EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia
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.
Ischemic Heart Disease
Drug: placebo or sugar pill
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Double-Blind, Multicenter, Placebo Controlled Study of Aldosterone Blockade (Eplerenone) in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia in the Absence of Significant Epicardial Coronary Artery Disease|
- Epicardial coronary artery endothelial function (adjusted) at Week 16 comparing the eplerenone group to the placebo group [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Microvascular coronary endothelial function (adjusted) at Week 16 comparing the eplerenone group to the placebo group [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||August 2004|
|Study Completion Date:||December 2011|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
|Active Comparator: epleranone||
Epleranone 25 mg daily for 1 week then uptitrated to 50 mg daily for 15 weeks
|Placebo Comparator: Placebo or sugar pill||
Drug: placebo or sugar pill
Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks
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
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.
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32610|
|Principal Investigator:||Carl J Pepine, MD||University of Florida|