Clinical trial NCT04680338: Early Detection of Silent Myocardial Ischemia
Official title: Early Detection of Silent Myocardial Ischemia and Cardiac Dysfunction in Asymptomatic Individuals With Increased Coronary Artery Calcium Scores
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ischemic Heart Disease
Silent Myocardial Ischemia
Cardiovascular Diseases
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2020-12-22
Enrollment: 1400
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Early-Synergy investigates a diagnostic imaging approach in asymptomatic individuals from the general population for early detection of silent myocardial ischemia and cardiac dysfunction. The diagnostic imaging approach consists of cardiac computed tomography for coronary artery calcium scoring (CT-CAC) and cardiac magnetic resonance (CMR) stress perfusion imaging. Early-Synergy investigates the effect of early detection of silent myocardial ischemia and cardiac dysfunction by CMR in asymptomatic individuals with increased CAC. In addition, the diagnostic yield of CMR for early detection of silent myocardial ischemia and cardiac dysfunction is investigated. Asymptomatic individuals at increased risk (CAC ≥ 300) are therefore randomized 1:1 to either CMR stress perfusion imaging or a control group.

Detailed description: Early-Synergy is a prospective multi-center study performed in the Netherlands. Potential candidates for participation in Early-Synergy have had CT-CAC scanning as part of participation in two ongoing population-based studies (ROBINSCA and ImaLife) and had CAC ≥300.

Participants are randomized in a 1:1 fashion to (1.) CMR stress perfusion imaging with feedback of clinically actionable findings or (2.) control group.

In the CMR group, feedback on CMR stress perfusion imaging is provided to the participant and general practitioner only in case of CMR findings that require further management based on current clinical guidelines. Participants in the control group will not receive stress CMR perfusion imaging but will be followed in time to evaluate the clinical presentation of the natural course of coronary atherosclerosis.

Follow-up will be performed up to 5 years in both groups by sending questionnaires and collecting medical information from health care providers and registries. Additionally, blood is drawn from participants in the CMR group during the hospital visit for CMR scanning and is stored to allow evaluation of cardiac blood markers as predictors of CMR findings.

Eligibility criteria: Inclusion Criteria:

* Participation in ROBINSCA or ImaLife study
* CT-CAC ≥300

Exclusion Criteria:

* History of ischemic heart disease or other cardiac disease (myocardial infarction, sudden cardiac arrest, heart failure, cardiomyopathy, congenital cardiac disease, percutaneous coronary intervention, coronary artery bypass grafting surgery, valvular surgery, other major cardiac surgery (e.g. cardiac transplantation) and/or previous invasive coronary angiography or catheter ablation)
* Contra-indication for stress CMR perfusion imaging (claustrophobia, CMR incompatible device (e.g., Implantable Cardioverter Defibrillator/pacemaker), contrast agent or vasodilator intolerance, contra-indications for adenosine or regadenoson (e.g. 2nd/3rd degree atrioventricular block, severe hypotension) and/or weight \> 125 kg)
* Severe comorbidity and/or a life expectancy of less than 1 year
* Unable to provide written informed consent
* Pregnancy

Primary outcomes:
measure: Rate of major adverse cardiac events
timeFrame: 1 year
measure: Rate of major adverse cardiac events
timeFrame: 2.5 years
measure: Rate of major adverse cardiac events
timeFrame: 5 years
measure: Diagnostic yield of CMR stress perfusion imaging
timeFrame: Baseline
Secondary outcomes:
measure: Rate of individual components of primary outcome 1
timeFrame: 1 year
measure: Rate of individual components of primary outcome 1
timeFrame: 2.5 years
measure: Rate of individual components of primary outcome 1
timeFrame: 5 years
measure: All-cause mortality rate
timeFrame: 1 year
measure: All-cause mortality rate
timeFrame: 2.5 years
measure: All-cause mortality rate
timeFrame: 5 years
measure: Rate of invasive cardiovascular procedures
timeFrame: 1 year
measure: Rate of invasive cardiovascular procedures
timeFrame: 2.5 years
measure: Rate of invasive cardiovascular procedures
timeFrame: 5 years
measure: Rate of hospitalization for cardiovascular disease
timeFrame: 1, 2.5, 5 years
measure: Rate of hospitalization for cardiovascular disease
timeFrame: 1 year
measure: Rate of hospitalization for cardiovascular disease
timeFrame: 2.5 years
measure: Rate of non-invasive cardiac imaging procedures
timeFrame: 5 years
measure: Rate of medical therapy initiation
timeFrame: 1 year
measure: Rate of medical therapy initiation
timeFrame: 2.5 years
measure: Rate of medical therapy initiation
timeFrame: 5 years
measure: Quality of Life as reflected by EQ-5D-5S score
timeFrame: 1 year
measure: Quality of Life as reflected by EQ-5D-5S score
timeFrame: 2.5 years
measure: Quality of Life as reflected by EQ-5D-5S score
timeFrame: 5 years
measure: Quality of Life as reflected by HeartQoL score
timeFrame: 1 year
measure: Quality of Life as reflected by HeartQoL score
timeFrame: 2.5 years
measure: Quality of Life as reflected by HeartQoL score
timeFrame: 5 years
Other outcomes:
measure: Cost-effectiveness
timeFrame: 1 year
measure: Cost-effectiveness
timeFrame: 2.5 years
measure: Cost-effectiveness
timeFrame: 5 years
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Pim van der Harst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xia C, Rook M, Pelgrim GJ, Sidorenkov G, Wisselink HJ, van Bolhuis JN, van Ooijen PMA, Guo J, Oudkerk M, Groen H, van den Berge M, van der Harst P, Dijkstra H, Vonder M, Heuvelmans MA, Dorrius MD, De Deyn PP, de Bock GH, Dotinga A, Vliegenthart R. Early imaging biomarkers of lung cancer, COPD and coronary artery disease in the general population: rationale and design of the ImaLife (Imaging in Lifelines) Study. Eur J Epidemiol. 2020 Jan;35(1):75-86. doi: 10.1007/s10654-019-00519-0. Epub 2019 Apr 23.
citation: Vonder M, van der Aalst CM, Vliegenthart R, van Ooijen PMA, Kuijpers D, Gratama JW, de Koning HJ, Oudkerk M. Coronary Artery Calcium Imaging in the ROBINSCA Trial: Rationale, Design, and Technical Background. Acad Radiol. 2018 Jan;25(1):118-128. doi: 10.1016/j.acra.2017.07.010. Epub 2017 Aug 23.