Clinical Trial Design
Multicenter Evaluation of Coronary Dual-Source CT Angiography in Patients with Intermediate Risk of Coronary Artery Stenoses (MEDIC): Study design and rationale

https://doi.org/10.1016/j.jcct.2014.04.006Get rights and content

Abstract

Background

The diagnostic performance of multidetector row CT to detect coronary artery stenosis has been evaluated in numerous single-center studies, with only limited data from large cohorts with low-to-intermediate likelihood of coronary disease and in multicenter trials. The Multicenter Evaluation of Coronary Dual-Source CT Angiography in Patients with Intermediate Risk of Coronary Artery Stenoses (MEDIC) trial determines the accuracy of dual-source CT (DSCT) to identify persons with at least 1 coronary artery stenosis among patients with low-to-intermediate pretest likelihood of disease.

Methods

The MEDIC trial was designed as a prospective, multicenter, international trial to evaluate the diagnostic performance of DSCT for the detection of coronary artery stenosis compared with invasive coronary angiography. The study includes 8 sites in Germany, India, Mexico, the United States, and Denmark. The study population comprises patients referred for a diagnostic coronary angiogram because of suspected coronary artery disease with an intermediate pretest likelihood as determined by sex, age, and symptoms. All evaluations are performed by blinded core laboratory readers.

Results

The primary outcome of the MEDIC trial is the accuracy of DSCT to identify the presence of coronary artery stenoses with a luminal diameter narrowing of 50% or more on a per-vessel basis. Secondary outcome parameters include per-patient and per-segment diagnostic accuracy for 50% stenoses and accuracy to identify stenoses of 70% or more. Furthermore, secondary outcome parameters include the influence of heart rate, Agatston score, body weight, body mass index, image quality, and diagnostic confidence on the accuracy to detect coronary artery stenoses >50% on a per-vessel basis.

Conclusion

The results of the MEDIC trial will assess the clinical utility of coronary CT angiography in the evaluation of patients with intermediate pretest likelihood of coronary artery disease.

Introduction

Multidetector row CT (MDCT) allows visualization of the coronary arteries and detection of coronary artery stenoses. Two meta-analyses of trials performed by 64-slice CT reported sensitivities for detection of coronary artery stenoses in patients referred for a first diagnostic coronary angiogram to range from 73% to 99%, with specificities between 93% and 97%.1, 2 Although numerous single-center trials have evaluated the performance of 64-slice coronary CT angiography (CTA), so far only 3 multicenter trials with cohort sizes from 230 to 360 patients have been published in peer-reviewed journals.3, 4, 5

Dual-source CT (DSCT) allows imaging of the coronary arteries with better temporal resolution compared with 64-slice CT and may therefore be better suited to identify coronary artery stenoses in patients with elevated heart rates. In smaller trials performed without systematic use of β-blockers, sensitivities of 90% to 96% and specificities of 92% to 98% were reported for the detection of coronary artery stenoses on a per-segment level.6, 7, 8, 9, 10 The maximum number of patients included in these trials was 170, and no large trial that assesses the accuracy of DSCT for the detection of coronary artery stenoses has so far been performed.

According to an American Heart Association scientific statement, the use of coronary CTA is most likely considered clinically beneficial in patients who are at intermediate risk for having coronary artery stenoses: Especially in the context of ruling out stenosis in patients with low to intermediate pretest likelihood of disease, CT coronary angiography may develop into a clinically useful tool. CT coronary angiography is reasonable for the assessment of obstructive disease in symptomatic patients (Class IIa, Level of Evidence: B, p. 1763).11 Another recent statement on noninvasive imaging of the coronary artery reads as follows: The potential benefit of noninvasive coronary angiography is likely to be greatest and is reasonable for symptomatic patients who are at intermediate risk for coronary artery disease after initial risk stratification, including patients with equivocal stress-test results (Class IIa, level of evidence B, p. 598). Diagnostic accuracy favors coronary CTA over MRA [magnetic resonance angiography] for these patients (Class I, level of evidence B, p. 598).12

A sufficiently large clinical trial is therefore needed to confirm the diagnostic accuracy of DSCT coronary angiography in a multicenter setting and to confirm the clinical utility of coronary CTA, specifically in patients with intermediate pretest likelihood of coronary artery stenosis.

