Ischemic Heart DiseaseEarlySynergyNCT04680338
Early Detection of Silent Myocardial Ischemia
A study testing CMR stress perfusion imaging in people with Ischemic Heart Disease and Silent Myocardial Ischemia, run by Pim van der Harst at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ischemic Heart Disease, Silent Myocardial Ischemia, Cardiovascular Diseases
- What is being tested?
- CMR stress perfusion imaging
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,400 participants
- Where
- 1 siteNetherlands
- Study dates
- 27 May 2019to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participation in ROBINSCA or ImaLife study
- CT-CAC ≥300
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Detection of Silent Myocardial Ischemia and Cardiac Dysfunction in Asymptomatic Individuals With Increased Coronary Artery Calcium Scores
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.
Read the 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.
- Being tested
- CMR stress perfusion imaging
- Medical subject headings
- Myocardial Ischemia, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMR stress perfusion imagingDiagnostic test
CMR stress perfusion imaging with feedback of clinically actionable findings to general practitioner and participant
| Study group | Role | What they receive |
|---|---|---|
| Cardiac magnetic resonance imaging | Active comparator | Cardiac magnetic resonance (CMR) stress perfusion imaging with feedback of clinically actionable findings Receives: Diagnostic Test: CMR stress perfusion imaging |
| Control | No intervention | No intervention, following the natural course of coronary atherosclerosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of major adverse cardiac events
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Measured: 1 year
Rate of major adverse cardiac events
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Measured: 2.5 years
Rate of major adverse cardiac events
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Measured: 5 years
Diagnostic yield of CMR stress perfusion imaging
Prevalence and extent of silent myocardial ischemia and cardiac dysfunction
Measured: Baseline
Secondary outcomes (22)
Rate of individual components of primary outcome 1
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Measured: 1 year
Rate of individual components of primary outcome 1
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Measured: 2.5 years
Rate of individual components of primary outcome 1
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Measured: 5 years
All-cause mortality rate
Death from any disease
Measured: 1 year
All-cause mortality rate
Death from any disease
Measured: 2.5 years
All-cause mortality rate
Death from any disease
Measured: 5 years
Rate of invasive cardiovascular procedures
percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) surgery, invasive coronary angiography (ICA) and other invasive cardiovascular procedures
Measured: 1 year
Rate of invasive cardiovascular procedures
percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) surgery, invasive coronary angiography (ICA) and other invasive cardiovascular procedures
Measured: 2.5 years
Rate of invasive cardiovascular procedures
percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) surgery, invasive coronary angiography (ICA) and other invasive cardiovascular procedures
Measured: 5 years
Rate of hospitalization for cardiovascular disease
Hospitalization for cardiovascular disease (e.g. stroke, peripheral vascular disease)
Measured: 1, 2.5, 5 years
Rate of hospitalization for cardiovascular disease
Hospitalization for cardiovascular disease (e.g. stroke, peripheral vascular disease)
Measured: 1 year
Rate of hospitalization for cardiovascular disease
Hospitalization for cardiovascular disease (e.g. stroke, peripheral vascular disease)
Measured: 2.5 years
Rate of non-invasive cardiac imaging procedures
Rate of non-invasive cardiac imaging procedures (e.g., myocardial stress perfusion imaing, echocardiography)
Measured: 5 years
Rate of medical therapy initiation
Initiation of preventive or cardio-active medication (e.g., ACE-inhibiters, statins, calcium antagonists, beta-blockers etc.)
Measured: 1 year
Rate of medical therapy initiation
Initiation of preventive or cardio-active medication (e.g., ACE-inhibiters, statins, calcium antagonists, beta-blockers etc.)
Measured: 2.5 years
Rate of medical therapy initiation
Initiation of preventive or cardio-active medication (e.g., ACE-inhibiters, statins, calcium antagonists, beta-blockers etc.)
Measured: 5 years
Quality of Life as reflected by EQ-5D-5S score
Quality of life as assessed by EQ-5D-5S questionnaire
Measured: 1 year
Quality of Life as reflected by EQ-5D-5S score
Quality of life as assessed by EQ-5D-5S questionnaire
Measured: 2.5 years
Quality of Life as reflected by EQ-5D-5S score
Quality of life as assessed by EQ-5D-5S questionnaire
Measured: 5 years
Quality of Life as reflected by HeartQoL score
Quality of life as assessed by HeartQoL questionnaire
Measured: 1 year
Quality of Life as reflected by HeartQoL score
Quality of life as assessed by HeartQoL questionnaire
Measured: 2.5 years
Quality of Life as reflected by HeartQoL score
Quality of life as assessed by HeartQoL questionnaire
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2020
- Study start27 May 2019
- Primary completionDec 2021 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ischemic Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pim van der Harst
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Pim van der Harst, University Medical Center Groningen
- Investigators
- Pim van der Harst, MD, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04680338
- Sponsor's protocol ID
- NL64860.042.18
- Acronym
- EarlySynergy
- Status last verified
- Apr 2021
- First submitted
- 11 Dec 2020
- Last updated
- 30 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data management plan in progress
Publications
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.
