Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR)

April 18, 2024 updated by: University of Florida

The Ischemia-IMT (Ischemia-Intensive Medical Treatment Reduces Events in Women with Non-Obstructive CAD), subtitle: Women's Ischemia Trial to Reduce Events in Non-Obstructive CAD (WARRIOR) trial is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) evaluating intensive statin/ACE-I (or ARB)/aspirin treatment (IMT) vs. usual care (UC) in 4,422 symptomatic women patients with symptoms and/or signs of ischemia but no obstructive CAD. The hypothesis is that IMT will reduce major adverse coronary events (MACE) 20% vs. UC. The primary outcome is first occurrence of MACE as death, nonfatal MI, nonfatal stroke/transient ischemic attack (TIA) or hospitalization for heart failure or angina. Secondary outcomes include quality of life, time to "return to duty"/work, health resource consumption, angina, cardiovascular (CV) death and primary outcome components. Events will be adjudicated by an experienced Clinical Events Committee (CEC). Follow-up will be 3-years using 50 sites: primarily VA and Active Duty Military Hospitals/Clinics and a National Patient-Centered Clinical Research Network (PCORnet) clinical data research network (CDRN)(OneFlorida Consortium).

This study is being conducted to determine whether intensive medication treatment to modify risk factors and vascular function in women patients with coronary arteries showing no flow limit obstruction but with cardiac symptoms (i.e., chest pain, shortness of breath) will reduce the patient's likelihood of dying, having a heart attack, stroke/TIA or being hospitalized for cardiac reasons. The results will provide evidence data necessary to inform future guidelines regarding how best to treat this growing population of patients, and ultimately improve the patient's cardiac health and quality of life and reduce health-care costs.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

WARRIOR trial is a multi-site, PROBE design, that will evaluate an intensive statin/ACE-I (or ARB)/aspirin treatment strategy (IMT) vs. primary prevention risk factor therapy treatment strategy (UC) in 4,422 symptomatic (chronic angina or equivalent) women with non-obstructive CAD (<50% diameter narrowing).

There will be ~80 US sites, including VA/ military and OneFlorida CDRN sites, with a proven record in prior trials. The investigators will use web-based, real-time data entry, and management University of Florida Data Management System (UFDMS) for site selection, screening, participant eligibility confirmation, enrollment, and randomization. Participants will be recruited from screened women with symptoms suspected to be ischemic with non-obstructive CAD by invasive coronary angiogram or CT angiogram. The high dose statin (atorvastatin or rosuvastatin) and ACE-I (lisinopril) [or ARB (losartan)] are generic commonly used medications previously demonstrated effective for improving angina, stress testing, myocardial perfusion and coronary microvascular flow reserve in small size trials in this population. Additionally, aspirin will also be recommended to IMT participants without contraindications or excess bleeding risk, however aspirin will not be provided by the study. Both the groups will also receive Lifestyle Counseling (PACE Assessment), and the same visit schedule and "face-time" with site staff to reduce bias. Events will be adjudicated by the Clinical Events Committee (CEC), according to objective criteria and masked to treatment assignment clues.

Study Type

Interventional

Enrollment (Actual)

