AsymptomaticFINDNCT04388280
Imaging vs. no Testing in Asymptomatic High-risk Diabetic Patients
A study testing Echocardiography and CT angiography in people with Asymptomatic and High Risk, run by Clinical Centre of Serbia at 1 site in Serbia.
Trial summary
The aim of our study was to evaluate 1- and 3-year outcome of alternative imaging strategies in asymptomatic high-risk diabetic patients: functional stress echocardiography combined with coronary flow reserve (CFR) and strain imaging, or computed tomography (CT) angiography with direct visualization of coronary… Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Asymptomatic, High Risk, Diabetes
- What is being tested?
- Echocardiography and CT angiography
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteSerbia
- Study dates
- 28 Jan 2021to 31 Dec 2023
- 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Asymptomatic patients (>30 years) with duration of diabetes ≥10 years without target organ damage plus any other additional risk factor including age, hypertension, dyslipidemia, smoking, and obesity.
Who cannot join
- Patient categorized as very high or moderate risk for CV diseases
- Any symptoms suggestive of angina or heart failure
- Patients with baseline ECG or echo abnormalities
- Patients with known CV disease, or previous myocardial revascularization
- Patients with target organ damage defined as proteinuria, renal impairment defined as eGFR <30 mL/min/1.73 m2, left ventricular hypertrophy, or retinopathy
Trial locations and contacts
1 site in 1 country.
Serbia1 site, 1 recruiting
- Recruiting
Clinical Centre of Serbia
Belgrade, 11000
Branko Beleslin, MD, PhD, +381638328690, branko.beleslin@gmail.com
Nikola Boskovic, MD, +381642708940, belkan87@gmail.com
About this study
Official title: Functional and Anatomic Imaging Versus No Testing in Asymptomatic High-risk Diabetic Patients
The aim of our study was to evaluate 1- and 3-year outcome of alternative imaging strategies in asymptomatic high-risk diabetic patients: functional stress echocardiography combined with coronary flow reserve (CFR) and strain imaging, or computed tomography (CT) angiography with direct visualization of coronary arteries, and no testing at all.
Read the detailed description
A meta-analysis of >100 prospective studies, showed that diabetes mellitus (DM) in general carries a two-fold excess risk of vascular outcomes (coronary artery disease, ischemic stroke, and vascular deaths), independent of other risk factors (1). Although type 2 diabetes mellitus (DM) is far more common than type 1 DM, these results confirm adverse prognosis in both populations, which is particularly severe in the young in general and young onset female individuals with type 1 DM, emphasizing the need for intensive risk-factor management in these groups.
According to new 2019 European Society of Cardiology (ESC) / European Association for the study of diabetes (EASD) guidelines for diabetes, pre-diabetes and cardiovascular diseases (2) individuals with DM and cardiovascular diseases (CVD), or DM with target organ damage, such as proteinuria or renal failure (estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2), are at very high risk (10-year risk of CVD death >10%). Patients with DM with three or more major risk factors, or with a DM duration of >20 years, are also at very high risk. Type 1 DM at the age of 40 years with early onset (i.e. 1-10 years of age) and particularly female are associated with very high CV risk (2). Most others with DM are high risk, 10 year risk of cardiovascular diseases death (CVD) 5-10%, with the exception of young patients (aged <35 years) with type 1 DM of short duration (<10 years), and patients with type 2 DM aged <50 years with a DM duration of <10 years and without major risk factors, who are at moderate risk.
Screening for asymptomatic CAD in patients with DM remains controversial. According to current guidelines only resting ECG is recommended in patients with suspected CVD, whereas computed tomography (CT) angiography or functional imaging (radionuclide myocardial perfusion imaging, magnetic resonance imaging, or physical or pharmacological stress echocardiography) may be considered (class IIb) in asymptomatic patients with DM for screening of coronary artery disease (CAD) (2). With CT, non-invasive estimation of the atherosclerotic burden (based on the coronary artery calcium score) and identification of atherosclerotic plaques causing significant coronary stenosis (CT angiography) can be performed. Patients with DM have a higher prevalence of coronary artery calcification compared with age- and sex-matched subjects without DM (3). While a coronary artery calcium (CAC) score of 0 is associated with favorable prognosis in asymptomatic subjects with DM, each increment in CAC score (from 1 - 99 to 100 - 399 and ≥400) is associated with a 25 - 33% higher relative risk of mortality (3). Importantly, CAC is not always associated with ischemia. Therefore, coronary artery calcium score may be considered as risk modifier in CV assessment in asymptomatic patients with moderate risk (2).
