Trial Outcomes & Findings for Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS) (NCT NCT00063622)
NCT ID: NCT00063622
Last Updated: 2018-04-06
Results Overview
Total nonalcoholic fatty liver disease (NAFLD) activity was assessed on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (assessed on a scale of 0 to 3), lobular inflammation (assessed on a scale of 0 to 3), and hepatocellular ballooning (assessed on a scale of 0 to 2). The primary outcome was an improvement in histological findings from baseline to 96 weeks, which required an improvement by 1 or more points in the hepatocellular ballooning score; no increase in the fibrosis score; and either a decrease in the activity score for nonalcoholic fatty liver disease to a score of 3 or less or a decrease in the activity score of at least 2 points, with at least a 1-point decrease in either the lobular inflammation or steatosis score.
COMPLETED
PHASE3
247 participants
baseline and 96 weeks
2018-04-06
Participant Flow
PIVENS enrollment started in January 2005 and ended in January 2007.
A total of 339 patients were registered and screened for PIVENS trial, 92 of whom (27%) were found ineligible. The failure to meet histological entry criteria and fasting blood glucose \>125 mg/dL were the most frequent reasons for ineligibility.
Participant milestones
| Measure |
Pioglitazone
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
Vitamin E at a dose of 800 IU daily
|
Placebo
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Overall Study
STARTED
|
80
|
84
|
83
|
|
Overall Study
COMPLETED
|
70
|
80
|
72
|
|
Overall Study
NOT COMPLETED
|
10
|
4
|
11
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS)
Baseline characteristics by cohort
| Measure |
Pioglitazone
n=80 Participants
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=84 Participants
Vitamin E at a dose of 800 IU daily
|
Placebo
n=83 Participants
Placebo Pioglitazone and Placebo Vitamin E
|
Total
n=247 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47.0 years
STANDARD_DEVIATION 12.6 • n=99 Participants
|
46.6 years
STANDARD_DEVIATION 12.1 • n=107 Participants
|
45.4 years
STANDARD_DEVIATION 11.2 • n=206 Participants
|
46.3 years
STANDARD_DEVIATION 11.9 • n=7 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=99 Participants
|
52 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
147 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
100 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
80 participants
n=99 Participants
|
84 participants
n=107 Participants
|
83 participants
n=206 Participants
|
247 participants
n=7 Participants
|
|
Total nonalcoholic fatty liver disease (NAFLD) activity score
|
5.0 scores on a scale
STANDARD_DEVIATION 1.4 • n=99 Participants
|
5.1 scores on a scale
STANDARD_DEVIATION 1.4 • n=107 Participants
|
4.8 scores on a scale
STANDARD_DEVIATION 1.4 • n=206 Participants
|
4.9 scores on a scale
STANDARD_DEVIATION 1.4 • n=7 Participants
|
PRIMARY outcome
Timeframe: baseline and 96 weeksPopulation: All randomized participants were included in the analysis of the primary outcome.
Total nonalcoholic fatty liver disease (NAFLD) activity was assessed on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (assessed on a scale of 0 to 3), lobular inflammation (assessed on a scale of 0 to 3), and hepatocellular ballooning (assessed on a scale of 0 to 2). The primary outcome was an improvement in histological findings from baseline to 96 weeks, which required an improvement by 1 or more points in the hepatocellular ballooning score; no increase in the fibrosis score; and either a decrease in the activity score for nonalcoholic fatty liver disease to a score of 3 or less or a decrease in the activity score of at least 2 points, with at least a 1-point decrease in either the lobular inflammation or steatosis score.
Outcome measures
| Measure |
Pioglitazone
n=80 Participants
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=84 Participants
Vitamin E at a dose of 800 IU daily
|
Placebo
n=83 Participants
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Number of Participants With Improvement in Non-alcoholic Fatty Liver Disease (NAFLD) Activity Defined by Change in Standardized Scoring of Liver Biopsies at Baseline and After 96 Weeks of Treatment.
|
27 participants
|
36 participants
|
16 participants
|
SECONDARY outcome
Timeframe: baseline and 96 weeksPopulation: Number of subjects with biopsy specimens at baseline and 96 weeks
Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis. This secondary outcome measure is the number of participants that experienced a decrease in steatosis score, which indicates improvement in steatosis.
