Clinical trial NCT00187889
Conditions: Ischemic Heart Disease
Keywords: Microvascular Disease Women Ischemic Heart Disease WISE
Sponsor: University of Florida
Start date: 2004-08-01; Completion date: 2011-12-01
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Some women have chest pain even without having a blockage in one of the major blood vessels that supplies blood to the heart. In many of these women the microscopic (small) blood vessels in the heart do not function normally. This study seeks to determine if treatment with eplerenone, a commercially available diuretic, can improve the function of these microscopic blood vessels and, possibly, improve the chest pain.

Detailed description:
INDICATION: Coronary Vascular Dysfunction (Endothelial Dysfunction and/or Microvascular angina).

OBJECTIVES: To investigate effects of aldosterone blockade (eplerenone) on coronary vascular function.

PATIENT POPULATION: Women who meet the National Heart, Lung and Blood Institute-sponsored WISE (Women Ischemia Syndrome Evaluation) study criteria of chest discomfort, coronary vascular dysfunction and undergoing evaluation for myocardial ischemia in the absence of significant coronary artery stenosis.

STUDY DESIGN: A prospective, randomized, double blind placebo-controlled, comparative trial of eplerenone, given in the presence of a renin-angiotensin blocker (ACE-I or ARB in the case of ACE-I intolerance).

TREATMENT: Eplerenone 25mg titrated to 50mg as tolerated per day versus placebo for four months

PRIMARY EFFICACY PARAMETER(S): Epicardial coronary artery endothelial function at Week 16 (adjusted for baseline treatment group and site by treatment interaction variables) comparing the eplerenone group to the placebo group.

SECONDARY EFFICACY PARAMETERS: Microvascular coronary endothelial function at Week 16 (adjusted for baseline treatment group and site by treatment interaction variables) comparing the eplerenone group to the placebo group.

OTHER EFFICACY PARAMETERS:

* Coronary flow reserve
* Chest discomfort as measured by the Seattle Angina Questionnaire
* DASI

SAFETY PARAMETERS: Blood pressure, pulse rate and frequency and occurrence of adverse events. The latter will include serum K and Creatinine.

STATISTICAL RATIONALE AND ANALYSIS: A statistical rationale for the number of patients in the study has been provided. Interim analyses are planned after 10 patients have completed treatment in each group.

ANTICIPATED TOTAL NUMBER OF PATIENTS: 50 (25 per treatment group).

ANTICIPATED NUMBER OF PATIENTS AT EACH SITE: Approximately 13.

PARTICIPATING SITES: University of Florida (Carl Pepine, MD), Emory University (Arshed Quyyumi, MD), Rhode Island Hospital (Barry Sharaf, MD), and Mayo Clinic (Amir Lerman, MD). There is an existing relationship between the first 3 sites and the Mayo Clinic site is familiar with all necessary protocol procedures and is anxious to participate. The University of Florida will serve as the main contracting site.

Arms: arm 1: Eplerenone 25 mg (1 pill)daily for 1 week then uptitrated to 50 mg (2 pills)daily for 15 weeks. arm 2: Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.
Interventions: intervention 1: Eplerenone intervention 2: Placebo or sugar pill
Intervention descriptions: intervention 1: Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks. intervention 2: Placebo blinded as 25 mg tablet(1 pill) once daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.

Protocol documents: