Trial Outcomes & Findings for Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance (NCT NCT00665353)
NCT ID: NCT00665353
Last Updated: 2018-10-12
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
Week 24 of Step 2
Results posted on
2018-10-12
Participant Flow
Subjects were enrolled at 8 ACTG sites. The dates of first and last study enrollments were March 31, 2009 and May 26, 2010, respectively.
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).
Participant milestones
| Measure |
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.
|
|---|---|
|
Study Step 1
STARTED
|
19
|
|
Study Step 1
COMPLETED
|
16
|
|
Study Step 1
NOT COMPLETED
|
3
|
|
Study Step 2
STARTED
|
16
|
|
Study Step 2
COMPLETED
|
2
|
|
Study Step 2
NOT COMPLETED
|
14
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Study Step 1
Adverse Event
|
1
|
|
Study Step 1
Withdrawal by Subject
|
2
|
|
Study Step 2
Lost to Follow-up
|
2
|
|
Study Step 2
Lack of Efficacy
|
12
|
Baseline Characteristics
Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance
Baseline characteristics by cohort
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=19 Participants
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.
|
|---|---|
|
Age, Continuous
|
49 years
STANDARD_DEVIATION 7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White non-Hispanic
|
8 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black non-Hispanic
|
9 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic (regardless of race)
|
2 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=5 Participants
|
|
Age categorical
30 - 39 years
|
1 participants
n=5 Participants
|
|
Age categorical
40 - 49 years
|
9 participants
n=5 Participants
|
|
Age categorical
50 - 59 years
|
8 participants
n=5 Participants
|
|
Age categorical
60 - 69 years
|
1 participants
n=5 Participants
|
|
IV drug history
Never
|
7 participants
n=5 Participants
|
|
IV drug history
Previously
|
12 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
27.7 kg/m^2
STANDARD_DEVIATION 4.1 • n=5 Participants
|
|
HIV-1 RNA
< 50 copies/mL
|
15 participants
n=5 Participants
|
|
HIV-1 RNA
50 - 99 copies/mL
|
2 participants
n=5 Participants
|
|
HIV-1 RNA
100 - 499 copies/mL
|
2 participants
n=5 Participants
|
|
CD4 count
|
567 cells/mm^3
STANDARD_DEVIATION 192 • n=5 Participants
|
|
Nadir CD4 count
<= 50 cells/mm^3
|
4 participants
n=5 Participants
|
|
Nadir CD4 count
51 - 100 cells/mm^3
|
4 participants
n=5 Participants
|
|
Nadir CD4 count
101 - 200 cells/mm^3
|
4 participants
n=5 Participants
|
|
Nadir CD4 count
201 - 500 cells/mm^3
|
6 participants
n=5 Participants
|
|
Nadir CD4 count
> 500 cells/mm^3
|
1 participants
n=5 Participants
|
|
Thyrotropin
|
1.49 mIU/L
STANDARD_DEVIATION 0.67 • n=5 Participants
|
|
Hemoglobin
|
14.4 g/dL
STANDARD_DEVIATION 1.5 • n=5 Participants
|
|
Absolute neutrophil count
|
2501 cells/mm^3
STANDARD_DEVIATION 1031 • n=5 Participants
|
|
Platelets
|
185842 cells/mm^3
STANDARD_DEVIATION 67375 • n=5 Participants
|
|
Direct bilirubin
|
1.0 * ULN
STANDARD_DEVIATION 0.6 • n=5 Participants
|
|
Alanine Aminotransferase (ALT)
|
1.4 * ULN
STANDARD_DEVIATION 1.2 • n=5 Participants
|
|
Aspartate Aminotransferase (AST)
|
1.5 * ULN
STANDARD_DEVIATION 0.9 • n=5 Participants
|
|
Gamma-glutamyl transferase
|
154 U/L
STANDARD_DEVIATION 127 • n=5 Participants
|
|
Fasting glucose
|
100 mg/dL
STANDARD_DEVIATION 12 • n=5 Participants
|
|
Fasting insulin
|
25 mIU/L
STANDARD_DEVIATION 13 • n=5 Participants
|
|
Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)
|
6.3 mg/dL x mIU/L / 405
STANDARD_DEVIATION 3.5 • n=5 Participants
|
|
Prior hepatitis C virus (HCV) non-response type
< 2 log10 drop AND detectable >= 10 and < 22 weeks
|
13 participants
n=5 Participants
|
|
Prior hepatitis C virus (HCV) non-response type
Detectable after >= 22 and < 30 weeks
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24 of Step 2Population: All enrolled subjects.
Outcome measures
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=19 Participants
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.
|
|---|---|
|
The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 24 of Step 2.
|
0.158 proportion of participants
Interval 0.059 to 1.0
|
SECONDARY outcome
Timeframe: Step 1 (Up to 24 to 28 weeks)Population: All enrolled subjects.