Stress testing with myocardial perfusion imaging or stress echocardiography allows the detection of myocardial ischemia, particularly silent form which is more prevalent in patients with DM as demonstrated by observational studies (22%) (4-6). Randomized trials evaluating the impact of routine screening for CAD in asymptomatic DM and no history of CAD have shown no differences in cardiac death and unstable angina at follow-up in those who underwent stress testing, or CT angiography (4,6,7). A meta-analysis of five randomized studies with 3299 asymptomatic subjects with DM showed that non-invasive imaging for CAD did not significantly reduce event rates of non-fatal myocardial infarction (MI) (relative risk 0.65; P=0.062) and hospitalization for heart failure (HF) (relative risk 0.61;P=0.1) (8).Observed low event rates in these studies and the disparities in patient population and the management of screening results (different imaging techniques, invasive coronary angiography and revascularization were not performed systematically) may explain the lack of benefit of the screening strategy. Accordingly, routine screening of CAD in asymptomatic DM is not recommended (2, 8) However, stress testing or CT angiography may be indicated in very high-risk asymptomatic individuals (with peripheral arterial disease (PAD), a high CAC score, proteinuria, or renal failure) (9).
The addition of circulating biomarkers for CV risk assessment has limited clinical value (10). In patients with DM without known CVD, measurement of C-reactive protein or fibrinogen (inflammatory markers) provides minor incremental value to current risk assessment. The addition of hs troponin (Tn) T to conventional risk factors has not shown incremental discriminative power in this group (11). In individuals with type 1 DM, elevated high sensitive troponin T (hsTnT) was an independent predictor of renal decline and CV events (12). The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-pro BNP) in an unselected cohort of people with DM (including known CVD) showed that patients with low levels of NT-pro BNP (<125 pg/mL) have an excellent short-term prognosis (13).
With emerging role of CT angiography in diagnosis of CAD according to the last 2019 ESC guidelines on Chronic coronary syndrome (14), as well as advanced functional imaging techniques, there is an obvious gap in evidence on prognostic value of both functional and angiographic advanced imaging techniques in patients with diabetes, particularly high risk subgroup.
The investigators hypothesized that a strategy using either functional evaluation with advanced stress echocardiography using wall motion abnormalities, coronary flow reserve and strain, or CT angiography visualization will lead to better outcome than no testing at all in asymptomatic high risk diabetic patients.
- Conditions
- Asymptomatic, High Risk, Diabetes
- Being tested
- Echocardiography, CT angiography
- Keywords
- Imaging, MACE, High risk, Diabetes mellitus
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EchocardiographyDiagnostic test
Also called Coronary flow reserve (CFR), Wall motion abnormalities (WMA), Strain
Functional assessment of coronary artery disease
CT angiographyDiagnostic test
Anatomical assessment of coronary artery disease
| Study group | Role | What they receive |
|---|---|---|
| Imaging | Other | Echocardiography combined with coronary flow reserve (CFR) and strain imaging, or computed tomography (CT) angiography with direct visualization of coronary arteries. Receives: Diagnostic Test: Echocardiography; Diagnostic Test: CT angiography |
| Observation | No intervention | No imaging for the estimation of coronary artery disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major adverse cardiovascular events (MACE)
Number of participants with all-cause mortality, non-fatal MI and unstable angina
Measured: 1 to 3 years
Secondary outcomes (7)
Individual MACE
Number of participants with all-cause mortality, cardiovascular mortality, non-fatal MI, revascularization (PCI or CABG), acute coronary syndrome, appearance and/or hospitalization for angina, and stroke
Measured: 1 to 3 years
Testing-driven invasive angiography and revascularization
