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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00150826
First received: September 6, 2005
Last updated: April 12, 2012
Last verified: April 2012
  Purpose

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


Condition Intervention Phase
Ischemic Heart Disease
Drug: Quinapril
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University of Florida:

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.

Enrollment: 78
Study Start Date: May 2000
Study Completion Date: December 2004
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Quinapril
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.
Drug: Quinapril
Quinapril will be started at 40mg daily and titrated to 80mg daily for 16 weeks.
Placebo Comparator: Placebo
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.
Drug: Placebo
Placebo will be given in a capsule form once daily for 16 weeks.

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.

  Eligibility

Ages Eligible for Study:   21 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Non pregnant women with chest discomfort 21 to 75 years of age from diverse racial/ethnic groups.
  2. Suspected ischemic heart disease (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).

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 myocardial infarction (MI) (by enzyme or electrocardiogram (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 New York Heart Association (NYHA) Class III or IV on treatment.
  5. Coronary revascularization by either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (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 angiotension 1 (AT-1) receptor blocker use within 30 days or need for continued ACEI/AT-1RB use.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00150826

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Carl J Pepine, MD University of Florida
  More Information

Publications:
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00150826     History of Changes
Other Study ID Numbers: QWISE, 5U01HL064924-04
Study First Received: September 6, 2005
Last Updated: April 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
microvascular disease
women
renin angiotensin system
WISE
ischemic heart disease

Additional relevant MeSH terms:
Chest Pain
Coronary Artery Disease
Heart Diseases
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Coronary Disease
Pain
Signs and Symptoms
Vascular Diseases
Quinapril
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014