Trial Outcomes & Findings for EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia (NCT NCT00187889)

Results Overview

The primary measure was the relative change in coronary diameter to acetylcholinem (ACH) at 16 weeks adjusted for baseline reactivity to acetylcholine. Change in coronary artery diameter after ACH was measured in mm at baseline and 16 weeks. Percent change at 16 weeks - percent change at baseline was the outcome.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

70 participants

Primary outcome timeframe

16 weeks

Results posted on

2013-10-14

Participant Flow

The participants was recruited into the study by using flyers, and asked about interest in the medical clinics.

A total of 70 participants were screened for the study. Out of the 70 participants a total of 18 screened failed, 1 patient was withdrawn due to developing a spasm during the provocative testing screening which was believed to represent thrombosis and was not randomized to the study.

Participant milestones

Participant milestones
Measure	Eplerenone Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.	Placebo or Sugar Pill Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.
Overall Study STARTED	25	26
Overall Study COMPLETED	19	22
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Eplerenone Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.	Placebo or Sugar Pill Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.
Overall Study Withdrawal by Subject	6	4

Baseline Characteristics

EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Epleranone n=25 Participants Epleranone 25 mg daily for 1 week then uptitrated to 50 mg daily for 15 weeks.	Placebo or Sugar Pill n=26 Participants Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.	Total n=51 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	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Age Continuous	53 years STANDARD_DEVIATION 9 • n=5 Participants	54 years STANDARD_DEVIATION 11 • n=7 Participants	53 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	26 participants n=7 Participants	51 participants n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: power analysis: Study planned to detect a 12% difference in change from baseline to 16 weeks between treatment groups (SD=14%), in the primary outcome leading to a planned sample size of 22 per group (44 total) for 80% power, P=0.05 2-sided. Study allowed for 6 dropouts, leading to a final N=50 planned (25 per group). Per protocol analysis used.

The primary measure was the relative change in coronary diameter to acetylcholinem (ACH) at 16 weeks adjusted for baseline reactivity to acetylcholine. Change in coronary artery diameter after ACH was measured in mm at baseline and 16 weeks. Percent change at 16 weeks - percent change at baseline was the outcome.

Outcome measures

Outcome measures
Measure	EPLERINONE n=19 Participants Active drug	PLACEBO n=22 Participants Inert Placebo
Epicardial Coronary Artery Endothelial Function (Adjusted) at Week 16 Comparing the Eplerenone Group to the Placebo Group	-1.2 % change wk16-%change wk0- unitless Standard Deviation 15.4	-10.7 % change wk16-%change wk0- unitless Standard Deviation 25.6

SECONDARY outcome

Timeframe: 16 weeks

Population: See Primary Outcome. The studied was only powered for the primary outcome. All completers are included per protocol analysis.

Coronary flow reserve is a ratio of coronary blood flow velocity before and after adenosine. The outcome measure is the difference between the coronary flow reserve at 16 weeks adjusted for coronary flow reserve at baseline.

Outcome measures

Outcome measures
Measure	EPLERINONE n=13 Participants Active drug	PLACEBO n=18 Participants Inert Placebo
Microvascular Coronary Flow Reserve(Adjusted) at Week 16 Adjusted for Baseline Coronary Flow Reserve Comparing the Eplerenone Group to the Placebo Group	-0.4 difference of ratios (unitless) Standard Deviation 0.9	-0.4 difference of ratios (unitless) Standard Deviation 1.2

Adverse Events

Epleranone

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo or Sugar Pill

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Epleranone n=24 participants at risk Epleranone 25 mg daily for 1 week then uptitrated to 50 mg daily for 15 weeks.	Placebo or Sugar Pill n=26 participants at risk Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.
Vascular disorders Deep venous thrombosis	4.2% 1/24 • Number of events 1	0.00% 0/26

Other adverse events

Other adverse events
Measure	Epleranone n=24 participants at risk Epleranone 25 mg daily for 1 week then uptitrated to 50 mg daily for 15 weeks.	Placebo or Sugar Pill n=26 participants at risk Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.
Cardiac disorders chest pain	12.5% 3/24 • Number of events 3	11.5% 3/26 • Number of events 3

Additional Information

Dr. Carl J. Pepine

University of Florida

Phone: 352-273-9082

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place