Number of participants undergoing invasive coronary angiography (ICA) and revascularization and rate of MACE due to invasive angiogaphy and revascularization
Measured: 1 to 3 years
Prognostic role of iFR/FFR imaging in patients referred to angiography
Number of participants with MACE and rate of MACE in patients undergoing instantaneous wave-free ratio (iFR) and fractional flow reserve in (FFR)
Measured: 1 to 3 years
Safety and outcome of revascularization in testing arms
Number of participants with MACE and rate of MACE due to revascularization
Measured: 1 to 3 years
The role of biomarkers in high risk DM patients on their outcome (MACE)
Value of C-reactive protein (CRP), NT-pro BNP, and hsTnT in all participants
Measured: 1 to 3 years
The impact of antidiabetic therapy and sugar control in high risk DM patients on their outcome
Number of participants with MACE and rate of MACE in high risk DM participants regarding antidiabetic therapy
Measured: 1 to 3 years
Differences in the outcome between functional and angiographic imaging in imaging arm
Number of participants with MACE and rate of MACE regarding the initial imaging modality
Measured: 1 to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start28 Jan 2021
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for AsymptomaticStudies 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
- Model description
- multi-center prospective, randomized, open label, parallel group comparison of 2 diagnostic strategies
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Centre of Serbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Branko Beleslin, Clinical Centre of Serbia
- Investigators
- Branko Beleslin, MD, PhD, Principal investigator, Clinical Centre of SerbiaNebojsa Lalic, MD, PhD, Principal investigator, Clinical Centre of SerbiaMilos Zarkovic, MD, PhD, Principal investigator, Clinical Centre of Serbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04388280
- Sponsor's protocol ID
- 485/20
- Acronym
- FIND
- Status last verified
- Aug 2021
- First submitted
- 11 May 2020
- Last updated
- 18 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Emerging Risk Factors Collaboration; Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010 Jun 26;375(9733):2215-22. doi: 10.1016/S0140-6736(10)60484-9.
PubMed 20609967Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV, Johansson I, Juni P, Lettino M, Marx N, Mellbin LG, Ostgren CJ, Rocca B, Roffi M, Sattar N, Seferovic PM, Sousa-Uva M, Valensi P, Wheeler DC; ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020 Jan 7;41(2):255-323. doi: 10.1093/eurheartj/ehz486. No abstract available.
PubMed 31497854Valenti V, Hartaigh BO, Cho I, Schulman-Marcus J, Gransar H, Heo R, Truong QA, Shaw LJ, Knapper J, Kelkar AA, Sciarretta S, Chang HJ, Callister TQ, Min JK. Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality: A 15-Year Follow-Up Study of 9715 Patients. Circ Cardiovasc Imaging. 2016 Feb;9(2):e003528. doi: 10.1161/CIRCIMAGING.115.003528.
PubMed 26848062Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner RE, Iskandrian AE; Detection of Ischemia in Asymptomatic Diabetics Investigators. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care. 2004 Aug;27(8):1954-61. doi: 10.2337/diacare.27.8.1954.
PubMed 15277423Zellweger MJ, Maraun M, Osterhues HH, Keller U, Muller-Brand J, Jeger R, Pfister O, Burkard T, Eckstein F, von Felten S, Osswald S, Pfisterer M. Progression to overt or silent CAD in asymptomatic patients with diabetes mellitus at high coronary risk: main findings of the prospective multicenter BARDOT trial with a pilot randomized treatment substudy. JACC Cardiovasc Imaging. 2014 Oct;7(10):1001-10. doi: 10.1016/j.jcmg.2014.07.010. Epub 2014 Sep 17.
PubMed 25240454Lievre MM, Moulin P, Thivolet C, Rodier M, Rigalleau V, Penfornis A, Pradignac A, Ovize M; DYNAMIT investigators. Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening. Trials. 2011 Jan 26;12:23. doi: 10.1186/1745-6215-12-23.
PubMed 21269454Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE; DIAD Investigators. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009 Apr 15;301(15):1547-55. doi: 10.1001/jama.2009.476.
