Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This will be a PROBE design, that will evaluate an intensive statin/ACE-I (or ARB) treatment strategy (IMT) vs. primary prevention risk factor therapy treatment strategy (UC) in symptomatic (chronic angina or equivalent) women with non-obstructive CAD.
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)
Masking Description
The Clinical Events Committee (CEC) will be masked to all treatment assignment.

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Cardiology Associates of Mobile, Inc.
Mobile, Alabama 36608
Contact:
Ruth Wagner
251-340-6870

University of Arkansas
Little Rock, Arkansas 72205
Contact:
Cindy Witkowski, RN, BSN
501-526-5282
witkowskicynthial@uams.edu

Cedars-Sinai Heart Institute
Los Angeles, California 90048
Contact:
Norma Moy
310-423-7609
NormaPriscilla.Moy@cshs.org

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
Torrance, California 90502

Clearwater Cardiovascular Consultants Clinical Research
Clearwater, Florida 33756

South Palm Cardiovascular Research Institute
Delray Beach, Florida 33446

Family Medicine at Eastside Community Practice
Gainesville, Florida 32206

Family Medicine at Hampton Oaks Medical Plaza (Adults and Peds)
Gainesville, Florida 32607

Internal Medicine at Tower Hill
Gainesville, Florida 32607

Family Medicine at Haile Plantation (Adults & Peds)
Gainesville, Florida 32608

Malcom Randall VA Medical Center
Gainesville, Florida 32608
Contact:
Susan Stinson, BSN
352-548-7422

Cardiovascular Clinic at UF Health UF
Gainesville, Florida 32610

Internal Medicine at UF Health Medical Plaza
Gainesville, Florida 32610

UF Health at the University of Florida
Gainesville, Florida 32610

Cardiology West at Doctors Park
Gainesville, Florida 32611

Family Medicine at 4th Ave
Gainesville, Florida 32611

Family Medicine at Old Town (Adults and Peds)
Gainesville, Florida 32680

Baptist Health
Jacksonville, Florida 32207

University of Florida, Jacksonville
Jacksonville, Florida 32209

Naval Hospital Jacksonville
Jacksonville, Florida 32214

UF Primary Care at Lake City SW
Lake City, Florida 32024

UF Primary Care at Lake City West
Lake City, Florida 32024

Charles H. Croft MDPA
Melbourne, Florida 32901
Contact:
Pauline Talbott
studyprospect@gmail.com

Daytona Heart Group
Multiple Locations, Florida 32114
Contact:
Glenn Rayos, MD
386-258-8722

Southwest Florida Research Institute
Naples, Florida 34102
Contact:
Mike Halbert, Pharm.D.
239-213-0213

Cardiovascular Instititute of Central Florida
Ocala, Florida 34471
Contact:
Hima Mikkilineni, MD

Ocala Research Institute Inc.
Ocala, Florida 34480
Contact:
Rakesh Prashad, MD
352-412-5989

Orlando Health
Orlando, Florida 32806

Naval Hospital Pensacola
Pensacola, Florida 32512

Cardiovascular Center of Sarasota
Sarasota, Florida 34239

Advent Sebring
Sebring, Florida 33872
Contact:
James Leicht
863-414-7004
james.leicht@adventhealth.com

AdventHealth Tampa - Pepin Heart Institute
Tampa, Florida 33613
Contact:
Charles R Lambert, MD
813-615-7527

Interventional Cardiac Consultants
Tampa, Florida 33613
Contact:
Carlos J Bayron, MD
727-842-9526

BayCare Medical Group
Tampa, Florida 33614
Contact:
Pam Paul

Guardian Research
Winter Park, Florida 32792
Contact:
Jessica Gilliam
386-785-2400
jgilliam@accelclinical.com

Cardiovascular Consultants of South Georgia, LLC.
Thomasville, Georgia 31792
Contact:
Shelli Roberts
smroberts@ccsgheart.com

Midwest Cardiovascular Research and Education Foundation
Elkhart, Indiana 46514
Contact:
Vijay Mehta, MD
574-522-0337

Midwest Heart and Vascular Specialists
Overland Park, Kansas 66211
Contact:
Elizabeth Fulks
913-253-3022
Elizabeth.Fulks@hcahealthcare.com

The Research Group of Lexington, LLC
Lexington, Kentucky 40503
Contact:
Stacy Newsome, CCRP
859-977-4005
stacy@researchgrouplexington.com

University of Kentucky
Lexington, Kentucky 40506

Walter Reed National Military Medical Center
Bethesda, Maryland 20889
Contact:
Lauren Weber, MD
301-400-2383
lauren.a.weber3.mil@mail.mil

Essentia Institute of Rural Health
Duluth, Minnesota 55805
Contact:
Kaitlyn Rikkola
218-786-2077
Kaitlyn.Rikkola@EssentiaHealth.org

Minneapolis Heart Institute Foundation
Minneapolis, Minnesota 55407
Contact:
Retu Saxena, MD

Cardiology Associates Research, LLC
Tupelo, Mississippi 38801
Contact:
Tina Watts
662-620-6863
twatts5933@nmhs.net

Cardiology Associates Research. LLC
Tupelo, Mississippi 38801

CHI Health Research Center
Omaha, Nebraska 68124
Contact:
Mel Romsa
402-343-8535

Silver State Cardiology
Henderson, Nevada 89052

Bassett Healthcare Network
Cooperstown, New York 13326
Contact:
Dhananjai Menzies

Jamaica Hospital Medical Center
Richmond Hill, New York 11418
Contact:
Aditya Mangla, MD

Peak Clinical Trials, LLC
Apex, North Carolina 27502
Contact:
Barbara White
919-267-6209

Pinehurst Medical Clinic
Pinehurst, North Carolina 38274
Contact:
Rebecca Meyer
910-235-3144
rmeyer@pinehurstmedical.com

Heart House Research Foundation
Springfield, Ohio 45505

Seton Heart Institute
Austin, Texas 78705
Contact:
Sarah Benedict
512-803-1761

Brooke Army Medical Center
Fort Sam Houston, Texas 78234

San Antonio Endovascular and Heart Institute
San Antonio, Texas 78258
Contact:
Piotr Kunik
pkunik@drkiesz.com

Baylor Scott and White
Temple, Texas 76508
Contact:
Wanda Fikes
254-724-5373

University of Virginia Health System
Charlottesville, Virginia 22908
Contact:
Angela Taylor
434-982-1058

Chippenham Hospital
Richmond, Virginia 23225
Contact:
Stephanie Burton
Stephanie.Burton@HCAhealthcare.com

West Virginia University
Morgantown, West Virginia 26508
Contact:
Melissa Morgan
304-285-1947

VA Caribbean Healthcare System
San Juan, Puerto Rico 00921
Contact:
Yiomarie Ojeda-Rodriguez
787-641-7582

More Details

NCT ID
NCT03417388
Status
Recruiting
Sponsor
University of Florida

Study Contact

Dana D Leach, ARNP-BC
352-273-8933
dana.leach@medicine.ufl.edu

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 ~50 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.