Official Title: “A Double-Blind, Multicenter, Placebo Controlled Study of Quinapril in Women With Chest Pain, Coronary Flow Reserve Limitations and Evidence of Myocardial Ischemia in the Absence of Significant Epicardial Coronary Artery Disease.”

INDICATION Microvascular angina. OBJECTIVES To demonstrate the effect of Quinapril in improving coronary microvascular 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 flow reserve limitations and evidence for myocardial ischemia in the absence of significant coronary artery stenosis.

STUDY DESIGN A prospective, randomized, placebo-controlled, comparative trial. TREATMENT Quinapril 80 mg/d versus placebo for four months. PRIMARY EFFICACY PARAMETER(S) Absolute value in coronary flow reserve at Week 16.

SECONDARY EFFICACY PARAMETERS Measurements at Week 16 change in: - Percent flow mediated brachial artery dilation. - Myocardial ischemia as measured by P31 MR spectroscopy (PCr/ATP and Pi/PCr ratios; pH). - Total exercise duration as measured by Modified ACIP ETT. - Chest discomfort as measured by the Seattle Angina Questionnaire. SAFETY PARAMETERS Hematology, blood chemistries, blood pressure and pulse, and frequency and occurrence of adverse events.

STATISTICAL RATIONALE AND ANALYSIS A statistical rationale for the number of patients in the study has been provided. Interim analyses are planned after 15 patients have been enrolled in each group.

ANTICIPATED TOTAL NUMBER OF PATIENTS 78 (39 per group). ANTICIPATED NUMBER OF PATIENTS AT EACH SITE Approximately 26

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

A prospective, randomized, placebo-controlled, comparative trial evaluating the effects of ACE inhibition on microvascular function in women with coronary flow reserve limitations, and chest discomfort. Women who are enrolled in the WISE study can be enrolled into this ancillary study if they meet the study criteria. Women not enrolled in the WISE study can also be entered into this ancillary study as long as they too meet the study criteria. After WISE evaluations document reduced coronary blood flow reserve (<3.0 velocity), patients will be randomized to double-blind placebo or quinapril (started at 40 mg/d and titrated to 80 mg/d by the end of the first week). After treatment on the maximum tolerated dose for 16 weeks, patients will be reevaluated with stress testing, brachial artery ultrasound, coronary angiogram with coronary flow reserve, and P-31 NMR.

Intervention(s) in this Clinical Trial

• Drug: Quinapril or placebo

Primary Measures

• Absolute value in coronary flow reserve at Week 16.

Secondary Measures

• Measurements at Week 16 change in:
• •Percent flow mediated brachial artery dilation by ultrasound.
• •Myocardial ischemia as measured by P31 MR spectroscopy (PCr/ATP and Pi/PCr ratios; pH).
• •Total exercise duration as measured by Modified ACIP ETT.
• •Chest pain as measured by a Seattle Angina Questionnaire.

Inclusion Criteria:

• 1. Non pregnant women with chest discomfort 21 to 75 years of age from diverse racial/ethnic groups.
• 2. Suspected IHD but no severe coronary stenosis (> 50% diameter reduction) on coronary angiography used to qualify for WISE.
• 3. Coronary flow reserve limitation (<3.0 velocity or 3.0 volumetric).

Exclusion Criteria:

• 1. 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 providing this therapy remains constant throughout the study.
• If a patient becomes pregnant or begins breast-feeding during the study, she must be withdrawn immediately.
• 2. Acute ischemic syndrome defined as acute MI (by enzyme or ECG criteria) or unstable angina within 1 month of entry.
• 3. 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 kept on that dosing regimen throughout participation in the study.
• 4. Severe heart failure defined as NYHA Class III or IV on treatment.
• 5. Coronary revascularization by either CABG or PTCA or Stent Placement.
• 6. Conditions likely to influence outcomes independent of IHD: Severe lung, renal (creatinine >3.0) or hepatic disease, surgically uncorrected significant congenital or valvular heart disease and other disease likely to be fatal or require frequent hospitalization within the next six months.
• 7. 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, unwilling to complete follow-up evaluation including repeat testing.
• 8. Hypersensitivity to any medications to be used in the study (e.g. angioedema to ACE-I).
• 9. Documented obstructive hypertrophic cardiomyopathy.
• 10. Aortic stenosis (valve area <1.5cm).
• 11. LV dysfunction (ejection fraction 35%).
• 12. History of cocaine or amphetamine abuse.
• 13. ACE-I or AT-1 receptor blocker use within 30 days or need for continued ACEI/AT-1RB use.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Florida

Overall Clinical Trial Officials and Contacts

Carl J Pepine, MD Principal Investigator University of Florida  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00150826

Study ID Number: QWISE

ClinicalTrials.gov Identifier: NCT00150826

Health Authority: United States: Institutional Review Board