PubMed 19366774Clerc OF, Fuchs TA, Stehli J, Benz DC, Grani C, Messerli M, Giannopoulos AA, Buechel RR, Luscher TF, Pazhenkottil AP, Kaufmann PA, Gaemperli O. Non-invasive screening for coronary artery disease in asymptomatic diabetic patients: a systematic review and meta-analysis of randomised controlled trials. Eur Heart J Cardiovasc Imaging. 2018 Aug 1;19(8):838-846. doi: 10.1093/ehjci/jey014.
PubMed 29452348Authors/Task Force Members; Ryden L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, Deaton C, Escaned J, Hammes HP, Huikuri H, Marre M, Marx N, Mellbin L, Ostergren J, Patrono C, Seferovic P, Uva MS, Taskinen MR, Tendera M, Tuomilehto J, Valensi P, Zamorano JL; ESC Committee for Practice Guidelines (CPG); Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers; De Backer G, Sirnes PA, Ezquerra EA, Avogaro A, Badimon L, Baranova E, Baumgartner H, Betteridge J, Ceriello A, Fagard R, Funck-Brentano C, Gulba DC, Hasdai D, Hoes AW, Kjekshus JK, Knuuti J, Kolh P, Lev E, Mueller C, Neyses L, Nilsson PM, Perk J, Ponikowski P, Reiner Z, Sattar N, Schachinger V, Scheen A, Schirmer H, Stromberg A, Sudzhaeva S, Tamargo JL, Viigimaa M, Vlachopoulos C, Xuereb RG. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013 Oct;34(39):3035-87. doi: 10.1093/eurheartj/eht108. Epub 2013 Aug 30. No abstract available.
PubMed 23996285Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. No abstract available.
PubMed 27222591Price AH, Weir CJ, Welsh P, McLachlan S, Strachan MWJ, Sattar N, Price JF. Comparison of non-traditional biomarkers, and combinations of biomarkers, for vascular risk prediction in people with type 2 diabetes: The Edinburgh Type 2 Diabetes Study. Atherosclerosis. 2017 Sep;264:67-73. doi: 10.1016/j.atherosclerosis.2017.07.009. Epub 2017 Jul 12.
PubMed 28777936Galsgaard J, Persson F, Hansen TW, Jorsal A, Tarnow L, Parving HH, Rossing P. Plasma high-sensitivity troponin T predicts end-stage renal disease and cardiovascular and all-cause mortality in patients with type 1 diabetes and diabetic nephropathy. Kidney Int. 2017 Nov;92(5):1242-1248. doi: 10.1016/j.kint.2017.04.018. Epub 2017 Jul 14.
PubMed 28712855Huelsmann M, Neuhold S, Strunk G, Moertl D, Berger R, Prager R, Abrahamian H, Riedl M, Pacher R, Luger A, Clodi M. NT-proBNP has a high negative predictive value to rule-out short-term cardiovascular events in patients with diabetes mellitus. Eur Heart J. 2008 Sep;29(18):2259-64. doi: 10.1093/eurheartj/ehn334. Epub 2008 Jul 23.
PubMed 18650200Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. No abstract available.
PubMed 31504439
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional and Anatomic Imaging Versus No Testing in Asymptomatic High-risk Diabetic Patients
- ClinicalTrials.gov ID
- NCT04388280
- Acronym / sponsor ID
- FIND / 485/20
- Conditions
- Asymptomatic, High Risk, Diabetes
- Keywords
- Imaging, MACE, High risk, Diabetes mellitus
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Clinical Centre of SerbiaUniversity, hospital or other
- Study start
- 28 Jan 2021 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 14 May 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.
The aim of our study was to evaluate 1- and 3-year outcome of alternative imaging strategies in asymptomatic high-risk diabetic patients: functional stress echocardiography combined with coronary flow reserve (CFR) and strain imaging, or computed tomography (CT) angiography with direct visualization of coronary arteries, and no testing at all.
Detailed description
A meta-analysis of >100 prospective studies, showed that diabetes mellitus (DM) in general carries a two-fold excess risk of vascular outcomes (coronary artery disease, ischemic stroke, and vascular deaths), independent of other risk factors (1). Although type 2 diabetes mellitus (DM) is far more common than type 1 DM, these results confirm adverse prognosis in both populations, which is particularly severe in the young in general and young onset female individuals with type 1 DM, emphasizing the need for intensive risk-factor management in these groups.