Summary of the number of subjects with at least one grade 3 or higher sign/symptom or laboratory abnormality.
Outcome measures
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=19 Participants
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.
|
|---|---|
|
Safety and Tolerability
|
7 participants
|
SECONDARY outcome
Timeframe: Step 2 (Up to 72 weeks)Population: All subject enrolled in Step 2.
Summary of the number of subjects with at least one grade 3 or higher sign/symptom or laboratory abnormality.
Outcome measures
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=16 Participants
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.
|
|---|---|
|
Safety and Tolerability
|
13 participants
|
SECONDARY outcome
Timeframe: Week 72 of Step 2Population: All enrolled subjects.
Outcome measures
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=19 Participants
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.
|
|---|---|
|
The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 72of Step 2.
|
0.053 proportion of participants
Interval 0.001 to 1.0
|
SECONDARY outcome
Timeframe: From Entry to Week 24 of Step 1Population: Subjects with both Entry and Week 24 LFT results.
Outcome measures
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=17 Participants
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.
|
|---|---|
|
Absolute Change From Entry to Week 24 of Step 1 in AST and ALT.
24 week change in ALT (n=17)
|
-0.14 x ULN
Interval -0.47 to 0.02
|
|
Absolute Change From Entry to Week 24 of Step 1 in AST and ALT.
24 week change in AST (n=17)
|
-0.20 x ULN
Interval -0.29 to -0.08
|
SECONDARY outcome
Timeframe: From Entry to Week 24 of Step 1Population: Subjects with both Entry and Week 24 HOMA-IR results.
Outcome measures
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=16 Participants
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.
|
|---|---|
|
Absolute Change From Entry to Week 24 of Step 1 in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)
|
-1.2 mg/dL x uIU/mL / 405
Interval -3.6 to 0.9
|
SECONDARY outcome
Timeframe: From Entry to Week 24 of Step 1Population: Subjects with both Entry and Week 24 fasting lipid results.
Outcome measures
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=16 Participants
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.
|
|---|---|
|
Absolute Change From Entry to Week 24 of Step 1 in Fasting Total Cholesterol and Triglycerides.
24 week change in total cholesterol (n=16)
|
5.5 mg/dL
Interval -2.0 to 20.5
|
|
Absolute Change From Entry to Week 24 of Step 1 in Fasting Total Cholesterol and Triglycerides.
24 week change in triglycerides (n=16)
|
28.5 mg/dL
Interval -15.5 to 73.0
|
Adverse Events
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=19 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Pancreatitis
|
5.3%
1/19
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
5.3%
1/19
|
Other adverse events
| Measure |
PIO (Step 1) Then PIO+PEG-INF+RBV (Step 2)
n=19 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
10.5%
2/19
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.3%
1/19
|
|
Eye disorders
Eye pain
|
5.3%
1/19
|
|
Eye disorders
Glaucoma
|
5.3%
1/19
|
|
Gastrointestinal disorders
Abdominal pain
|
10.5%
2/19
|
|
Gastrointestinal disorders
Cheilitis
|
5.3%
1/19
|
|
Gastrointestinal disorders
Constipation
|
10.5%
2/19
|
|
Gastrointestinal disorders
Diarrhoea
|
10.5%
2/19
|
|
Gastrointestinal disorders
Dry mouth
|
5.3%
1/19
|
|
Gastrointestinal disorders
Epiploic appendagitis
|
5.3%
1/19
|
|
Gastrointestinal disorders
Flatulence
|
5.3%
1/19
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.3%
1/19
|
|
Gastrointestinal disorders
Leukoplakia oral
|
5.3%
1/19
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.3%
1/19
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19
|
|
Gastrointestinal disorders
Oral discomfort
|
5.3%
1/19
|
|
Gastrointestinal disorders
Oral pain
|
5.3%
1/19
|
|
Gastrointestinal disorders
Vomiting
|
10.5%
2/19
|
|
General disorders
Asthenia
|
15.8%
3/19
|
|
General disorders
Chest discomfort
|
5.3%
1/19
|
|
General disorders
Chest pain
|
5.3%
1/19
|
|
General disorders
Chills
|
5.3%
1/19
|
|
General disorders
Fatigue
|
31.6%
6/19
|
|
General disorders
Irritability
|
5.3%
1/19
|
|
General disorders
Malaise
|
5.3%
1/19
|
|
General disorders
Pain
|
5.3%
1/19
|
|
General disorders
Pyrexia
