Trial Outcomes & Findings for Angiotensin Converting Enzyme (ACE) Inhibition and Cardiac Allograft Vasculopathy (NCT NCT01078363)

Results Overview

also called transplant coronary artery disease or cardiac transplant vasculopathy defined as coronary artery stenosis(narrowing) ranging from 30 to 70 percent by coronary angiography. Measured in this study as change in IVUS-assessed Plaque Volume from baseline to one year.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

96 participants

Primary outcome timeframe

Baseline and 1 Year

Results posted on

2017-01-26

Participant Flow

Participant milestones

Participant milestones
Measure	Ramipril ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
Overall Study STARTED	47	49
Overall Study COMPLETED	47	49
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Angiotensin Converting Enzyme (ACE) Inhibition and Cardiac Allograft Vasculopathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramipril n=47 Participants ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=49 Participants Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Total n=96 Participants Total of all reporting groups
Age, Continuous	55 years STANDARD_DEVIATION 15 • n=5 Participants	52 years STANDARD_DEVIATION 17 • n=7 Participants	53 years STANDARD_DEVIATION 16 • n=5 Participants
Gender Female	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Gender Male	36 Participants n=5 Participants	32 Participants n=7 Participants	68 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 1 Year

also called transplant coronary artery disease or cardiac transplant vasculopathy defined as coronary artery stenosis(narrowing) ranging from 30 to 70 percent by coronary angiography. Measured in this study as change in IVUS-assessed Plaque Volume from baseline to one year.

Outcome measures

Outcome measures
Measure	Ramipril n=47 Participants ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=49 Participants Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
Cardiac Allograft Vasculopathy(CAV) Defined as Change in IVUS-assessed Plaque Volume From Baseline to One Year	3.39 mm3/mm Standard Deviation 1.65	3.65 mm3/mm Standard Deviation 1.89

SECONDARY outcome

Timeframe: At Baseline and 1 Year

Population: Only a subset of participants (those adult patients enrolled at Stanford University) underwent the acetylcholine measurements.

The percent change in diameter of the left anterior descending artery was measured by quantitative angiography after acetylcholine and compared to baseline angiography. The percentage of participants who had ≥20% coronary artery diameter reduction after acetylcholine at one year is presented.

Outcome measures

Outcome measures
Measure	Ramipril n=25 Participants ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=22 Participants Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
Percentage of Participants With ≥20% Coronary Artery Diameter Reduction After Acetylcholine	9.4 percentage of participants	4.8 percentage of participants

SECONDARY outcome

Timeframe: 1 year post Transplant

Population: Blood samples were not acquired in all participants which accounts for the discrepancy in number of participants analyzed.

asymmetric dimethylarginine (ADMA), is an inhibitor of endothelial nitric oxide synthase which is a primary regulator of endothelial function.

Outcome measures

Outcome measures
Measure	Ramipril n=41 Participants ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=40 Participants Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
ADMA Level at One Year Post Transplant	.54 micromole Standard Deviation .14	.55 micromole Standard Deviation .16

SECONDARY outcome

Timeframe: at one year

Population: Not all blood samples obtained were adequate for EPC determination which explains the discrepancy in number of participants analyzed.

The determination of the percentage of EPC in peripheral blood involved surface staining peripheral blood mononuclear cells (PBMCs) with appropriate fluorescently-labeled antibodies to delineate EPCs from other blood cells, followed by analysis by conventional flow cytometry.

Outcome measures

Outcome measures
Measure	Ramipril n=40 Participants ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=40 Participants Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
The Percentage of Endothelial Progenitor Cells ( EPC) in Peripheral Blood in Patients One Year After Transplant	.104 percentage of EPC Standard Deviation .068	.098 percentage of EPC Standard Deviation .133

SECONDARY outcome

Timeframe: at one year post Transplant

Population: Only a subset of participants (adult patients enrolled at Stanford University) underwent fractional flow reserve assessment.

FFR is a technique used in coronary catheterization to measure pressure differences across a coronary artery stenosis (narrowing, usually due to atherosclerosis) to determine the likelihood that the stenosis impedes oxygen delivery to the heart muscle (myocardial ischemia). It is defined as the ratio of the distal coronary pressure to the proximal coronary pressure.

Outcome measures

Outcome measures
Measure	Ramipril n=26 Participants ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=23 Participants Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
Fractional Flow Reserve (FFR) at One Year Post Transplant	.88 Ratio Standard Deviation .04	.90 Ratio Standard Deviation .04

SECONDARY outcome

Timeframe: one year

Population: Only a subset of participants (adult patients enrolled at Stanford University) underwent index of microcirculatory resistance assessment.

The index of microcirculatory resistance (IMR) is a pressure-temperature sensor guidewire-based measurement, performed during cardiac catheterization, of the minimum microcirculatory resistance in a specific coronary artery. The IMR provides a quantitative measure of coronary microvasculature status.

Outcome measures

Outcome measures
Measure	Ramipril n=26 Participants ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=22 Participants Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
Index of Microcirculatory Resistance at One Year Post Heart Transplant	14.4 mmHg x seconds Standard Deviation 6.3	21.5 mmHg x seconds Standard Deviation 20

Adverse Events

Ramipril

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ramipril n=47 participants at risk ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.	Placebo n=49 participants at risk Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year. ramipril or placebo: Use of a ACE ( angiotension converting enzyme) inhibitors versus placebo post heart Transplant for Blood pressure control.
Cardiac disorders Death	4.3% 2/47	4.1% 2/49

Other adverse events

Adverse event data not reported

Additional Information

William F. Fearon, M.D.

Stanford University

Phone: 650 725-2621

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place