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

Coronary Artery Disease Clinical Trial

— WARRIOR  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03417388
• Other study ID #: IRB201701142 -A
• Secondary ID: W81XWH-17-2-0030
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: February 9, 2018
• Est. completion date: December 30, 2024

Study information

• Verified date: April 2024
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2476
• Est. completion date: December 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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)

Related Conditions & MeSH terms

• Coronary Artery Disease
• Ischemia

Intervention

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.
• ACE-I (lisinopril) or ARB (losartan)
Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are widely prescribed for primary hypertension.
• 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.
• Quality of Life Questionnaires
Quality of Life Questionnaires will be obtained.

Locations

Country	Name	City	State
Puerto Rico	VA Caribbean Healthcare System	San Juan
United States	Peak Clinical Trials, LLC	Apex	North Carolina
United States	Emory University	Atlanta	Georgia
United States	Austin Heart	Austin	Texas
United States	Seton Heart Institute	Austin	Texas
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Western Kentucky Heart And Lung	Bowling Green	Kentucky
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Loyola University Chicago	Chicago	Illinois
United States	The Christ Hospital	Cincinnati	Ohio
United States	Trihealth Heart Institute	Cincinnati	Ohio
United States	Clearwater Cardiovascular Consultants Clinical Research	Clearwater	Florida
United States	Bassett Healthcare Network	Cooperstown	New York
United States	South Palm Cardiovascular Research Institute	Delray Beach	Florida
United States	Essentia Institute of Rural Health	Duluth	Minnesota
United States	Midwest Cardiovascular Research and Education Foundation	Elkhart	Indiana
United States	Medicoricium	Fairview Heights	Illinois
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Lutheran Health Physicians	Fort Wayne	Indiana
United States	Cardiovascular Clinic at UF Health UF	Gainesville	Florida
United States	Family Medicine at 4th Ave	Gainesville	Florida
United States	Family Medicine at Eastside Community Practice	Gainesville	Florida
United States	Family Medicine at Haile Plantation (Adults & Peds)	Gainesville	Florida
United States	Family Medicine at Hampton Oaks Medical Plaza (Adults and Peds)	Gainesville	Florida
United States	Family Medicine at Old Town (Adults and Peds)	Gainesville	Florida
United States	Internal Medicine at Tower Hill	Gainesville	Florida
United States	Internal Medicine at UF Health Medical Plaza	Gainesville	Florida
United States	Malcom Randall VA Medical Center	Gainesville	Florida
United States	Spring Hill Cardiology	Gainesville	Florida
United States	Dignity Health-Mercy Gilbert Medical Center	Gilbert	Arizona
United States	Silver State Cardiology	Henderson	Nevada
United States	Baptist Health	Jacksonville	Florida
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Naval Hospital Jacksonville	Jacksonville	Florida
United States	University of Florida, Jacksonville	Jacksonville	Florida
United States	UF Primary Care at Lake City SW	Lake City	Florida
United States	UF Primary Care at Lake City West	Lake City	Florida
United States	The Research Group of Lexington, LLC	Lexington	Kentucky
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas	Little Rock	Arkansas
United States	Cedars-Sinai Heart Institute	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	Charles H. Croft MDPA	Melbourne	Florida
United States	Mid Michigan Health	Midland	Michigan
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Cardiology Associates of Mobile, Inc.	Mobile	Alabama
United States	West Virginia University	Morgantown	West Virginia
United States	Daytona Heart Group	Multiple Locations	Florida
United States	Southwest Florida Research Institute	Naples	Florida
United States	NYU Langone	New York	New York
United States	Weil Medical college of Cornell	New York	New York
United States	Cardiovascular Instititute of Central Florida	Ocala	Florida
United States	Ocala Research Institute Inc.	Ocala	Florida
United States	CHI Health Research Center	Omaha	Nebraska
United States	Orlando Health	Orlando	Florida
United States	Midwest Heart and Vascular Specialists	Overland Park	Kansas
United States	Naval Hospital Pensacola	Pensacola	Florida
United States	Dignity Health-St. Joseph	Phoenix	Arizona
United States	Pinehurst Medical Clinic	Pinehurst	North Carolina
United States	Berkshire Medical Center	Pittsfield	Massachusetts
United States	Chippenham Hospital	Richmond	Virginia
United States	Jamaica Hospital Medical Center	Richmond Hill	New York
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Carilion Clinic	Roanoke	Virginia
United States	San Antonio Endovascular and Heart Institute	San Antonio	Texas
United States	Cardiovascular Center of Sarasota	Sarasota	Florida
United States	Advent Sebring	Sebring	Florida
United States	Heart House Research Foundation	Springfield	Ohio
United States	AdventHealth Tampa - Pepin Heart Institute	Tampa	Florida
United States	BayCare Medical Group	Tampa	Florida
United States	Interventional Cardiac Consultants	Tampa	Florida
United States	James A. Haley Veterans Hospital	Tampa	Florida
United States	Baylor Scott and White	Temple	Texas
United States	Cardiovascular Consultants of South Georgia, LLC.	Thomasville	Georgia
United States	Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center	Torrance	California
United States	University of Arizona	Tucson	Arizona
United States	Cardiology Associates Research, LLC	Tupelo	Mississippi
United States	Cardiology Associates Research. LLC	Tupelo	Mississippi
United States	Carle Foundation Hospital	Urbana	Illinois
United States	Georgetown University	Washington	District of Columbia
United States	Guardian Research	Winter Park	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	United States Department of Defense

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All Cause Death incidents reported between the two groups	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
Primary	Non-fatal myocardial infarction (MI) incidents reported between the two groups	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
Primary	Stroke/TIA incidents reported between the two groups	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
Primary	Hospitalizations for cardiovascular events reported between the two groups	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
Primary	Hospitalizations for heart failure incidents reported between the two groups	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