According to new 2019 European Society of Cardiology (ESC) / European Association for the study of diabetes (EASD) guidelines for diabetes, pre-diabetes and cardiovascular diseases (2) individuals with DM and cardiovascular diseases (CVD), or DM with target organ damage, such as proteinuria or renal failure (estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2), are at very high risk (10-year risk of CVD death >10%). Patients with DM with three or more major risk factors, or with a DM duration of >20 years, are also at very high risk. Type 1 DM at the age of 40 years with early onset (i.e. 1-10 years of age) and particularly female are associated with very high CV risk (2). Most others with DM are high risk, 10 year risk of cardiovascular diseases death (CVD) 5-10%, with the exception of young patients (aged <35 years) with type 1 DM of short duration (<10 years), and patients with type 2 DM aged <50 years with a DM duration of <10 years and without major risk factors, who are at moderate risk.
Screening for asymptomatic CAD in patients with DM remains controversial. According to current guidelines only resting ECG is recommended in patients with suspected CVD, whereas computed tomography (CT) angiography or functional imaging (radionuclide myocardial perfusion imaging, magnetic resonance imaging, or physical or pharmacological stress echocardiography) may be considered (class IIb) in asymptomatic patients with DM for screening of coronary artery disease (CAD) (2). With CT, non-invasive estimation of the atherosclerotic burden (based on the coronary artery calcium score) and identification of atherosclerotic plaques causing significant coronary stenosis (CT angiography) can be performed. Patients with DM have a higher prevalence of coronary artery calcification compared with age- and sex-matched subjects without DM (3). While a coronary artery calcium (CAC) score of 0 is associated with favorable prognosis in asymptomatic subjects with DM, each increment in CAC score (from 1 - 99 to 100 - 399 and ≥400) is associated with a 25 - 33% higher relative risk of mortality (3). Importantly, CAC is not always associated with ischemia. Therefore, coronary artery calcium score may be considered as risk modifier in CV assessment in asymptomatic patients with moderate risk (2).
Stress testing with myocardial perfusion imaging or stress echocardiography allows the detection of myocardial ischemia, particularly silent form which is more prevalent in patients with DM as demonstrated by observational studies (22%) (4-6). Randomized trials evaluating the impact of routine screening for CAD in asymptomatic DM and no history of CAD have shown no differences in cardiac death and unstable angina at follow-up in those who underwent stress testing, or CT angiography (4,6,7). A meta-analysis of five randomized studies with 3299 asymptomatic subjects with DM showed that non-invasive imaging for CAD did not significantly reduce event rates of non-fatal myocardial infarction (MI) (relative risk 0.65; P=0.062) and hospitalization for heart failure (HF) (relative risk 0.61;P=0.1) (8).Observed low event rates in these studies and the disparities in patient population and the management of screening results (different imaging techniques, invasive coronary angiography and revascularization were not performed systematically) may explain the lack of benefit of the screening strategy. Accordingly, routine screening of CAD in asymptomatic DM is not recommended (2, 8) However, stress testing or CT angiography may be indicated in very high-risk asymptomatic individuals (with peripheral arterial disease (PAD), a high CAC score, proteinuria, or renal failure) (9).
The addition of circulating biomarkers for CV risk assessment has limited clinical value (10). In patients with DM without known CVD, measurement of C-reactive protein or fibrinogen (inflammatory markers) provides minor incremental value to current risk assessment. The addition of hs troponin (Tn) T to conventional risk factors has not shown incremental discriminative power in this group (11). In individuals with type 1 DM, elevated high sensitive troponin T (hsTnT) was an independent predictor of renal decline and CV events (12). The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-pro BNP) in an unselected cohort of people with DM (including known CVD) showed that patients with low levels of NT-pro BNP (<125 pg/mL) have an excellent short-term prognosis (13).
With emerging role of CT angiography in diagnosis of CAD according to the last 2019 ESC guidelines on Chronic coronary syndrome (14), as well as advanced functional imaging techniques, there is an obvious gap in evidence on prognostic value of both functional and angiographic advanced imaging techniques in patients with diabetes, particularly high risk subgroup.