Outcome measures
| Measure |
Pioglitazone
n=70 Participants
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=80 Participants
Vitamin E at a dose of 800 IU daily
|
Placebo
n=72 Participants
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Number of Participants With Improvement in Steatosis
|
48 participants
|
43 participants
|
22 participants
|
SECONDARY outcome
Timeframe: baseline and 96 weeksPopulation: Number of subjects with biopsy specimens at baseline and 96 weeks
Lobular inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe lobular inflammation. This secondary outcome measure is the number of participants that experienced a decrease in lobular inflammation score, which indicates improvement in lobular inflammation.
Outcome measures
| Measure |
Pioglitazone
n=70 Participants
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=80 Participants
Vitamin E at a dose of 800 IU daily
|
Placebo
n=72 Participants
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Number of Participants With Improvement in Lobular Inflammation
|
41 participants
|
43 participants
|
25 participants
|
SECONDARY outcome
Timeframe: baseline and 96 weeksPopulation: Number of subjects with biopsy specimens at baseline and 96 weeks
Hepatocellular ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe hepatocellular ballooning. This secondary outcome measure is the number of participants that experienced a decrease in hepatocellular ballooning score, which indicates improvement in hepatocellular ballooning.
Outcome measures
| Measure |
Pioglitazone
n=70 Participants
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=80 Participants
Vitamin E at a dose of 800 IU daily
|
Placebo
n=72 Participants
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Number of Participants With Improvement in Hepatocellular Ballooning
|
31 participants
|
40 participants
|
21 participants
|
SECONDARY outcome
Timeframe: baseline and 96 weeksPopulation: Number of subjects with biopsy specimens at baseline and 96 weeks
Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis. This secondary outcome measure is the number of participants that experienced a decrease in fibrosis score, which indicates improvement in fibrosis.
Outcome measures
| Measure |
Pioglitazone
n=70 Participants
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=80 Participants
Vitamin E at a dose of 800 IU daily
|
Placebo
n=72 Participants
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Number of Participants With Improvement in Fibrosis
|
31 participants
|
33 participants
|
22 participants
|
SECONDARY outcome
Timeframe: baseline and 96 weeksPopulation: Number of subjects with biopsy specimens at baseline and 96 weeks
The criteria for nonalcoholic steatohepatitis was definite or possible steatohepatitis (assessed by a pathologist) with an activity score of 5 or more, or definite steatohepatitis (confirmed by two pathologists) with an activity score of 4. This secondary outcome measure is the number of participants who met this definition at baseline and did not meet this definition after 96 weeks of treatment and thus had a resolution of steatohepatitis.
Outcome measures
| Measure |
Pioglitazone
n=70 Participants
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=80 Participants
Vitamin E at a dose of 800 IU daily
|
Placebo
n=72 Participants
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Number of Participants With Resolution of Definite Nonalcoholic Steatohepatitis
|
33 participants
|
29 participants
|
15 participants
|
Adverse Events
Pioglitazone
Vitamin E
Placebo
Serious adverse events
| Measure |
Pioglitazone
n=80 participants at risk
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=84 participants at risk
Vitamin E at a dose of 800 IU daily
|
Placebo
n=83 participants at risk
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
General disorders
Severe adverse event
|
2.5%
2/80
|
8.3%
7/84
|
12.0%
10/83
|
Other adverse events
| Measure |
Pioglitazone
n=80 participants at risk
Pioglitazone at a dose of 30 mg daily
|
Vitamin E
n=84 participants at risk
Vitamin E at a dose of 800 IU daily
|
Placebo
n=83 participants at risk
Placebo Pioglitazone and Placebo Vitamin E
|
|---|---|---|---|
|
Cardiac disorders
Cardiovascular Event
|
12.5%
10/80
|
14.3%
12/84
|
14.5%
12/83
|
|
Musculoskeletal and connective tissue disorders
Bone fracture
|
3.8%
3/80
|
3.6%
3/84
|
6.0%
5/83
|
|
Endocrine disorders
Diabetes
|
0.00%
0/80
|
4.8%
4/84
|
0.00%
0/83
|
|
Hepatobiliary disorders
Cirrhosis
|
0.00%
0/80
|
1.2%
1/84
|
0.00%
0/83
|
|
General disorders
Other mild and moderate adverse event
|
35.0%
28/80
|
31.0%
26/84
|
27.7%
23/83
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place