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History of Changes for Study: NCT03417388
Ischemia-Intensive Medical Treatment Reduces Events in Women With Non-obstructive CAD (WARRIOR)
Latest version (submitted September 14, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 24, 2018 None (earliest Version on record)
2 January 31, 2018 Study Description, Study Status and Arms and Interventions
3 February 12, 2018 Recruitment Status, Study Status, Contacts/Locations, Study Description and Study Identification
4 May 3, 2018 Study Status and Contacts/Locations
5 May 17, 2018 Arms and Interventions, Contacts/Locations, Study Design, Study Status and Study Identification
6 June 13, 2018 Arms and Interventions and Study Status
7 June 21, 2018 Study Status and Study Identification
8 August 14, 2018 Study Status and Contacts/Locations
9 August 31, 2018 Contacts/Locations and Study Status
10 September 19, 2018 Study Status and Contacts/Locations
11 October 2, 2018 Study Status
12 November 1, 2018 Contacts/Locations and Study Status
13 November 6, 2018 Contacts/Locations, Arms and Interventions, Study Description and Study Status
14 November 13, 2018 Contacts/Locations and Study Status
15 November 14, 2018 Contacts/Locations and Study Status
16 November 20, 2018 Eligibility and Study Status
17 December 3, 2018 Study Status, Contacts/Locations and Study Design
18 January 9, 2019 Study Status and Contacts/Locations
19 January 11, 2019 Study Status and Study Identification
20 January 17, 2019 Contacts/Locations and Study Status
21 March 5, 2019 Study Status and Eligibility
22 March 11, 2019 Study Status and Study Identification
23 March 21, 2019 Contacts/Locations, Eligibility and Study Status
24 April 19, 2019 Study Status and Contacts/Locations
25 May 10, 2019 Study Status and Eligibility
26 May 16, 2019 Study Status
27 June 6, 2019 Study Status, Contacts/Locations and Study Identification
28 August 16, 2019 Contacts/Locations, Study Status and Eligibility
29 January 2, 2020 Contacts/Locations and Study Status
30 January 4, 2020 Contacts/Locations and Study Status
31 January 14, 2020 Contacts/Locations and Study Status
32 January 25, 2020 Contacts/Locations and Study Status
33 January 28, 2020 Contacts/Locations and Study Status
34 February 13, 2020 Study Status and Contacts/Locations
35 May 27, 2020 Contacts/Locations, Study Status and Eligibility
36 September 3, 2020 Contacts/Locations and Study Status
37 January 26, 2021 Study Status and Contacts/Locations
38 August 11, 2021 Study Status, Study Description and Study Identification
39 September 14, 2021 Contacts/Locations and Study Status
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Study NCT03417388
Submitted Date:  January 24, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: IRB201701142 -A
Brief Title: Ischemia-Intensive Medical Treatment Reduces Events in Women With Non-obstructive CAD (WARRIOR)
Official Title: Ischemia-Intensive Medical Treatment Reduces Events in Women With Non-obstructive CAD Working Title: Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD
Secondary IDs: PR161603 [Other Grant/Funding Number: Department of Defense]
Open or close this module Study Status
Record Verification: December 2017
Overall Status: Not yet recruiting
Study Start: February 2, 2018
Primary Completion: December 30, 2021 [Anticipated]
Study Completion: December 30, 2022 [Anticipated]
First Submitted: January 24, 2018
First Submitted that
Met QC Criteria:
January 24, 2018
First Posted: January 31, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
January 24, 2018
Last Update Posted: January 31, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University of Florida
Responsible Party: Sponsor
Collaborators: United States Department of Defense
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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 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 with coronary arteries showing no flow limit obstruction but with cardiac symptoms (i.e., chest pain, shortness of breath) will reduce their 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 women, and ultimately improve their 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. We will use web-based, real-time data entry, and management University of Florida Data Management System (UFDMS) for site selection, screening, patient eligibility confirmation, enrollment, and randomization. Patients 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, if IMT-assigned women are statin intolerant or if LDL<100 is not achieved, a PCSK9 Inhibitor will be made available. Aspirin will also be recommended to IMT women 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.

Open or close this module Conditions
Conditions: Coronary Artery Disease
Keywords: Coronary Angiography
Coronary CT Angiogram
Ischemia
Non-obstructive CAD
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 4
Interventional Study Model: Parallel Assignment
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.
Number of Arms: 2
Masking: Single (Outcomes Assessor)
Allocation: Randomized
Enrollment: 4422 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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). Evolocumab (PCSK9) Inhibitor will be available to women who have an LDL <100, or intolerance to statins. 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: Evolocumab
PCSK9 Inhibitor will be used for women who have a contraindication or intolerance to statin therapy, or fail to achieve LDL<100.
Other Names:
  • PCSK9 Inhibitor
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 their 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: 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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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).
2. 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. 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.
4. 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.
5. 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).
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 100 Years
Sex: Female
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Signs and symptoms of suspected ischemia prompting referral for further evaluation by cardiac catheterization or coronary CT angiogram.
  • Willing to provide written informed consent.
  • Non-obstructive CAD defined as <50% diameter reduction of a major epicardial vessel by invasive angiography or coronary computed tomography angiography within 2 yrs.

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 5 yrs.
  • Life expectancy <3-yrs. due to non-cardiovascular comorbidity.
  • Enrolled in a competing clinical trial.
  • Prior intolerance to both an ACE-I and ARB.
  • Pregnancy (all pre-menopausal females must have negative serum pregnancy test).
Open or close this module Contacts/Locations
Central Contact Person: Trinity J Cromwell, RN
Telephone: 352-273-7901
Email: tcromwell@ufl.edu
Central Contact Backup: Debra Landers
Telephone: 352-273-7901
Email: debra.landers@medicine.ufl.edu
Study Officials: Carl Pepline, MD
Principal Investigator
University of Florida
Locations: United States, Florida
Family Medicine at Eastside Community Practice
Gainesville, Florida, United States, 32206
Family Medicine at Hampton Oaks Medical Plaza (Adults and Peds)
Gainesville, Florida, United States, 32607
Internal Medicine at Tower Hill
Gainesville, Florida, United States, 32607
Family Medicine at Haile Plantation (Adults & Peds)
Gainesville, Florida, United States, 32608
Cardiovascular Clinic at UF Health UF
Gainesville, Florida, United States, 32610
Internal Medicine at UF Health Medical Plaza
Gainesville, Florida, United States, 32610
UF Health at the University of Florida
Gainesville, Florida, United States, 32610
Cardiology West at Doctors Park
Gainesville, Florida, United States, 32611
Family Medicine at 4th Ave
Gainesville, Florida, United States, 32611
Family Medicine at Old Town (Adults and Peds)
Gainesville, Florida, United States, 32680
UF Primary Care at Lake City SW
Lake City, Florida, United States, 32024
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:

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