PubMed 31016436Vonder 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.
PubMed 28843465Lenselink C, Ties D, Voordes GHD, Voors AA, de Kleijn DPV, Vliegenthart R, van der Harst P, Lipsic E. Biomarkers in plasma and extracellular vesicles for early detection of asymptomatic ischemic heart disease: a retrospective case-control study. Cardiovasc Diagn Ther. 2026 Aug 31;16(4):62. doi: 10.21037/cdt-2025-1-678. Epub 2026 Jul 30.
PubMed 42719294
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Silent Myocardial Ischemia and Cardiac Dysfunction in Asymptomatic Individuals With Increased Coronary Artery Calcium Scores
- ClinicalTrials.gov ID
- NCT04680338
- Acronym / sponsor ID
- EarlySynergy / NL64860.042.18
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,400 participants (estimated)
- Lead sponsor
- Pim van der HarstUniversity, hospital or other
- Study start
- 27 May 2019 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 22 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cardiac magnetic resonance imaging | Active comparator | Diagnostic Test: CMR stress perfusion imagingCardiac magnetic resonance (CMR) stress perfusion imaging with feedback of clinically actionable findings |
| Control | No intervention | –No intervention, following the natural course of coronary atherosclerosis |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participation in ROBINSCA or ImaLife study
- CT-CAC ≥300
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMR stress perfusion imagingCMR stress perfusion imaging with feedback of clinically actionable findings to general practitioner and participant | Diagnostic test | Cardiac magnetic resonance imaging |
Primary outcome
Rate of major adverse cardiac events
Time frame: 1 year
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Rate of major adverse cardiac events
Time frame: 2.5 years
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Rate of major adverse cardiac events
Time frame: 5 years
Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest
Diagnostic yield of CMR stress perfusion imaging
Time frame: Baseline
Prevalence and extent of silent myocardial ischemia and cardiac dysfunction
22 secondary outcomes
Rate of individual components of primary outcome 1
Time frame: 1 year
Rate of individual components of primary outcome 1
Time frame: 2.5 years
Rate of individual components of primary outcome 1
Time frame: 5 years
All-cause mortality rate
Time frame: 1 year
All-cause mortality rate
Time frame: 2.5 years
All-cause mortality rate
Time frame: 5 years
Rate of invasive cardiovascular procedures
Time frame: 1 year
Rate of invasive cardiovascular procedures
Time frame: 2.5 years
Rate of invasive cardiovascular procedures
Time frame: 5 years
Rate of hospitalization for cardiovascular disease
Time frame: 1, 2.5, 5 years
Rate of hospitalization for cardiovascular disease
Time frame: 1 year
Rate of hospitalization for cardiovascular disease
Time frame: 2.5 years
Rate of non-invasive cardiac imaging procedures
Time frame: 5 years
Rate of medical therapy initiation
Time frame: 1 year
Rate of medical therapy initiation
Time frame: 2.5 years
Rate of medical therapy initiation
Time frame: 5 years
Quality of Life as reflected by EQ-5D-5S score
Time frame: 1 year
Quality of Life as reflected by EQ-5D-5S score
Time frame: 2.5 years
Quality of Life as reflected by EQ-5D-5S score
Time frame: 5 years
Quality of Life as reflected by HeartQoL score
Time frame: 1 year
Quality of Life as reflected by HeartQoL score
Time frame: 2.5 years
Quality of Life as reflected by HeartQoL score
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2021.
- Background: PubMed 31016436Xia 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.
- Background: PubMed 28843465Vonder 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.
- Derived from this study: PubMed 42719294Lenselink C, Ties D, Voordes GHD, Voors AA, de Kleijn DPV, Vliegenthart R, van der Harst P, Lipsic E. Biomarkers in plasma and extracellular vesicles for early detection of asymptomatic ischemic heart disease: a retrospective case-control study. Cardiovasc Diagn Ther. 2026 Aug 31;16(4):62. doi: 10.21037/cdt-2025-1-678. Epub 2026 Jul 30.
- Individual participant dataSharing planned: Yes. Data management plan in progress
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pim van der Harst, MD, PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CMR stress perfusion imaging in people with Ischemic Heart Disease and Silent Myocardial Ischemia, run by Pim van der Harst at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of major adverse cardiac events (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04680338, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2021.