Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD
WARRIOR
5 other identifiers
interventional
2,476
2 countries
81
Brief Summary
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 was planned to 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). The number of sites were increased and follow up was modified to continue until the last patient enrolled was followed until trial follow up was completed. Recruitment was complete January 6, 2024. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 coronary-artery-disease
Started Feb 2018
Longer than P75 for phase_4 coronary-artery-disease
81 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 24, 2018
CompletedFirst Posted
Study publicly available on registry
January 31, 2018
CompletedStudy Start
First participant enrolled
February 9, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 14, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 14, 2026
February 19, 2026
February 1, 2026
8.6 years
January 24, 2018
February 18, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The primary outcome is MACE, defined as first occurrence of all-cause death, non-fatal MI, non-fatal stroke, or hospitalization for angina or HF.
All-cause death will be used 1) CV death is insensitive in this population with non-obstructive CAD since death is less likely attributed to CV causes when no obstructive CAD is present; 2) all-cause death is resistant to ascertainment bias in this unblinded trial. CV death will be defined broadly to include both definite CV death and possible CV death (all deaths except those with definite non-CV cause, e.g., cancer, witnessed trauma and homicide). The MI definition follows universal criteria for Types 1-5 MI events. Stroke/TIA definition is new onset neurological defect of central origin confirmed by brain imaging (CT or MRI) evidence of cerebral infarction or intracerebral hemorrhage. Hospitalization for angina- Any hospitalization for angina, plus unstable angina or ACS. Hospitalization for Heart Failure -required established objective criteria for heart failure. All MACE events are adjudicated by a blinded Clinical Endpoint Committee
Within 5 years
Secondary Outcomes (12)
Components of MACE
Within 5 years
Composite hierarchical MACE endpoint
Within 5 years
Seattle Angina Questionnaire (SAQ).
Study entry and every six months until end of follow up (up to 72 months)
EQ-5D-3L
Study entry and every six months until end of follow up (up to 72 months)
Duke Activity Status Inventory (DASI)
Study entry and every six months until end of follow up (up to 72 months)
- +7 more secondary outcomes
Other Outcomes (1)
An analysis of MACE with repeated events considering the number of previous events as a time-dependent covariate will be performed
Within 5 years
Study Arms (2)
Intensive Medical Treatment (IMT)
EXPERIMENTALThe 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.
Usual Care (UC)
ACTIVE COMPARATORThe 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.
Interventions
The IMT-assigned women will receive high-dose, potent statin (atorvastatin 40-80 mg/d or rosuvastatin 20-40mg) class of lipid-lowering medications.
Will be recommended to IMT women without contraindications or bleeding risk.
The PACE Lifestyle Assessment Intervention which is a program to assist with smoking cessation, weight loss, and exercise.
Quality of Life Questionnaires will be obtained.
Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are widely prescribed for primary hypertension.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Floridalead
- United States Department of Defensecollaborator
Study Sites (81)
Cardiology Associates of Mobile, Inc.
Mobile, Alabama, 36608, United States
Dignity Health-Mercy Gilbert Medical Center
Gilbert, Arizona, 85297, United States
Dignity Health-St. Joseph
Phoenix, Arizona, 85013, United States
University of Arizona
Tucson, Arizona, 85721, United States
University of Arkansas
Little Rock, Arkansas, 72205, United States
Cedars-Sinai Heart Institute
Los Angeles, California, 90048, United States
UCLA Medical Center
Los Angeles, California, 90095, United States
Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
Torrance, California, 90502, United States
Georgetown University
Washington D.C., District of Columbia, 20057, United States
Clearwater Cardiovascular Consultants Clinical Research
Clearwater, Florida, 33756, United States
South Palm Cardiovascular Research Institute
Delray Beach, Florida, 33446, United States
Family Medicine at Eastside Community Practice
Gainesville, Florida, 32206, United States
Family Medicine at Hampton Oaks Medical Plaza (Adults and Peds)
Gainesville, Florida, 32607, United States
Internal Medicine at Tower Hill
Gainesville, Florida, 32607, United States
Family Medicine at Haile Plantation (Adults & Peds)
Gainesville, Florida, 32608, United States
Malcom Randall VA Medical Center
Gainesville, Florida, 32608, United States
Cardiovascular Clinic at UF Health UF
Gainesville, Florida, 32610, United States
Internal Medicine at UF Health Medical Plaza
Gainesville, Florida, 32610, United States
Spring Hill Cardiology
Gainesville, Florida, 32610, United States
Family Medicine at 4th Ave
Gainesville, Florida, 32611, United States
Family Medicine at Old Town (Adults and Peds)
Gainesville, Florida, 32680, United States
Baptist Health
Jacksonville, Florida, 32207, United States
University of Florida, Jacksonville
Jacksonville, Florida, 32209, United States
Naval Hospital Jacksonville
Jacksonville, Florida, 32214, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
UF Primary Care at Lake City SW
Lake City, Florida, 32024, United States
UF Primary Care at Lake City West
Lake City, Florida, 32024, United States
Charles H. Croft MDPA
Melbourne, Florida, 32901, United States
Daytona Heart Group
Multiple Locations, Florida, 32114, United States
Southwest Florida Research Institute
Naples, Florida, 34102, United States
Cardiovascular Instititute of Central Florida
Ocala, Florida, 34471, United States
Ocala Research Institute Inc.
Ocala, Florida, 34480, United States
Orlando Health
Orlando, Florida, 32806, United States
Naval Hospital Pensacola
Pensacola, Florida, 32512, United States
Cardiovascular Center of Sarasota
Sarasota, Florida, 34239, United States
Advent Sebring
Sebring, Florida, 33872, United States
James A. Haley Veterans Hospital
Tampa, Florida, 33612, United States
AdventHealth Tampa - Pepin Heart Institute
Tampa, Florida, 33613, United States
Interventional Cardiac Consultants
Tampa, Florida, 33613, United States
BayCare Medical Group
Tampa, Florida, 33614, United States
Guardian Research
Winter Park, Florida, 32792, United States
Emory University
Atlanta, Georgia, 30322, United States
Cardiovascular Consultants of South Georgia, LLC.
Thomasville, Georgia, 31792, United States
Loyola University Chicago
Chicago, Illinois, 60660, United States
Medicoricium
Fairview Heights, Illinois, 62208, United States
Carle Foundation Hospital
Urbana, Illinois, 61801, United States
Midwest Cardiovascular Research and Education Foundation
Elkhart, Indiana, 46514, United States
Lutheran Health Physicians
Fort Wayne, Indiana, 46804, United States
Midwest Heart and Vascular Specialists
Overland Park, Kansas, 66211, United States
Western Kentucky Heart And Lung
Bowling Green, Kentucky, 42103, United States
The Research Group of Lexington, LLC
Lexington, Kentucky, 40503, United States
University of Kentucky
Lexington, Kentucky, 40506, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889, United States
Berkshire Medical Center
Pittsfield, Massachusetts, 01201, United States
Mid Michigan Health
Midland, Michigan, 48670, United States
Essentia Institute of Rural Health
Duluth, Minnesota, 55805, United States
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, 55407, United States
Cardiology Associates Research, LLC
Tupelo, Mississippi, 38801, United States
Cardiology Associates Research. LLC
Tupelo, Mississippi, 38801, United States
CHI Health Research Center
Omaha, Nebraska, 68124, United States
Silver State Cardiology
Henderson, Nevada, 89052, United States
The Valley Hospital
Ridgewood, New Jersey, 07450, United States
Bassett Healthcare Network
Cooperstown, New York, 13326, United States
NYU Langone
New York, New York, 10016, United States
Weil Medical college of Cornell
New York, New York, 10065, United States
Jamaica Hospital Medical Center
Richmond Hill, New York, 11418, United States
Peak Clinical Trials, LLC
Apex, North Carolina, 27502, United States
Pinehurst Medical Clinic
Pinehurst, North Carolina, 38274, United States
The Christ Hospital
Cincinnati, Ohio, 45219, United States
Trihealth Heart Institute
Cincinnati, Ohio, 45242, United States
Heart House Research Foundation
Springfield, Ohio, 45505, United States
Seton Heart Institute
Austin, Texas, 78705, United States
Austin Heart
Austin, Texas, 78756, United States
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234, United States
San Antonio Endovascular and Heart Institute
San Antonio, Texas, 78258, United States
Baylor Scott and White
Temple, Texas, 76508, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
Chippenham Hospital
Richmond, Virginia, 23225, United States
Carilion Clinic
Roanoke, Virginia, 24017, United States
West Virginia University
Morgantown, West Virginia, 26508, United States
VA Caribbean Healthcare System
San Juan, 00921, Puerto Rico
Related Publications (2)
Ya'Qoub L, Elgendy IY, Pepine CJ. Non-obstructive Plaque and Treatment of INOCA: More to Be Learned. Curr Atheroscler Rep. 2022 Sep;24(9):681-687. doi: 10.1007/s11883-022-01044-4. Epub 2022 Jul 4.
PMID: 35781776DERIVEDHandberg EM, Merz CNB, Cooper-Dehoff RM, Wei J, Conlon M, Lo MC, Boden W, Frayne SM, Villines T, Spertus JA, Weintraub W, O'Malley P, Chaitman B, Shaw LJ, Budoff M, Rogatko A, Pepine CJ. Rationale and design of the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial. Am Heart J. 2021 Jul;237:90-103. doi: 10.1016/j.ahj.2021.03.011. Epub 2021 Mar 18.
PMID: 33745898DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carl J Pepine, MD
University of Florida
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- The Clinical Events Committee (CEC) will be masked to all treatment assignment.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2018
First Posted
January 31, 2018
Study Start
February 9, 2018
Primary Completion (Estimated)
September 14, 2026
Study Completion (Estimated)
September 14, 2026
Last Updated
February 19, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share