Ischemic Heart DiseasePhase 4NCT00187889
EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia
A Phase 4 study testing Eplerenone in people with Ischemic Heart Disease, run by University of Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years, women only
- Conditions the study is for
- Ischemic Heart Disease
- What is being tested?
- Eplerenone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Dec 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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 If a patient becomes pregnant or begins breast-feeding during the study, she must be withdrawn immediately.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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Ischemic Heart Disease
- Being tested
- Eplerenone, Placebo or sugar pill
- Keywords
- Microvascular Disease, Women, Ischemic Heart Disease, WISE
- Medical subject headings
- Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.
Placebo or sugar pillDrug
Also called Placebo
Placebo blinded as 25 mg tablet(1 pill) once daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Eplerenone | Active comparator | Eplerenone 25 mg (1 pill)daily for 1 week then uptitrated to 50 mg (2 pills)daily for 15 weeks. Receives: 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. Receives: Drug: Placebo or sugar pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Coronary flow reserve is a ratio of coronary blood flow velocity before and after adenosine. The outcome measure is the difference between the coronary flow reserve at 16 weeks adjusted for coronary flow reserve at baseline.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startAug 2004
- Primary completionFeb 2009
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemic Heart DiseaseStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Pfizer
- Responsible party
- Sponsor
- Investigators
- Carl J Pepine, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00187889
- Sponsor's protocol ID
- EWISE
- Other IDs
- R01 H267173-01
- Status last verified
- Oct 2011
- First submitted
- 10 Sep 2005
- Last updated
- 14 Oct 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 24890531
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00187889
- Acronym / sponsor ID
- EWISE
- Conditions
- Ischemic Heart Disease
- Keywords
- Microvascular Disease, Women, Ischemic Heart Disease, WISE
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Pfizer
- Study start
- Aug 2004
- Primary completion
- Feb 2009 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 14 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eplerenone | Active comparator | Drug: EplerenoneEplerenone 25 mg (1 pill)daily for 1 week then uptitrated to 50 mg (2 pills)daily for 15 weeks. |
| Placebo or sugar pill | Placebo comparator | Drug: Placebo or sugar pillPlacebo blinded as 25 mg tablet once daily for 1 week then uptitrated to 2 pills daily for 15 weeks. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EplerenoneEplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks. | Drug | Eplerenone |
| Placebo or sugar pillAlso: PlaceboPlacebo blinded as 25 mg tablet(1 pill) once daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks. | Drug | Placebo or sugar pill |
Primary outcome
Epicardial Coronary Artery Endothelial Function (Adjusted) at Week 16 Comparing the Eplerenone Group to the Placebo Group
Time frame: 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.
1 secondary outcome
Microvascular Coronary Flow Reserve(Adjusted) at Week 16 Adjusted for Baseline Coronary Flow Reserve Comparing the Eplerenone Group to the Placebo Group
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24890531Bavry 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carl J Pepine, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Eplerenone in people with Ischemic Heart Disease, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epicardial Coronary Artery Endothelial Function (Adjusted) at Week 16 Comparing the Eplerenone Group to the Placebo Group (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00187889, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2013.