EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia
Condition: Ischemic Heart Disease
MeSH terms: Heart Diseases; Myocardial Ischemia; Coronary Artery Disease; Ischemia; Chest Pain
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Eplerenone; Placebo or sugar pill
Intervention type(s): Drug; Drug
Intervention description(s): Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.; Placebo blinded as 25 mg tablet(1 pill) once daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.
Other intervention name(s): Placebo
Intervention MeSH terms: Eplerenone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Microvascular Disease; Women; Ischemic Heart Disease; WISE