The investigators hypothesized that a strategy using either functional evaluation with advanced stress echocardiography using wall motion abnormalities, coronary flow reserve and strain, or CT angiography visualization will lead to better outcome than no testing at all in asymptomatic high risk diabetic patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- multi-center prospective, randomized, open label, parallel group comparison of 2 diagnostic strategies
| Arm | Type | Receives |
|---|---|---|
| Imaging | Other | Diagnostic Test: Echocardiography, Diagnostic Test: CT angiographyEchocardiography combined with coronary flow reserve (CFR) and strain imaging, or computed tomography (CT) angiography with direct visualization of coronary arteries. |
| Observation | No intervention | –No imaging for the estimation of coronary artery disease |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Asymptomatic patients (>30 years) with duration of diabetes ≥10 years without target organ damage plus any other additional risk factor including age, hypertension, dyslipidemia, smoking, and obesity.
Key exclusion criteria (5 listed)
- Patient categorized as very high or moderate risk for CV diseases
- Any symptoms suggestive of angina or heart failure
- Patients with baseline ECG or echo abnormalities
- Patients with known CV disease, or previous myocardial revascularization
- Patients with target organ damage defined as proteinuria, renal impairment defined as eGFR <30 mL/min/1.73 m2, left ventricular hypertrophy, or retinopathy
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 |
|---|---|---|
| EchocardiographyAlso: Coronary flow reserve (CFR), Wall motion abnormalities (WMA), StrainFunctional assessment of coronary artery disease | Diagnostic test | Imaging |
| CT angiographyAnatomical assessment of coronary artery disease | Diagnostic test | Imaging |
Primary outcome
Major adverse cardiovascular events (MACE)
Time frame: 1 to 3 years
Number of participants with all-cause mortality, non-fatal MI and unstable angina
7 secondary outcomes
Individual MACE
Time frame: 1 to 3 years
Testing-driven invasive angiography and revascularization
Time frame: 1 to 3 years
Prognostic role of iFR/FFR imaging in patients referred to angiography
Time frame: 1 to 3 years
Safety and outcome of revascularization in testing arms
Time frame: 1 to 3 years
The role of biomarkers in high risk DM patients on their outcome (MACE)
Time frame: 1 to 3 years
The impact of antidiabetic therapy and sugar control in high risk DM patients on their outcome
Time frame: 1 to 3 years
Differences in the outcome between functional and angiographic imaging in imaging arm
Time frame: 1 to 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2021.
- Results publication: PubMed 20609967Emerging Risk Factors Collaboration; Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010 Jun 26;375(9733):2215-22. doi: 10.1016/S0140-6736(10)60484-9.
- Results publication: PubMed 31497854Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV, Johansson I, Juni P, Lettino M, Marx N, Mellbin LG, Ostgren CJ, Rocca B, Roffi M, Sattar N, Seferovic PM, Sousa-Uva M, Valensi P, Wheeler DC; ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020 Jan 7;41(2):255-323. doi: 10.1093/eurheartj/ehz486. No abstract available.
- Results publication: PubMed 26848062Valenti V, Hartaigh BO, Cho I, Schulman-Marcus J, Gransar H, Heo R, Truong QA, Shaw LJ, Knapper J, Kelkar AA, Sciarretta S, Chang HJ, Callister TQ, Min JK. Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality: A 15-Year Follow-Up Study of 9715 Patients. Circ Cardiovasc Imaging. 2016 Feb;9(2):e003528. doi: 10.1161/CIRCIMAGING.115.003528.
- Results publication: PubMed 15277423Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner RE, Iskandrian AE; Detection of Ischemia in Asymptomatic Diabetics Investigators. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care. 2004 Aug;27(8):1954-61. doi: 10.2337/diacare.27.8.1954.
- Results publication: PubMed 25240454Zellweger MJ, Maraun M, Osterhues HH, Keller U, Muller-Brand J, Jeger R, Pfister O, Burkard T, Eckstein F, von Felten S, Osswald S, Pfisterer M. Progression to overt or silent CAD in asymptomatic patients with diabetes mellitus at high coronary risk: main findings of the prospective multicenter BARDOT trial with a pilot randomized treatment substudy. JACC Cardiovasc Imaging. 2014 Oct;7(10):1001-10. doi: 10.1016/j.jcmg.2014.07.010. Epub 2014 Sep 17.
