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Trial record 1 of 3 for:    15282351 [PUBMED-IDS]
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Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance

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ClinicalTrials.gov Identifier: NCT00665353
Recruitment Status : Completed
First Posted : April 23, 2008
Results First Posted : September 13, 2012
Last Update Posted : October 12, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 and Hepatitis C Co-Infection
Interventions Drug: pioglitazone
Drug: peginterferon
Drug: ribavirin
Enrollment 19
Recruitment Details 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 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).
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description 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.
Period Title: Study Step 1
Started 19
Completed 16
Not Completed 3
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             2
Period Title: Study Step 2
Started 16
Completed 2
Not Completed 14
Reason Not Completed
Lost to Follow-up             2
Lack of Efficacy             12
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants
49  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
3
  15.8%
Male
16
  84.2%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
White non-Hispanic 8
Black non-Hispanic 9
Hispanic (regardless of race) 2
[1]
Measure Description: Derived from self-reported race and ethnicity.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
Age categorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
30 - 39 years 1
40 - 49 years 9
50 - 59 years 8
60 - 69 years 1
IV drug history   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
Never 7
Previously 12
[1]
Measure Description: Self-reported
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 19 participants
27.7  (4.1)
[1]
Measure Description: Body Mass Index (weight in kilograms divided by height in meters squared)
HIV-1 RNA  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
< 50 copies/mL 15
50 - 99 copies/mL 2
100 - 499 copies/mL 2
CD4 count  
Mean (Standard Deviation)
Unit of measure:  Cells/mm^3
Number Analyzed 19 participants
567  (192)
Nadir CD4 count  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 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   [1] 
Mean (Standard Deviation)
Unit of measure:  mIU/L
Number Analyzed 19 participants
1.49  (0.67)
[1]
Measure Description: N=17, 2 were missing results
Hemoglobin  
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 19 participants
14.4  (1.5)
Absolute neutrophil count  
Mean (Standard Deviation)
Unit of measure:  Cells/mm^3
Number Analyzed 19 participants
2501  (1031)
Platelets  
Mean (Standard Deviation)
Unit of measure:  Cells/mm^3
Number Analyzed 19 participants
185842  (67375)
Direct bilirubin  
Mean (Standard Deviation)
Unit of measure:  * ULN
Number Analyzed 19 participants
1.0  (0.6)
Alanine Aminotransferase (ALT)  
Mean (Standard Deviation)
Unit of measure:  * ULN
Number Analyzed 19 participants
1.4  (1.2)
Aspartate Aminotransferase (AST)  
Mean (Standard Deviation)
Unit of measure:  * ULN
Number Analyzed 19 participants
1.5  (0.9)
Gamma-glutamyl transferase   [1] 
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 19 participants
154  (127)
[1]
Measure Description: N=14, 5 had missing results.
Fasting glucose  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 19 participants
100  (12)
Fasting insulin  
Mean (Standard Deviation)
Unit of measure:  mIU/L
Number Analyzed 19 participants
25  (13)
Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)  
Mean (Standard Deviation)
Unit of measure:  mg/dL x mIU/L / 405
Number Analyzed 19 participants
6.3  (3.5)
Prior hepatitis C virus (HCV) non-response type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
< 2 log10 drop AND detectable >= 10 and < 22 weeks 13
Detectable after >= 22 and < 30 weeks 6
1.Primary Outcome
Title The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 24 of Step 2.
Hide Description [Not Specified]
Time Frame Week 24 of Step 2
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled subjects.
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.158
(0.059 to 1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Comments The proportion of subjects responding was compared to a historical null rate of 0.10. The hypothesized response rate was 0.30.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments This is an unadjusted p-value. Statistical significance was defined a priori as 0.10.
Method Exact test of proportions
Comments [Not Specified]
Method of Estimation Estimation Parameter proportion
Estimated Value 0.158
Confidence Interval (1-Sided) 90%
0.059
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Safety and Tolerability
Hide Description Summary of the number of subjects with at least one grade 3 or higher sign/symptom or laboratory abnormality.
Time Frame Step 1 (Up to 24 to 28 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled subjects.
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: participants
7
3.Secondary Outcome
Title Safety and Tolerability
Hide Description Summary of the number of subjects with at least one grade 3 or higher sign/symptom or laboratory abnormality.
Time Frame Step 2 (Up to 72 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All subject enrolled in Step 2.