2476

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00921
        • VA Caribbean Healthcare System
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36608
        • Cardiology Associates of Mobile, Inc.
    • Arizona
      • Gilbert, Arizona, United States, 85297
        • Dignity Health-Mercy Gilbert Medical Center
      • Phoenix, Arizona, United States, 85013
        • Dignity Health-St. Joseph
      • Tucson, Arizona, United States, 85721
        • University of Arizona
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Heart Institute
      • Torrance, California, United States, 90502
        • Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Georgetown University
    • Florida
      • Clearwater, Florida, United States, 33756
        • Clearwater Cardiovascular Consultants Clinical Research
      • Delray Beach, Florida, United States, 33446
        • South Palm Cardiovascular Research Institute
      • Gainesville, Florida, United States, 32608
        • Malcom Randall VA Medical Center
      • Gainesville, Florida, United States, 32610
        • Cardiovascular Clinic at UF Health UF
      • Gainesville, Florida, United States, 32206
        • Family Medicine at Eastside Community Practice
      • Gainesville, Florida, United States, 32607
        • Family Medicine at Hampton Oaks Medical Plaza (Adults and Peds)
      • Gainesville, Florida, United States, 32607
        • Internal Medicine at Tower Hill
      • Gainesville, Florida, United States, 32608
        • Family Medicine at Haile Plantation (Adults & Peds)
      • Gainesville, Florida, United States, 32610
        • Internal Medicine at UF Health Medical Plaza
      • Gainesville, Florida, United States, 32610
        • Spring Hill Cardiology
      • Gainesville, Florida, United States, 32611
        • Family Medicine at 4th Ave
      • Gainesville, Florida, United States, 32680
        • Family Medicine at Old Town (Adults and Peds)
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Jacksonville
      • Jacksonville, Florida, United States, 32209
        • University of Florida, Jacksonville
      • Jacksonville, Florida, United States, 32207
        • Baptist Health
      • Jacksonville, Florida, United States, 32214
        • Naval Hospital Jacksonville
      • Lake City, Florida, United States, 32024
        • UF Primary Care at Lake City SW
      • Lake City, Florida, United States, 32024
        • UF Primary Care at Lake City West
      • Melbourne, Florida, United States, 32901
        • Charles H. Croft MDPA
      • Multiple Locations, Florida, United States, 32114
        • Daytona Heart Group
      • Naples, Florida, United States, 34102
        • Southwest Florida Research Institute
      • Ocala, Florida, United States, 34471
        • Cardiovascular Instititute of Central Florida
      • Ocala, Florida, United States, 34480
        • Ocala Research Institute Inc.
      • Orlando, Florida, United States, 32806
        • Orlando Health
      • Pensacola, Florida, United States, 32512
        • Naval Hospital Pensacola
      • Sarasota, Florida, United States, 34239
        • Cardiovascular Center of Sarasota
      • Sebring, Florida, United States, 33872
        • Advent Sebring
      • Tampa, Florida, United States, 33612
        • James A. Haley Veterans Hospital
      • Tampa, Florida, United States, 33614
        • BayCare Medical Group
      • Tampa, Florida, United States, 33613
        • AdventHealth Tampa - Pepin Heart Institute
      • Tampa, Florida, United States, 33613
        • Interventional Cardiac Consultants
      • Winter Park, Florida, United States, 32792
        • Guardian Research
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
      • Thomasville, Georgia, United States, 31792