- Results publication: PubMed 21269454Lievre MM, Moulin P, Thivolet C, Rodier M, Rigalleau V, Penfornis A, Pradignac A, Ovize M; DYNAMIT investigators. Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening. Trials. 2011 Jan 26;12:23. doi: 10.1186/1745-6215-12-23.
- Results publication: PubMed 19366774Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE; DIAD Investigators. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009 Apr 15;301(15):1547-55. doi: 10.1001/jama.2009.476.
- Results publication: PubMed 29452348Clerc OF, Fuchs TA, Stehli J, Benz DC, Grani C, Messerli M, Giannopoulos AA, Buechel RR, Luscher TF, Pazhenkottil AP, Kaufmann PA, Gaemperli O. Non-invasive screening for coronary artery disease in asymptomatic diabetic patients: a systematic review and meta-analysis of randomised controlled trials. Eur Heart J Cardiovasc Imaging. 2018 Aug 1;19(8):838-846. doi: 10.1093/ehjci/jey014.
- Results publication: PubMed 23996285Authors/Task Force Members; Ryden L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, Deaton C, Escaned J, Hammes HP, Huikuri H, Marre M, Marx N, Mellbin L, Ostergren J, Patrono C, Seferovic P, Uva MS, Taskinen MR, Tendera M, Tuomilehto J, Valensi P, Zamorano JL; ESC Committee for Practice Guidelines (CPG); Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers; De Backer G, Sirnes PA, Ezquerra EA, Avogaro A, Badimon L, Baranova E, Baumgartner H, Betteridge J, Ceriello A, Fagard R, Funck-Brentano C, Gulba DC, Hasdai D, Hoes AW, Kjekshus JK, Knuuti J, Kolh P, Lev E, Mueller C, Neyses L, Nilsson PM, Perk J, Ponikowski P, Reiner Z, Sattar N, Schachinger V, Scheen A, Schirmer H, Stromberg A, Sudzhaeva S, Tamargo JL, Viigimaa M, Vlachopoulos C, Xuereb RG. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013 Oct;34(39):3035-87. doi: 10.1093/eurheartj/eht108. Epub 2013 Aug 30. No abstract available.
- Results publication: PubMed 27222591Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. No abstract available.
- Results publication: PubMed 28777936Price AH, Weir CJ, Welsh P, McLachlan S, Strachan MWJ, Sattar N, Price JF. Comparison of non-traditional biomarkers, and combinations of biomarkers, for vascular risk prediction in people with type 2 diabetes: The Edinburgh Type 2 Diabetes Study. Atherosclerosis. 2017 Sep;264:67-73. doi: 10.1016/j.atherosclerosis.2017.07.009. Epub 2017 Jul 12.
- Results publication: PubMed 28712855Galsgaard J, Persson F, Hansen TW, Jorsal A, Tarnow L, Parving HH, Rossing P. Plasma high-sensitivity troponin T predicts end-stage renal disease and cardiovascular and all-cause mortality in patients with type 1 diabetes and diabetic nephropathy. Kidney Int. 2017 Nov;92(5):1242-1248. doi: 10.1016/j.kint.2017.04.018. Epub 2017 Jul 14.
- Chow S, Shao J, Wand H. Sample size calculations in clinical research. 2nd edition. 2008.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Branko Beleslin, MD, PhD principal investigator
Clinical Centre of Serbia
Nebojsa Lalic, MD, PhD principal investigator
Clinical Centre of Serbia
Milos Zarkovic, MD, PhD principal investigator
Clinical Centre of Serbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Echocardiography and CT angiography in people with Asymptomatic and High Risk, run by Clinical Centre of Serbia at 1 site in Serbia.
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 1 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 18 Aug 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 Serbia. 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?
Contact Branko Beleslin, MD, PhD (+381638328690, branko.beleslin@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major adverse cardiovascular events (MACE) (time frame: 1 to 3 years). 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 NCT04388280, which also lists 14 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 18 Aug 2021.