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: participants
13
4.Secondary Outcome
Title The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 72of Step 2.
Hide Description [Not Specified]
Time Frame Week 72 of Step 2
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled subjects.
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.053
(0.001 to 1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Comments The proportion of subjects responding was compared to a historical null rate of 0.02. The hypothesized response rate was 0.15.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments This is an unadjusted p-value. Statistical significance was defined a priori as 0.10.
Method Exact test of proportions
Comments [Not Specified]
Method of Estimation Estimation Parameter proportion
Estimated Value 0.053
Confidence Interval (1-Sided) 90%
0.001
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Absolute Change From Entry to Week 24 of Step 1 in AST and ALT.
Hide Description [Not Specified]
Time Frame From Entry to Week 24 of Step 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with both Entry and Week 24 LFT results.
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 17
Median (Inter-Quartile Range)
Unit of Measure: x ULN
24 week change in ALT (n=17)
-0.14
(-0.47 to 0.02)
24 week change in AST (n=17)
-0.20
(-0.29 to -0.08)
6.Secondary Outcome
Title Absolute Change From Entry to Week 24 of Step 1 in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)
Hide Description [Not Specified]
Time Frame From Entry to Week 24 of Step 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with both Entry and Week 24 HOMA-IR results.
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 16
Median (Inter-Quartile Range)
Unit of Measure: mg/dL x uIU/mL / 405
-1.2
(-3.6 to 0.9)
7.Secondary Outcome
Title Absolute Change From Entry to Week 24 of Step 1 in Fasting Total Cholesterol and Triglycerides.
Hide Description [Not Specified]
Time Frame From Entry to Week 24 of Step 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with both Entry and Week 24 fasting lipid results.
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 16
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
24 week change in total cholesterol (n=16)
5.5
(-2.0 to 20.5)
24 week change in triglycerides (n=16)
28.5
(-15.5 to 73.0)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Hide Arm/Group Description 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.
All-Cause Mortality
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Affected / at Risk (%)
Total   2/19 (10.53%) 
Gastrointestinal disorders   
Pancreatitis  1  1/19 (5.26%) 
Infections and infestations   
Pneumocystis jiroveci pneumonia  1  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Pneumonia aspiration  1  1/19 (5.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Affected / at Risk (%)
Total   18/19 (94.74%) 
Blood and lymphatic system disorders   
Neutropenia  1  2/19 (10.53%) 
Thrombocytopenia  1  1/19 (5.26%) 
Eye disorders   
Eye pain  1  1/19 (5.26%) 
Glaucoma  1  1/19 (5.26%) 
Gastrointestinal disorders   
Abdominal pain  1  2/19 (10.53%) 
Cheilitis  1  1/19 (5.26%) 
Constipation  1  2/19 (10.53%) 
Diarrhoea  1  2/19 (10.53%) 
Dry mouth  1  1/19 (5.26%) 
Epiploic appendagitis  1  1/19 (5.26%) 
Flatulence  1  1/19 (5.26%) 
Gastrooesophageal reflux disease  1  1/19 (5.26%) 
Leukoplakia oral  1  1/19 (5.26%) 
Mouth ulceration  1  1/19 (5.26%) 
Nausea  1  1/19 (5.26%) 
Oral discomfort  1  1/19 (5.26%) 
Oral pain  1  1/19 (5.26%) 
Vomiting  1  2/19 (10.53%) 
General disorders   
Asthenia  1  3/19 (15.79%) 
Chest discomfort  1  1/19 (5.26%) 
Chest pain  1  1/19 (5.26%) 
Chills  1  1/19 (5.26%) 
Fatigue  1  6/19 (31.58%) 
Irritability  1  1/19 (5.26%) 
Malaise  1  1/19 (5.26%) 
Pain  1  1/19 (5.26%) 
