Trial Outcomes & Findings for Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation (NCT NCT01186250)

Results Overview

Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Baseline and 1 year

Results posted on

2016-08-18

Participant Flow

Participant milestones

Participant milestones
Measure	Pioglitazone Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo Placebo Placebo: placebo taken daily for one year
Overall Study STARTED	9	9
Overall Study COMPLETED	8	9
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pioglitazone n=9 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=9 Participants Placebo Placebo: placebo taken daily for one year	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	50.8 years n=5 Participants	49.2 years n=7 Participants	50.0 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 1 year

Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year.

Outcome measures

Outcome measures
Measure	Pioglitazone n=9 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=9 Participants Placebo Placebo: placebo taken daily for one year
Insulin Levels Area Under Curve(AUC)	-47.7 h*pmol/L Interval -171.3 to 75.9	10.7 h*pmol/L Interval -76.8 to 98.2

SECONDARY outcome

Timeframe: baseline and 1 year

Population: The number of participants enrolled were not all included in the intimal volume analysis because the Angiographic diagnostic evaluation needed for intimal volume measurement was clinically inappropriate for 3 in the pioglitazone arm and 5 in the Placebo arm at 12 months post transplant.

Intimal volume is defined as external elastic membrane volume minus lumen (luminal) volume measured at the heart Catheterization and intravascular Ultrasound( IVUS)

Outcome measures

Outcome measures
Measure	Pioglitazone n=6 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=4 Participants Placebo Placebo: placebo taken daily for one year
Change in Intimal Volume	12.2 mm^3 Standard Deviation 39.9	-26.8 mm^3 Standard Deviation 46.7

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: One participant in each group did not complete the OGTT.

Oral Glucose Tolerance Test : blood was drawn for fasting plasma glucose and insulin levels, followed by ingestion of a solution containing 75grams of glucose. Repeat blood samples were collected for glucose and insulin levels at 30, 90, and 120 minutes after glucose ingestion. All glucose measurements were performed by the Clinical Translational Research Unit (CTRU) Stanford University.

Outcome measures

Outcome measures
Measure	Pioglitazone n=8 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=8 Participants Placebo Placebo: placebo taken daily for one year
Change in Levels of Fasting Glucose at Baseline and 1 Year	2.1 mg/dL Standard Deviation 19	11 mg/dL Standard Deviation 33

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: One drop out

Triglyceride ratio to High Density Lipoprotien

Outcome measures

Outcome measures
Measure	Pioglitazone n=8 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=8 Participants Placebo Placebo: placebo taken daily for one year
Change From Baseline in TG/HDL Ratio at One Year	-0.03 ratio Standard Deviation 6	-1.2 ratio Standard Deviation 3.3

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: number participants analyzed contained drops out due to clinical reasons

The change in maximal intimal thickness (MIT) from baseline to one year was recorded for several matched sites in the same coronary artery, the cross sections, predominantly in the left anterior descending coronary artery, from baseline to one-year follow-up, were studied. The IVUS cross sections were matched by using identifiable landmarks in the images, such as bifurcations or arterial calcification, or external landmarks, such as coronary veins or pericardium. In addition, the one-year IVUS studies were obtained with an angiographic roadmap of where the initial IVUS study was performed along the length of the vessel. The IVUS system auto pullback was performed at .5 mm/s from the mid-distal portion of the study vessel, where an easily identifiable landmark was visible (i.e., branchpoint). The following items were measured for each patient: maximal intimal thickness (MIT), intimal area (IA), and vessel area.

Outcome measures

Outcome measures
Measure	Pioglitazone n=6 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=4 Participants Placebo Placebo: placebo taken daily for one year
Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS)	-0.01 mm Standard Deviation 0.3	-0.02 mm Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: One participant in one arm did not have Baseline or one year data.

Competitive ELISA assay in Stanford laboratory.

Outcome measures

Outcome measures
Measure	Pioglitazone n=8 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=8 Participants Placebo Placebo: placebo taken daily for one year
Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year.	-0.05 umol/L Standard Deviation 0.1	-0.02 umol/L Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: participant drop put

measure of low levels of C-reactive protein to identify low but persistent levels of inflammation

Outcome measures

Outcome measures
Measure	Pioglitazone n=7 Participants Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months	Placebo n=7 Participants Placebo Placebo: placebo taken daily for one year
Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year	-3 mg/L Standard Deviation 3	2 mg/L Standard Deviation 4

Adverse Events

Pioglitazone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Kiran K. Khush, MD

Stanford University

Phone: 650-721-3241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place