CIRCE: Carotid Intraplaque Neovascularization Combined With Stress Echo

Sponsor

Dr. Amer Johri (Other)

Overall Status

Recruiting

CT.gov ID

NCT05416385

Collaborator

Lantheus Medical Imaging (Industry)

1,500

Enrollment

Locations

Anticipated Duration (Months)

375

Patients Per Site

6.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The root cause of heart attacks and strokes is atherosclerosis, the hardening and thickening of blood vessels due to the presence of "plaque" which is a build-up of fat and cholesterol in the walls of vessels. To diagnose heart disease, patients receive a stress test to find out if they require surgery. Up to 52% of patients receiving an angiogram (surgery) to look at plaque blockages in the heart are found to be normal (no blockage). Patients who are suspected of having heart disease often undergo a stress test, which helps cardiologists decide if the patient has heart disease, but stress tests can give false results. In Ontario alone, 90% are stress tests are found to be normal and patients are sent home with little follow-up. Of these 3-5% (~4,000 patients/year) will have a major cardiovascular event (heart attack, surgery, or death) within 3 years. We need to improve the stress test accuracy to reduce cardiac outcome. We now know that it is not just the total amount of plaque that leads to heart attacks and strokes, but the composition of the plaque that can lead to breakage causing a heart attack. Plaques are soft and fragile, and typically contain fat and small leaky blood vessels within their cores. If we are able to identify patients that have leaky plaques using ultrasound, we may be able to improve the accuracy of stress testing. We propose a study looking at the combination of stress testing (assessing heart function) and neck ultrasound (assessing plaque composition), to identify patients at risk for cardiovascular events (heart attacks and death). We will enrol patients from 6 sites across Canada and follow-them for cardiac outcome for 3 years.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis Cardiovascular Diseases Acute Coronary Syndrome Ischemic Heart Disease Myocardial Infarction Carotid Artery Diseases	Other: Carotid Contrast Enhanced Ultrasound

Detailed Description

Primary Aim: To determine if carotid intraplaque neovascularization score (IPN) combined with stress echo (SE) [IPN+SE] enhances prediction of 3-year major adverse cardiovascular events (MACE) compared to SE alone.

Objectives: 1) The % change in test sensitivity of IPN+SE for predicting 3-year MACE compared with SE alone. 2) The Net Reclassification Improvement (NRI) for MACE will be determined (patients "missed" by the SE, but captured as high risk for MACE by IPN).

Study Design

Study Type:

Observational

Anticipated Enrollment :

1500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Combining Intraplaque Neovascularization With Risk Stratification by Carotid Stress ECHO

Actual Study Start Date :

Aug 16, 2021

Anticipated Primary Completion Date :

Aug 16, 2026

Anticipated Study Completion Date :

Aug 16, 2026

Arms and Interventions

Arm	Intervention/Treatment
Cardiac outpatients Subjects referred for outpatient stress echocardiogram (SE).	Other: Carotid Contrast Enhanced Ultrasound Carotid Contrast-Enhanced Ultrasound (CEUS), a diagnostic ultrasound enhancing agent that opacifies the blood to delineate the vessel walls. Other Names: Contrast injection, DEFINITY®, Perflutren Lipid Microsphere

Arm

Intervention/Treatment

Cardiac outpatients

Subjects referred for outpatient stress echocardiogram (SE).

Other: Carotid Contrast Enhanced Ultrasound

Carotid Contrast-Enhanced Ultrasound (CEUS), a diagnostic ultrasound enhancing agent that opacifies the blood to delineate the vessel walls.

Other Names:

Contrast injection, DEFINITY®, Perflutren Lipid Microsphere

Outcome Measures

Primary Outcome Measures

Our primary outcomes will be the improvement in sensitivity and negative predictive value (NPV). [This is a 5-year study. The outcome follow up for mace will be 3-years from the index date (SE).]
Our primary analysis will compare the sensitivity of an established binary test based on SE alone to a binary test based on SE and plaque assessment (using established thresholds, IPN≥1.25) to predict 3-year MACE.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women >18 years;
Referred for a clinically indicated SE for assessment of ischemia and risk stratification;
Able and willing to give informed consent.

Exclusion Criteria:

Emergency procedure, or active acute coronary syndrome (active chest pain, ischemic electrocardiogram changes, or cardiac enzyme elevation);
Referral for viability, pulmonary hypertension, or valve assessment;
Referral outside of the normal working hours;
History of significant CAD: percutaneous coronary intervention (PCI), coronary artery bypass graft (GABG), or coronary angioplasty;
History of stroke or myocardial infarction (MI);
Known or documented hypersensitivity or allergy to perflutren (DEFINITY® contrast agent);
Known or documented allergy to Polyethylene Glycol (Peg) a component of DEFINITY®;
History of carotid surgery (endarterectomy or stenting);
Any serious medical condition or complication from the stress test that according to the investigator could interfere with the carotid scan or optimal care;
Currently pregnant or breastfeeding;
Previous enrolment into the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Calgary	Calgary	Alberta	Canada	T2N 1N4
2	University of Alberta	Edmonton	Alberta	Canada	T6G 2R3
3	Dalhousie University	Halifax	Nova Scotia	Canada	B3H 3A7
4	Queen's University, Cardiovascular Imaging Network at Queen's (CINQ)	Kingston	Ontario	Canada	K7L 2V7