Imaging vs. no Testing in Asymptomatic High-risk Diabetic Patients (FIND)

August 11, 2021 updated by: Branko Beleslin, Clinical Centre of Serbia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • Clinical Centre of Serbia
        • Contact:
        • Contact:
        • Principal Investigator:
          • Branko Beleslin, MD, PhD
        • Sub-Investigator:
          • Ana Djordjevic-Dikic, MD, PhD
        • Sub-Investigator:
          • Vojislav Giga, MD, PhD
        • Sub-Investigator:
          • Nikola Boskovic, MD
        • Sub-Investigator:
          • Srdjan Dedic, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Imaging
Echocardiography combined with coronary flow reserve (CFR) and strain imaging, or computed tomography (CT) angiography with direct visualization of coronary arteries.
Diagnostic test: Echocardiography
Functional assessment of coronary artery disease
Other Names:
  • Strain
  • Coronary flow reserve (CFR)
  • Wall motion abnormalities (WMA)
Diagnostic test: CT angiography
Anatomical assessment of coronary artery disease
NO_INTERVENTION: Observation
No imaging for the estimation of coronary artery disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major adverse cardiovascular events (MACE)
Time Frame: 1 to 3 years
Number of participants with all-cause mortality, non-fatal MI and unstable angina
1 to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Individual MACE
Time Frame: 1 to 3 years
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
1 to 3 years
Testing-driven invasive angiography and revascularization
Time Frame: 1 to 3 years
Number of participants undergoing invasive coronary angiography (ICA) and revascularization and rate of MACE due to invasive angiogaphy and revascularization
1 to 3 years
Prognostic role of iFR/FFR imaging in patients referred to angiography
Time Frame: 1 to 3 years
Number of participants with MACE and rate of MACE in patients undergoing instantaneous wave-free ratio (iFR) and fractional flow reserve in (FFR)
1 to 3 years
Safety and outcome of revascularization in testing arms
Time Frame: 1 to 3 years
Number of participants with MACE and rate of MACE due to revascularization
1 to 3 years
The role of biomarkers in high risk DM patients on their outcome (MACE)
Time Frame: 1 to 3 years
Value of C-reactive protein (CRP), NT-pro BNP, and hsTnT in all participants
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
Number of participants with MACE and rate of MACE in high risk DM participants regarding antidiabetic therapy
1 to 3 years
Differences in the outcome between functional and angiographic imaging in imaging arm
Time Frame: 1 to 3 years
Number of participants with MACE and rate of MACE regarding the initial imaging modality
1 to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinical Centre of Serbia

Investigators

  • Principal Investigator: Nebojsa Lalic, MD, PhD, Clinical Centre of Serbia
  • Principal Investigator: Milos Zarkovic, MD, PhD, Clinical Centre of Serbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 28, 2021

Primary Completion (ANTICIPATED)

December 31, 2023

Study Completion (ANTICIPATED)

December 31, 2023

Study Registration Dates

First Submitted

May 11, 2020

First Submitted That Met QC Criteria

May 11, 2020

First Posted (ACTUAL)

May 14, 2020

Study Record Updates

Last Update Posted (ACTUAL)

August 18, 2021

Last Update Submitted That Met QC Criteria

August 11, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 485/20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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