|
10.5%
2/19
|
|
Hepatobiliary disorders
Hepatitis
|
5.3%
1/19
|
|
Infections and infestations
Acute sinusitis
|
5.3%
1/19
|
|
Infections and infestations
Bartholin's abscess
|
5.3%
1/19
|
|
Infections and infestations
Bronchitis
|
5.3%
1/19
|
|
Infections and infestations
Folliculitis
|
5.3%
1/19
|
|
Infections and infestations
Gastroenteritis viral
|
5.3%
1/19
|
|
Infections and infestations
Herpes zoster
|
15.8%
3/19
|
|
Infections and infestations
Oesophageal candidiasis
|
5.3%
1/19
|
|
Infections and infestations
Oral candidiasis
|
5.3%
1/19
|
|
Infections and infestations
Pneumonia bacterial
|
5.3%
1/19
|
|
Infections and infestations
Sinusitis
|
5.3%
1/19
|
|
Infections and infestations
Upper respiratory tract infection
|
15.8%
3/19
|
|
Infections and infestations
Urinary tract infection
|
5.3%
1/19
|
|
Injury, poisoning and procedural complications
Excoriation
|
5.3%
1/19
|
|
Injury, poisoning and procedural complications
Thermal burn
|
5.3%
1/19
|
|
Investigations
Alanine aminotransferase increased
|
68.4%
13/19
|
|
Investigations
Aspartate aminotransferase increased
|
84.2%
16/19
|
|
Investigations
Blood albumin abnormal
|
5.3%
1/19
|
|
Investigations
Blood alkaline phosphatase increased
|
15.8%
3/19
|
|
Investigations
Blood bicarbonate abnormal
|
21.1%
4/19
|
|
Investigations
Blood bilirubin increased
|
15.8%
3/19
|
|
Investigations
Blood creatinine increased
|
5.3%
1/19
|
|
Investigations
Blood glucose abnormal
|
57.9%
11/19
|
|
Investigations
Blood glucose decreased
|
5.3%
1/19
|
|
Investigations
Blood glucose increased
|
15.8%
3/19
|
|
Investigations
Blood phosphorus decreased
|
10.5%
2/19
|
|
Investigations
Blood sodium decreased
|
5.3%
1/19
|
|
Investigations
Haemoglobin decreased
|
36.8%
7/19
|
|
Investigations
Lipase abnormal
|
5.3%
1/19
|
|
Investigations
Lipase increased
|
21.1%
4/19
|
|
Investigations
Neutrophil count decreased
|
63.2%
12/19
|
|
Investigations
Platelet count decreased
|
63.2%
12/19
|
|
Investigations
Weight decreased
|
5.3%
1/19
|
|
Investigations
White blood cell count decreased
|
15.8%
3/19
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.3%
1/19
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
5.3%
1/19
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
36.8%
7/19
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
5.3%
1/19
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
5.3%
1/19
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
21.1%
4/19
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.5%
2/19
|
|
Nervous system disorders
Cervicobrachial syndrome
|
5.3%
1/19
|
|
Nervous system disorders
Cognitive disorder
|
5.3%
1/19
|
|
Nervous system disorders
Disturbance in attention
|
5.3%
1/19
|
|
Nervous system disorders
Dizziness
|
5.3%
1/19
|
|
Nervous system disorders
Hypoaesthesia
|
5.3%
1/19
|
|
Nervous system disorders
Mental impairment
|
5.3%
1/19
|
|
Nervous system disorders
Neuralgia
|
5.3%
1/19
|
|
Nervous system disorders
Paraesthesia
|
5.3%
1/19
|
|
Nervous system disorders
Sinus headache
|
5.3%
1/19
|
|
Psychiatric disorders
Abnormal dreams
|
5.3%
1/19
|
|
Psychiatric disorders
Affective disorder
|
5.3%
1/19
|
|
Psychiatric disorders
Anger
|
5.3%
1/19
|
|
Psychiatric disorders
Anhedonia
|
5.3%
1/19
|
|
Psychiatric disorders
Anxiety
|
15.8%
3/19
|
|
Psychiatric disorders
Depression
|
15.8%
3/19
|
|
Psychiatric disorders
Depressive symptom
|
5.3%
1/19
|
|
Psychiatric disorders
Insomnia
|
21.1%
4/19
|
|
Renal and urinary disorders
Dysuria
|
5.3%
1/19
|
|
Renal and urinary disorders
Renal failure acute
|
5.3%
1/19
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
5.3%
1/19
|
|
Reproductive system and breast disorders
Vulvovaginal pain
|
5.3%
1/19
|
|
Reproductive system and breast disorders
Vulvovaginal swelling
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.5%
2/19
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal oedema
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
10.5%
2/19
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.3%
1/19
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
5.3%
1/19
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
5.3%
1/19
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.3%
1/19
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
5.3%
1/19
|
Additional Information
ACTG ClinicalTrials.gov Coordinator
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place