Section snippets

Overall study design and population

The Multicenter Evaluation of Coronary Dual-Source CT Angiography in Patients with Intermediate Risk of Coronary Artery Stenoses (MEDIC) trial is a prospective, multicenter, international trial to evaluate the diagnostic performance of DSCT for the detection of coronary artery stenoses. The study includes 8 sites in Germany, India, Mexico, the United States, and Denmark (Table 1). All sites participating in the trial are academic medical centers apart from the CARE Hospital in India. Patient

Results

The aim of the MEDIC trial is to identify the accuracy of DSCT to detect coronary artery stenosis (diameter reduction >50% and >70% on a per-segment, per-vessel, and per-patient level) compared with invasive coronary angiography as the reference standard and the influence of relevant factors such as body weight, heart rate, and coronary calcifications on accuracy measures. All outcome measures are listed in Table 6.

Discussion

The use of coronary CTA to detect or exclude coronary artery stenoses in patients with suspected coronary disease has been increasing over the past years and is currently part of the clinical workup in specific patient populations. The diagnostic accuracy of coronary CTA to rule out or detect coronary artery disease has been reported in numerous single center trials that used different CT scanner technologies.1, 2 So far, only 3 trials have assessed the performance of 64-slice CT in a

Conclusion

The results of the MEDIC trial aim to deliver information about the diagnostic accuracy and performance of DSCT for detection of significant coronary stenosis in patients with intermediate pretest likelihood of coronary artery disease. The exclusion and inclusion criteria were designed to identify a clinically relevant patient cohort with suspected coronary artery disease. The multicenter and international nature of the study affords for broad generalization of the study results.

References (17)

There are more references available in the full text version of this article.

Cited by (11)

  • Gradient-based enhancement of tubular structures in medical images

    2015, Medical Image Analysis
    Citation Excerpt :

    Imaging and analyzing these structures is important for diagnostic purposes. As an example, computer tomography angiography (CTA) is now a standard clinical tool for diagnosing coronary artery diseases (Marwan et al., 2014; Weustink and de Feyter, 2011) and pulmonary embolism (Hogg et al., 2006; Mos et al., 2009). Magnetic resonance angiography (MRA) is used clinically for imaging the cerebral vessels (Parker et al., 1998) as well as the renal and peripheral arteries (Dong et al., 1999; Prince et al., 1999).

  • Cardiac computed tomography in current cardiology guidelines

    2015, Journal of Cardiovascular Computed Tomography
    Citation Excerpt :

    Most recently, the 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation29 recommend coronary CTA as an alternative to invasive angiography to exclude ACS in patients with low to intermediate likelihood of CAD and inconclusive troponin and ECG (Class of Recommendation IIa; Level of Evidence A). Most of the data regarding the role of coronary CTA in ruling out coronary artery disease (CAD) has been obtained in patients with stable chest pain.13, 30 More recently, multinational large-scale registries and a large-scale randomized clinical trial31 have established the prognostic value and clinical effectiveness of coronary CTA compared to other non-invasive tests for detection of CAD.12, 32

  • Finding the gatekeeper to the cardiac catheterization laboratory: Coronary CT angiography or stress testing?

    2015, Journal of the American College of Cardiology
    Citation Excerpt :

    CCTA has a demonstrated 94% to 99% sensitivity and 64% to 83% specificity across a range of disease prevalence and inclusive of patients with both acute and stable CP (Figure 1). The 97% to 99% negative predictive value (NPV) of CCTA to exclude obstructive anatomic stenosis (18–20) means that a CT-based approach can effectively rule out anatomic CAD. Whereas stress testing is very effective for predicting risk, it is unable to exclude CAD, including severe CAD.

View all citing articles on Scopus

Conflict of interest: Stephan Achenbach: Research Grants, Siemens/Bayer/Abbott Vascular. Mohamed Marwan: Speaker honoraria for Edwards and Siemens. Suhny Abbara: Royalties: Elsevier, Amirsys, Consulting: Radiology Consulting Group (FDA trial reads), Research Funding: NIH. Jörg Hausleiter: Speaker honoraria for Abbott Vascular and Edwards.

View full text