg/m^2]
Mean ± Standard Deviation
  27.7  ± 4.1  
HIV-1 RNA  
[units: participants]
 
< 50 copies/mL     15  
50 - 99 copies/mL     2  
100 - 499 copies/mL     2  
CD4 count  
[units: cells/mm^3]
Mean ± Standard Deviation
  567  ± 192  
Nadir CD4 count  
[units: participants]
 
<= 50 cells/mm^3     4  
51 - 100 cells/mm^3     4  
101 - 200 cells/mm^3     4  
201 - 500 cells/mm^3     6  
> 500 cells/mm^3     1  
Thyrotropin [4]
[units: mIU/L]
Mean ± Standard Deviation
  1.49  ± 0.67  
Hemoglobin  
[units: g/dL]
Mean ± Standard Deviation
  14.4  ± 1.5  
Absolute neutrophil count  
[units: cells/mm^3]
Mean ± Standard Deviation
  2501  ± 1031  
Platelets  
[units: cells/mm^3]
Mean ± Standard Deviation
  185842  ± 67375  
Direct bilirubin  
[units: * ULN]
Mean ± Standard Deviation
  1.0  ± 0.6  
Alanine Aminotransferase (ALT)  
[units: * ULN]
Mean ± Standard Deviation
  1.4  ± 1.2  
Aspartate Aminotransferase (AST)  
[units: * ULN]
Mean ± Standard Deviation
  1.5  ± 0.9  
Gamma-glutamyl transferase [5]
[units: U/L]
Mean ± Standard Deviation
  154  ± 127  
Fasting glucose  
[units: mg/dL]
Mean ± Standard Deviation
  100  ± 12  
Fasting insulin  
[units: mIU/L]
Mean ± Standard Deviation
  25  ± 13  
Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)  
[units: mg/dL x mIU/L / 405]
Mean ± Standard Deviation
  6.3  ± 3.5  
Prior hepatitis C virus (HCV) non-response type  
[units: participants]
 
< 2 log10 drop AND detectable >= 10 and < 22 weeks     13  
Detectable after >= 22 and < 30 weeks     6  
[1] Derived from self-reported race and ethnicity.
[2] Self-reported
[3] Body Mass Index (weight in kilograms divided by height in meters squared)
[4] N=17, 2 were missing results
[5] N=14, 5 had missing results.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 24 of Step 2.   [ Time Frame: Week 24 of Step 2 ]

2.  Secondary:   Safety and Tolerability   [ Time Frame: Step 1 (Up to 24 to 28 weeks) ]

3.  Secondary:   Safety and Tolerability   [ Time Frame: Step 2 (Up to 72 weeks) ]

4.  Secondary:   The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 72of Step 2.   [ Time Frame: Week 72 of Step 2 ]

5.  Secondary:   Absolute Change From Entry to Week 24 of Step 1 in AST and ALT.   [ Time Frame: From Entry to Week 24 of Step 1 ]

6.  Secondary:   Absolute Change From Entry to Week 24 of Step 1 in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)   [ Time Frame: From Entry to Week 24 of Step 1 ]

7.  Secondary:   Absolute Change From Entry to Week 24 of Step 1 in Fasting Total Cholesterol and Triglycerides.   [ Time Frame: From Entry to Week 24 of Step 1 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study did not fully enroll and the small sample size precluded subgroup analysis.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: 617-432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu


Publications:

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00665353     History of Changes
Obsolete Identifiers: NCT00735982
Other Study ID Numbers: ACTG A5239, 1U01AI068636
Study First Received: April 22, 2008
Results First Received: June 7, 2012
Last Updated: May 14, 2013
Health Authority: United States: Federal Government