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

HeartFlow

Status: Completed

Conditions: Coronary Artery Disease

Treatments: Diagnostic Test: cCTA with selective FFRct

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03702244

CP-907-001-A

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,103 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,103 participants in 2 patient groups

Usual Care

No Intervention group

Description:

For participants randomized to usual care, the participant's care team will select the specific noninvasive stress test (exercise electrocardiogram, stress nuclear imaging \[including PET\], stress MR, or stress echocardiogram); OR invasive test: (direct to diagnostic catheterization).

Precision evaluation

Other group

Description:

Participants randomized to a precision strategy will be assigned to either guideline-recommended care without immediately planned testing (low risk) or cCTA with selective FFRct (elevated risk) using a risk tool based on pretest clinical characteristics derived from the PROMISE trial and validated in SCOT-HEART trial. Participants assigned to guideline-recommended care without planned testing will be treated with preventive and antianginal medical treatment per guideline recommendations and clinical judgment and followed without testing.

Treatment:

Diagnostic Test: cCTA with selective FFRct