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Trial record 4 of 66 for:    Warrior

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

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ClinicalTrials.gov Identifier: NCT03417388
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : January 27, 2021
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE January 24, 2018
First Posted Date  ICMJE January 31, 2018
Last Update Posted Date January 27, 2021
Actual Study Start Date  ICMJE February 9, 2018
Estimated Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2018)
  • 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).
  • 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).
  • 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.
  • 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.
  • 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD
Official Title  ICMJE Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD
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 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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.
Masking: Single (Outcomes Assessor)
Masking Description:
The Clinical Events Committee (CEC) will be masked to all treatment assignment.
Primary Purpose: Treatment
Condition  ICMJE Coronary Artery Disease
Intervention  ICMJE
  • 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 Name: 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 Name: 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 Name: PACE Lifestyle Intervention
  • Behavioral: Quality of Life Questionnaires
    Quality of Life Questionnaires will be obtained.
    Other Name: QOL
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: High dose potent statin
    • Drug: ACE-I (lisinopril) or ARB (losartan)
    • Drug: Aspirin
    • Behavioral: Lifestyle Counseling
    • Behavioral: Quality of Life Questionnaires
  • 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.
    Intervention: Behavioral: Quality of Life Questionnaires
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2018)
4422
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dana D Leach, ARNP-BC 352-273-8933 dana.leach@medicine.ufl.edu
Contact: Debra Landers 352-273-7901 debra.landers@medicine.ufl.edu
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03417388
Other Study ID Numbers  ICMJE IRB201701142 -A
W81XWH-17-2-0030 ( Other Grant/Funding Number: Department of Defense )
OCR17268 ( Other Identifier: UF OnCore )
IRB201802734 ( Other Identifier: UF IRB + VA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE United States Department of Defense
Investigators  ICMJE
Principal Investigator: Carl J Pepine, MD University of Florida
PRS Account University of Florida
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP