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

NCT00187889

Last updated date
Study Location
University of Florida
Gainesville, Florida, 32610, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Ischemic Heart Disease
Sex
Female
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
21-75 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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)

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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must be withdrawn immediately.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

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Ischemic Heart DiseaseEWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia
NCT00187889
  1. Gainesville, Florida
Female
21 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ischemic Heart Disease
Intervention  ICMJE
  • Drug: Eplerenone
    Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.
  • Drug: Placebo or sugar pill
    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 Name: Placebo
Study Arms  ICMJE
  • Active Comparator: Eplerenone
    Eplerenone 25 mg (1 pill)daily for 1 week then uptitrated to 50 mg (2 pills)daily for 15 weeks.
    Intervention: Drug: Eplerenone
  • Placebo Comparator: Placebo or sugar pill
    Placebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks.
    Intervention: Drug: Placebo or sugar pill
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 7, 2013)
70
Original Enrollment  ICMJE
 (submitted: September 10, 2005)
50
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study:Female
Ages  ICMJE 21 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00187889
Other Study ID Numbers  ICMJE EWISE
R01 H267173-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Pfizer
Investigators  ICMJE
Principal Investigator:Carl J Pepine, MDUniversity of Florida
PRS Account University of Florida
Verification Date October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP