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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Epicardial Coronary Artery Endothelial Function (Adjusted) at Week 16 Comparing the Eplerenone Group to the Placebo Group
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
- •Use of potassium supplements or potassium sparing diuretics
研究组 & 干预措施
Eplerenone
Eplerenone 25 mg (1 pill)daily for 1 week then uptitrated to 50 mg (2 pills)daily for 15 weeks.
干预措施: Eplerenone (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.
干预措施: Placebo or sugar pill (Drug)
结局指标
主要结局
Epicardial Coronary Artery Endothelial Function (Adjusted) at Week 16 Comparing the Eplerenone Group to the Placebo Group
时间窗: 16 weeks
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.
次要结局
- Microvascular Coronary Flow Reserve(Adjusted) at Week 16 Adjusted for Baseline Coronary Flow Reserve Comparing the Eplerenone Group to the Placebo Group(16 weeks)