The PRECISE Protocol: Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization

Coronary Artery Disease Clinical Trial

— PRECISE  

Official title:

Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03702244
• Other study ID #: CP-907-001-A
• Status: Completed
• Phase: N/A
• Start date: November 27, 2018
• Est. completion date: May 20, 2022

Study information

• Verified date: October 2023
• Source: HeartFlow, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will be a prospective, pragmatic, randomized clinical trial of the comparative effectiveness of diagnostic evaluation strategies for stable CAD, to be performed in outpatient settings, including primary care and cardiology practices.

Description:

Objective was to test a modified initial cCTA strategy (PS) designed to improve clinical efficiency vs usual testing (UT). Patients from 65 North American and European sites with stable symptoms of suspected coronary artery disease (CAD) and no prior testing were randomly assigned 1:1 to precision strategy PS or UT. PS incorporated the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) minimal risk score to quantitatively select minimal-risk participants for deferred testing, assigning all others to cCTA with selective CT-derived fractional flow reserve (FFR-CT). UT included site-selected stress testing or catheterization. Site clinicians determined subsequent care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2103
• Est. completion date: May 20, 2022
• Est. primary completion date: May 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria (all must be present):

1. Age =18 years

2. Stable typical or atypical symptoms suggesting possible significant coronary artery disease (CAD) with further non-emergent testing or elective catheterization recommended to evaluate the presence of suspected significant CAD. Stable chest pain (or equivalent) includes those who have fully been ruled out for Acute Coronary Syndrome (ACS) and for whom elective testing is recommended, regardless of the venue in which they are seen.

3. If prior CV testing has occurred, it must have been performed greater than one year

prior to randomization, and the following must be met:

1. cCTA or invasive coronary angiography (ICA) with stenosis < 50%

2. Quantified coronary artery calcium (CAC) < 100 AG

4. Safe performance of cCTA:

1. Creatinine clearance =45 ml/min per most recent measurement within 90 days

2. For a female participant of childbearing potential (those who have not been surgically sterilized or are not postmenopausal), a pregnancy test must be performed with negative results known within 7 days prior to randomization

5. Willingness to comply with all aspects of the protocol, including adherence to the assigned strategy and follow-up visits

6. Ability to provide written informed consent

Exclusion criteria (all must be absent):

1. Acute chest pain (in patients who have not been ruled out for ACS)

2. Unstable clinical status

3. Noninvasive or invasive CV testing for CAD within 1 year. CV testing for CAD refers to any stress tests, invasive coronary angiography (ICA) and cCTA (including calcium scoring) only. a. Resting ECG, resting echocardiogram and resting CMR (MRI) are not exclusionary regardless of when were performed

4. Lifetime history of known obstructive CAD (prior myocardial infarction, CABG or PCI, stenosis =50%), known EF =40% or other moderate to severe valvular or congenital cardiac disease

5. Contraindications to cCTA including but not limited to creatinine clearance (GFR) <45 ml/min as per most recent measurement taken within 90 days

6. Exceeds the site's weight or size limit for cCTA or cardiac catheterization

7. Any condition leading to possible inability to comply with the protocol procedures or follow-up

8. Any condition that might interfere with the study procedures or follow-up

9. Enrolled in an investigational trial that involves a non-approved cardiac drug or device which has not reached its primary endpoint

10. Life expectancy less than 2 years due to non-cardiovascular comorbidities

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Diagnostic Test:
• cCTA with selective FFRct
PRECISE will evaluate whether a precision evaluation strategy that combines contemporary risk stratification using the PROMISE Risk Tool with functional and anatomic non-invasive evaluation with cCTA with selective FFRct can improve outcomes over usual care in stable chest pain patients while safely deferring further testing in low-risk patients and reducing cost overall

Locations

Country	Name	City	State
United States	Participating site	Lake Charles	Louisiana

Sponsors (3)

Lead Sponsor	Collaborator
HeartFlow, Inc.	Cardiovascular Research Foundation, New York, Duke Clinical Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Composite (Number) of Deaths / MIs / Invasive Coronary Angiography Without Obstructive Disease	The centrally adjudicated (by Clinical Events Committee) primary end point was a composite of clinical efficiency as a gatekeeper to invasive testing (catheterization without obstructive CAD) and safety (death, non fatal myocardial infarction [MI]) at 1 year. Invasive cardiac catheterization without obstructive coronary artery disease defined as the absence of any =50% stenosis or hemodynamic indication of significance (no FFR =0.80 or iFR=0.89) in any major epicardial vessel including side branches =2 mm in diameter, as determined by core-lab adjudicated quantitative coronary angiography (QCA) or if QCA not performed, by site report. A detailed description and information on the definitions of primary endpoint component definitions is provided in the current version of the study Protocol, Statistical Analysis Plan, and the published trial design article.	1 year
Secondary	Number of Unplanned Hospitalizations (Including Admissions With Death or MI)	Urgent and unscheduled hospitalizations for cardiovascular causes include hospitalization for ischemic heart disease including myocardial infarction and unstable angina, cerebrovascular disease including stroke and TIA, heart failure, acute and/or critical limb ischemia, other thrombotic events including pulmonary embolism, arrhythmias, cardiac arrest and other clear cardiovascular causes for hospitalization that do not meet the criteria for the specific events listed here (e.g., hospitalization for acute cardiac chest pain that does not meet the criteria for MI or UA).	1 year
Secondary	Number of Catheterization and Revascularization Procedures	Catheterization efficiency was defined as the proportion of invasive cardiac catheterization patients who undergo revascularization (PCI or CABG) within 6 months. Revascularization may occur either percutaneously (PCI) or surgically (CABG) or as hybrid (PCI and CABG). For PCI, any intervention on a lesion in the coronary tree (including angioplasty, stenting, intravascular lithotripsy) whether successful or not will be considered a revascularization. For CABG the start of the surgical procedure (skin incision) was considered as CABG, whether the procedure was successful or not. Staged revascularization was considered as one revascularization event.	1 year
Secondary	Number of Participants With Preventive Medication Use	Lipid-lowering agents included statins, ezetimibe, PCSK9 inhibitors. Antiplatelet agents included aspirin, clopidogrel, ticagrelor, or prasugrel. Antihypertensive medications included calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin-neprilysin inhibitor, beta blockers, nitrates, or diuretics.	1 Year
Secondary	Number of Participants With Quality of Life (Angina Frequency) Assessment	Overall health status was assessed briefly using the EQ-5D-5L, a standardized generic measure that can also be used to link specific health states to general population-based utilities. The EQ-5D-5L consists of two parts: (1) a descriptive assessment of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can take one of five responses corresponding to the level of severity within each dimension, and (2) a self-rating 0- 100 "thermometer" of current health-related quality of life. The proportion of participants with frequent angina (Seattle Angina Questionnaire angina frequency score <80).	1 year
Secondary	Cumulative Radiation Exposure From All Cardiovascular Procedures (12 M), MilliSievert (mSv)	The cumulative radiation exposure over the 12 months following Randomization was calculated based on each participant's exposure to radiation for cardiovascular care. If data are missing in > 80% or more of the diagnostic and procedural testing, a single fixed estimate of radiation based on the literature will be used to impute. Given high missingness in catheterization data, a fixed estimate of 6.6 mSv and 4.1 mSv was used for catheterization with and without revascularization, respectively, based on recent trial data.	1 year

External Links

•   Comparison of an Initial Risk-Based Testing Strategy vs Usual Testing in Stable Symptomatic Patients With Suspected Coronary Artery Disease The PRECISE Randomized Clinical Trial