        • Cardiovascular Consultants of South Georgia, LLC.
    • Illinois
      • Chicago, Illinois, United States, 60660
        • Loyola University Chicago
      • Fairview Heights, Illinois, United States, 62208
        • Medicoricium
      • Urbana, Illinois, United States, 61801
        • Carle Foundation Hospital
    • Indiana
      • Elkhart, Indiana, United States, 46514
        • Midwest Cardiovascular Research and Education Foundation
      • Fort Wayne, Indiana, United States, 46804
        • Lutheran Health Physicians
    • Kansas
      • Overland Park, Kansas, United States, 66211
        • Midwest Heart and Vascular Specialists
    • Kentucky
      • Bowling Green, Kentucky, United States, 42103
        • Western Kentucky Heart And Lung
      • Lexington, Kentucky, United States, 40506
        • University of Kentucky
      • Lexington, Kentucky, United States, 40503
        • The Research Group of Lexington, LLC
    • Maryland
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Pittsfield, Massachusetts, United States, 01201
        • Berkshire Medical Center
    • Michigan
      • Midland, Michigan, United States, 48670
        • Mid Michigan Health
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • Essentia Institute of Rural Health
      • Minneapolis, Minnesota, United States, 55407
        • Minneapolis Heart Institute Foundation
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • Cardiology Associates Research, LLC
      • Tupelo, Mississippi, United States, 38801
        • Cardiology Associates Research. LLC
    • Nebraska
      • Omaha, Nebraska, United States, 68124
        • CHI Health Research Center
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Silver State Cardiology
    • New Jersey
      • Ridgewood, New Jersey, United States, 07450
        • The Valley Hospital
    • New York
      • Cooperstown, New York, United States, 13326
        • Bassett Healthcare Network
      • New York, New York, United States, 10016
        • NYU Langone
      • New York, New York, United States, 10065
        • Weil Medical college of Cornell
      • Richmond Hill, New York, United States, 11418
        • Jamaica Hospital Medical Center
    • North Carolina
      • Apex, North Carolina, United States, 27502
        • Peak Clinical Trials, LLC
      • Pinehurst, North Carolina, United States, 38274
        • Pinehurst Medical Clinic
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • The Christ Hospital
      • Cincinnati, Ohio, United States, 45242
        • Trihealth Heart Institute
      • Springfield, Ohio, United States, 45505
        • Heart House Research Foundation
    • Texas
      • Austin, Texas, United States, 78705
        • Seton Heart Institute
      • Austin, Texas, United States, 78756
        • Austin Heart
      • Fort Sam Houston, Texas, United States, 78234
        • Brooke Army Medical Center
      • San Antonio, Texas, United States, 78258
        • San Antonio Endovascular and Heart Institute
      • Temple, Texas, United States, 76508
        • Baylor Scott and White
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
      • Richmond, Virginia, United States, 23225
        • Chippenham Hospital
      • Roanoke, Virginia, United States, 24017
        • Carilion Clinic
    • West Virginia
      • Morgantown, West Virginia, United States, 26508
        • West Virginia University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signs and symptoms of suspected ischemia prompting referral for further evaluation by cardiac catheterization or coronary angiogram or coronary CT angiogram within 5 years from consent
  • Willing to provide written informed consent
  • Non-obstructive CAD defined as 0 to 49% diameter reduction of a major epicardial vessel or a FFR>0.80

