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QWISE - Study of Quinapril in Women With Chest Pain, Coronary Flow Reserve Limitations and Evidence of Myocardial Ischemia

Primary Purpose

Ischemic Heart Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Quinapril
Placebo
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Heart Disease focused on measuring microvascular disease, women, renin angiotensin system, WISE, ischemic heart disease

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Non pregnant women with chest discomfort 21 to 75 years of age 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. Coronary flow reserve limitation (<3.0 velocity). 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 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 If a patient becomes pregnant or begins breast-feeding during the study, she must be withdrawn immediately. 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 kept 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 >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. 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. Hypersensitivity to any medications to be used in the study (e.g. angioedema to ACE-I). Documented obstructive hypertrophic cardiomyopathy. Aortic stenosis (valve area <1.5cm). LV dysfunction (ejection fraction <=35%). History of cocaine or amphetamine abuse. ACE-I or angiotension 1 (AT-1) receptor blocker use within 30 days or need for continued ACEI/AT-1RB use.

Sites / Locations

  • University of Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Quinapril

Placebo

Arm Description

This arm will receive quinapril which will be started at 40mg daily and titrated to 80mg daily by the end of the first week. After treatment on the maximum tolerated dose for 16 weeks, patients will be reevaluated with coronary angiogram with coronary flow reserve measurements and assessment of angina using the Seattle Angina Questionnaire.

This arm will receive placebo for 16 weeks and will be reevaluated with coronary angiogram with coronary flow reserve measurements and assessment of angina using the Seattle Angina Questionnaire.

Outcomes

Primary Outcome Measures

Adjusted coronary flow reserve at Week 16

Secondary Outcome Measures

Chest pain as measured by a Seattle Angina Questionnaire adjusted for baseline values.

Full Information

First Posted
September 6, 2005
Last Updated
April 12, 2012
Sponsor
University of Florida
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00150826
Brief Title
QWISE - Study of Quinapril in Women With Chest Pain, Coronary Flow Reserve Limitations and Evidence of Myocardial Ischemia
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.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
May 2000 (undefined)
Primary Completion Date
December 2004 (Actual)
Study Completion Date
December 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
INDICATION Microvascular angina. OBJECTIVES To investigate the effect of ACE (angiotensin converting enzyme) inhibition (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) Coronary flow reserve (CFR) at Week 16 adjusted for baseline CFR, treatment group assignment, site-specific variables, and site by treatment effects. SECONDARY EFFICACY PARAMETERS Week 16 change in chest discomfort as measured by the Seattle Angina Questionnaire adjusting for baseline values, site, and site by treatment effects. 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
Detailed Description
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 including symptom assessment using the Seattle Angina Questionnaire (SAQ) and documented 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 coronary angiogram with coronary flow reserve measurements and assessment of angina using the SAQ.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Heart Disease
Keywords
microvascular disease, women, renin angiotensin system, WISE, ischemic heart disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Quinapril
Arm Type
Active Comparator
Arm Description
This arm will receive quinapril which will be started at 40mg daily and titrated to 80mg daily by the end of the first week. After treatment on the maximum tolerated dose for 16 weeks, patients will be reevaluated with coronary angiogram with coronary flow reserve measurements and assessment of angina using the Seattle Angina Questionnaire.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
This arm will receive placebo for 16 weeks and will be reevaluated with coronary angiogram with coronary flow reserve measurements and assessment of angina using the Seattle Angina Questionnaire.
Intervention Type
Drug
Intervention Name(s)
Quinapril
Intervention Description
Quinapril will be started at 40mg daily and titrated to 80mg daily for 16 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be given in a capsule form once daily for 16 weeks.
Primary Outcome Measure Information:
Title
Adjusted coronary flow reserve at Week 16
Secondary Outcome Measure Information:
Title
Chest pain as measured by a Seattle Angina Questionnaire adjusted for baseline values.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Non pregnant women with chest discomfort 21 to 75 years of age 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. Coronary flow reserve limitation (<3.0 velocity). 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 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. 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 kept 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 >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. 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. Hypersensitivity to any medications to be used in the study (e.g. angioedema to ACE-I). Documented obstructive hypertrophic cardiomyopathy. Aortic stenosis (valve area <1.5cm). LV dysfunction (ejection fraction <=35%). History of cocaine or amphetamine abuse. ACE-I or angiotension 1 (AT-1) receptor blocker use within 30 days or need for continued ACEI/AT-1RB use.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carl J Pepine, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21982660
Citation
Pauly DF, Johnson BD, Anderson RD, Handberg EM, Smith KM, Cooper-DeHoff RM, Sopko G, Sharaf BM, Kelsey SF, Merz CN, Pepine CJ. In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE). Am Heart J. 2011 Oct;162(4):678-84. doi: 10.1016/j.ahj.2011.07.011. Epub 2011 Sep 6.
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QWISE - Study of Quinapril in Women With Chest Pain, Coronary Flow Reserve Limitations and Evidence of Myocardial Ischemia

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