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

NCT00187889 | Completed Phase 4 Results DMC

• 2 other identifiers: EWISER01 H267173-01
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Heart Disease

Keywords

Microvascular Disease; Women; Ischemic Heart Disease; WISE

Outcome Measures

Primary Outcomes (1)

• Epicardial Coronary Artery Endothelial Function (Adjusted) at Week 16 Comparing the Eplerenone Group to the Placebo Group

  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.

  16 weeks

Secondary Outcomes (1)

• Microvascular Coronary Flow Reserve(Adjusted) at Week 16 Adjusted for Baseline Coronary Flow Reserve Comparing the Eplerenone Group to the Placebo Group

  16 weeks

Study Arms (2)

Eplerenone

ACTIVE COMPARATOR

Eplerenone 25 mg (1 pill)daily for 1 week then uptitrated to 50 mg (2 pills)daily for 15 weeks.

Drug: Eplerenone

Placebo or sugar pill

PLACEBO COMPARATOR

Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.

Drug: Placebo or sugar pill

Interventions

Eplerenone DRUG

Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.

Eplerenone

Placebo or sugar pill DRUG

Placebo blinded as 25 mg tablet(1 pill) once daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.

Also known as: Placebo

Placebo or sugar pill

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-pregnant women with chest discomfort who are 21 to 75 years of age and from diverse racial/ethnic groups.
• Suspected ischemic heart disease (IHD) but no severe coronary stenosis (\> 50% diameter reduction) on coronary angiography used to qualify for WISE.
• Endothelial dysfunction, defined as failure to dilate to intracoronary acetylcholine (\< 5% increase in mean lumen diameter).
• If possible, patients should be taking stable, maximally tolerated dose of either an angiotensin-converting enzyme inhibitor \[ACEI\] (or an angiotensin II receptor blocker \[ARB\] if ACEI intolerant)

You may not qualify if:

• Women who are breast-feeding or who are pregnant. Women of childbearing potential may be enrolled but must agree not to become pregnant during the course of the study and must practice a method of birth control considered reliable by the investigator. If established on hormonal contraceptives for more than 3 months, patients will be allowed to participate provided that this therapy remains constant throughout the study. If a patient becomes pregnant or begins breast-feeding during the study, she must be withdrawn immediately.
• Acute ischemic syndrome defined as acute myocardial infarction \[MI\] (by enzyme or electrocardiogram \[ECG\] criteria) or unstable angina within 1 month of entry.
• Uncontrolled moderate hypertension: sitting blood pressure \> 160/95mmHg with measurements recorded on at least 2 occasions (for blood pressure control patients must first be stabilized, preferably with a diuretic, and remain on that dosing regimen throughout participation in the study).
• Severe heart failure defined as New York Heart Association (NYHA) Class III or IV on treatment.
• Coronary revascularization by either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) or stent placement.
• Conditions likely to influence outcomes independent of IHD: severe lung, renal (creatinine \>1.8 or creatinine clearance \[CrCl\] ≤ 50ml/min) or hepatic disease; surgically uncorrected significant congenital or valvular heart disease; and other diseases likely to be fatal or require frequent hospitalizations within the next six months.
• Adherence or retention reasons: recent alcoholism or drug abuse; psychiatric illness including severe depression; dementia; active participation in any other research trial other than WISE; or unwilling to complete follow-up evaluations including repeat testing.
• Hypersensitivity to any medications to be used in the study
• Documented obstructive hypertrophic cardiomyopathy.
• Aortic stenosis (valve area \< 1.5cm).
• Left ventricular (LV) dysfunction (ejection fraction \<= 35%).
• History of significant cocaine or amphetamine abuse.
• Serum potassium \> 5.0meq/l at baseline
• Taking potent CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir)
• Intolerance to ACEI and ARB medications

Sponsors & Collaborators

• University of Florida: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Pfizer: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (1)

• Bavry AA, Handberg EM, Huo T, Lerman A, Quyyumi AA, Shufelt C, Sharaf B, Merz CN, Cooper-DeHoff RM, Sopko G, Pepine CJ. Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: an ancillary study of the national heart, lung, and blood institute-sponsored women's ischemia syndrome evaluation. Am Heart J. 2014 Jun;167(6):826-32. doi: 10.1016/j.ahj.2014.01.017. Epub 2014 Mar 1.

  PMID: 24890531 DERIVED

MeSH Terms

Conditions

Myocardial Ischemia

Interventions

Eplerenone; Sugars

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Dr. Carl J. Pepine
• Organization: University of Florida

carl.pepine@medicine.ufl.edu

352-273-9082

Study Officials

• Carl J Pepine, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2004
• Primary Completion: February 1, 2009
• Study Completion: December 1, 2011
• Last Updated: October 14, 2013
• Results First Posted: October 14, 2013

Record last verified: 2011-10

Locations

US (1)