Exclusion Criteria:

  • History of noncompliance (with medical therapy, protocol, or follow-up)
  • History of non-ischemic dilated or hypertrophic cardiomyopathy
  • Documented acute coronary syndrome(ACS) within previous 30 days
  • Left ventricular ejection fraction (LVEF) <40%, New York Heart Association heart failure (NYHA HF) class III-IV, or hospitalization for Reduced ejection fraction (HFrEF) within 180 days
  • Stroke within previous 180 days or intracranial hemorrhage at any time
  • End-stage renal disease, on dialysis, or estimated glomerular filtration rate (eGFR) <30 ml/min.
  • Severe valvular disease or likely to require surgery/Transcatheter aortic valve replacement (TVAR) within 3 years
  • Life expectancy <3-yrs. due to non-cardiovascular comorbidity
  • Enrolled in a competing clinical trial
  • Prior intolerance to both an ACE-I and ARB
  • If intolerant to a statin unless taking a PCSK9 as a statin replacement by their clinical provider
  • Pregnancy (all pre-menopausal females must have negative urine pregnancy test if randomized to IMT before study drugs are prescribed. If they have not gone through menopause, had a hysterectomy, oophorectomy, or sterilization such as tubal ligation procedure)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intensive Medical Treatment (IMT)
The IMT-assigned women will receive high dose potent statin, and moderate dose of an ACE-I (lisinopril) or ARB (losartan). Aspirin will also be recommended to IMT women without contraindications or bleeding risk. This group will also receive Lifestyle Counseling (PACE Assessment), Quality of Life questionnaires, and the same visit schedule and "face-time" with site staff to reduce bias.
Drug: High dose potent statin
The IMT-assigned women will receive high-dose, potent statin (atorvastatin 40-80 mg/d or rosuvastatin 20-40mg) class of lipid-lowering medications.
Other Names:
  • atorvastatin or rosuvastatin
Drug: ACE-I (lisinopril) or ARB (losartan)
Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are widely prescribed for primary hypertension.
Other Names:
  • ACE-I or ARB
Drug: Aspirin
Will be recommended to IMT women without contraindications or bleeding risk.
Behavioral: Lifestyle Counseling
The PACE Lifestyle Assessment Intervention which is a program to assist with smoking cessation, weight loss, and exercise.
Other Names:
  • PACE Lifestyle Intervention
Behavioral: Quality of Life Questionnaires
Quality of Life Questionnaires will be obtained.
Other Names:
  • QOL
Active Comparator: Usual Care (UC)
The UC-assigned women will maintain standard of care. This group will also receive Lifestyle Counseling (PACE Assessment), Quality of Life questionnaires, and the same visit schedule and "face-time" with site staff to reduce bias.
Behavioral: Quality of Life Questionnaires
Quality of Life Questionnaires will be obtained.
Other Names:
  • QOL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All Cause Death incidents reported between the two groups
Time Frame: 3 years
Collection of all deaths reported between the two groups will use the log rank test for comparison of outcomes. Although the power analysis required the exponential assumption, the actual statistical test is free of assumptions, as the null hypothesis is that the survival distributions for the two strategies are the same, and therefore the null hazard ratio is 1.00 (proportional hazards).
3 years
Non-fatal myocardial infarction (MI) incidents reported between the two groups
Time Frame: 3 years
Collection of all non-fatal MI's reported between the two groups will use the log rank test for comparison of outcomes. Although the power analysis required the exponential assumption, the actual statistical test is free of assumptions, as the null hypothesis is that the survival distributions for the two strategies are the same, and therefore the null hazard ratio is 1.00 (proportional hazards). MI definition follows universal criteria for Types 1-5 MI events. Specifically, the use of the "Third Universal Definition of Myocardial Infarction" detection of a rise and/or fall of cardiac biomarker values, with at least one value >99th percentile upper reference limit and preferred biomarker is Cardiac troponin (cTn).
3 years
Stroke/TIA incidents reported between the two groups
Time Frame: 3 years
Collection of all strokes or transient ischemic attack (TIA) reported between the two groups will use the log rank test for comparison of outcomes. Although the power analysis required the exponential assumption, the actual statistical test is free of assumptions, as the null hypothesis is that the survival distributions for the two strategies are the same, and therefore the null hazard ratio is 1.00 (proportional hazards). The stroke definition is new onset neurological defect of central origin confirmed by brain imaging (CT or MRI) evidence of cerebral infarction or intracerebral hemorrhage. The definition of TIA is the same as stroke except no confirmation by brain imaging, but confirmed by a neurologist consult.
3 years
Hospitalizations for cardiovascular events reported between the two groups
Time Frame: 3 years
Collection of all hospitalization for cardiovascular events reported between the two groups will use the log rank test for comparison of outcomes. Although the power analysis required the exponential assumption, the actual statistical test is free of assumptions, as the null hypothesis is that the survival distributions for the two strategies are the same, and therefore the null hazard ratio is 1.00 (proportional hazards). Cardiovascular causes includes accelerated angina, persistent angina, unstable angina.
3 years
Hospitalizations for heart failure incidents reported between the two groups
Time Frame: 3 years
Collection of all hospitalizations for heart failure between the two groups will use the log rank test for comparison of outcomes. Although the power analysis required the exponential assumption, the actual statistical test is free of assumptions, as the null hypothesis is that the survival distributions for the two strategies are the same, and therefore the null hazard ratio is 1.00 (proportional hazards).
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Carl J Pepine, MD, University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 9, 2018

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

January 24, 2018

First Submitted That Met QC Criteria

January 24, 2018

First Posted (Actual)

January 31, 2018

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB201701142 -A
  • W81XWH-17-2-0030 (Other Grant/Funding Number: Department of Defense)
  • OCR17268 (Other Identifier: UF OnCore)
  • IRB201802734 (Other Identifier: UF IRB + VA)
  • IRB201701434 (Other Identifier: UF IRB-01)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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