Pyrexia  1  2/19 (10.53%) 
Hepatobiliary disorders   
Hepatitis  1  1/19 (5.26%) 
Infections and infestations   
Acute sinusitis  1  1/19 (5.26%) 
Bartholin's abscess  1  1/19 (5.26%) 
Bronchitis  1  1/19 (5.26%) 
Folliculitis  1  1/19 (5.26%) 
Gastroenteritis viral  1  1/19 (5.26%) 
Herpes zoster  1  3/19 (15.79%) 
Oesophageal candidiasis  1  1/19 (5.26%) 
Oral candidiasis  1  1/19 (5.26%) 
Pneumonia bacterial  1  1/19 (5.26%) 
Sinusitis  1  1/19 (5.26%) 
Upper respiratory tract infection  1  3/19 (15.79%) 
Urinary tract infection  1  1/19 (5.26%) 
Injury, poisoning and procedural complications   
Excoriation  1  1/19 (5.26%) 
Thermal burn  1  1/19 (5.26%) 
Investigations   
Alanine aminotransferase increased  1  13/19 (68.42%) 
Aspartate aminotransferase increased  1  16/19 (84.21%) 
Blood albumin abnormal  1  1/19 (5.26%) 
Blood alkaline phosphatase increased  1  3/19 (15.79%) 
Blood bicarbonate abnormal  1  4/19 (21.05%) 
Blood bilirubin increased  1  3/19 (15.79%) 
Blood creatinine increased  1  1/19 (5.26%) 
Blood glucose abnormal  1  11/19 (57.89%) 
Blood glucose decreased  1  1/19 (5.26%) 
Blood glucose increased  1  3/19 (15.79%) 
Blood phosphorus decreased  1  2/19 (10.53%) 
Blood sodium decreased  1  1/19 (5.26%) 
Haemoglobin decreased  1  7/19 (36.84%) 
Lipase abnormal  1  1/19 (5.26%) 
Lipase increased  1  4/19 (21.05%) 
Neutrophil count decreased  1  12/19 (63.16%) 
Platelet count decreased  1  12/19 (63.16%) 
Weight decreased  1  1/19 (5.26%) 
White blood cell count decreased  1  3/19 (15.79%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/19 (5.26%) 
Vitamin D deficiency  1  1/19 (5.26%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  7/19 (36.84%) 
Flank pain  1  1/19 (5.26%) 
Musculoskeletal stiffness  1  1/19 (5.26%) 
Myalgia  1  4/19 (21.05%) 
Pain in extremity  1  2/19 (10.53%) 
Nervous system disorders   
Cervicobrachial syndrome  1  1/19 (5.26%) 
Cognitive disorder  1  1/19 (5.26%) 
Disturbance in attention  1  1/19 (5.26%) 
Dizziness  1  1/19 (5.26%) 
Hypoaesthesia  1  1/19 (5.26%) 
Mental impairment  1  1/19 (5.26%) 
Neuralgia  1  1/19 (5.26%) 
Paraesthesia  1  1/19 (5.26%) 
Sinus headache  1  1/19 (5.26%) 
Psychiatric disorders   
Abnormal dreams  1  1/19 (5.26%) 
Affective disorder  1  1/19 (5.26%) 
Anger  1  1/19 (5.26%) 
Anhedonia  1  1/19 (5.26%) 
Anxiety  1  3/19 (15.79%) 
Depression  1  3/19 (15.79%) 
Depressive symptom  1  1/19 (5.26%) 
Insomnia  1  4/19 (21.05%) 
Renal and urinary disorders   
Dysuria  1  1/19 (5.26%) 
Renal failure acute  1  1/19 (5.26%) 
Reproductive system and breast disorders   
Erectile dysfunction  1  1/19 (5.26%) 
Vulvovaginal pain  1  1/19 (5.26%) 
Vulvovaginal swelling  1  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/19 (10.53%) 
Dyspnoea  1  1/19 (5.26%) 
Nasal congestion  1  1/19 (5.26%) 
Oropharyngeal pain  1  1/19 (5.26%) 
Pharyngeal oedema  1  1/19 (5.26%) 
Respiratory tract congestion  1  2/19 (10.53%) 
Sinus congestion  1  1/19 (5.26%) 
Wheezing  1  1/19 (5.26%) 
Skin and subcutaneous tissue disorders   
Dermatitis contact  1  1/19 (5.26%) 
Pain of skin  1  1/19 (5.26%) 
Rash  1  1/19 (5.26%) 
Skin lesion  1  1/19 (5.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
The study did not fully enroll and the small sample size precluded subgroup analysis.
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
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
Layout table for additonal information
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00665353     History of Changes
Obsolete Identifiers: NCT00735982
Other Study ID Numbers: ACTG A5239
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: April 22, 2008
First Posted: April 23, 2008
Results First Submitted: June 7, 2012
Results First Posted: September 13, 2012
Last Update Posted: October 12, 2018