Clinical trial NCT02959099: Incident COronary EveNts Identified by Computed Tomography
Official title: Incident COronary EveNts Identified by Computed Tomography
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atherosclerosis
Keywords: Acute coronary syndrome (ACS)
Atherosclerotic plaque morphology
Coronary Computed Tomographic Angiography (CCTA)
Gender disparities
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2016-11-08
Enrollment: 476
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects were recruited from 13 international sites in Asia, Europe and North America, with central adjudication of clinical outcomes and core-laboratory measurement of CCTA-based plaque characteristics.

Subjects recruited in ICONIC represent individuals suspected of having CAD, meeting the inclusion criteria, and undergoing coronary luminal evaluation using ≥ 64-detector row CCTA. Subjects with established CAD were excluded from the trial. The two arms of the study were patients with baseline CCTA and subsequent occurrence of an ACS event (cases) and patients with baseline CCTA and no subsequent ACS event (controls).

Brief summary: The Incident COronary EveNts Identified by Coronary Tomography (ICONIC) trial is a nested, case-control study derived from the dynamic CONFIRM registry, and is based on propensity scoring methods to match subjects with (cases) or without (controls) acute coronary syndrome (ACS). Our primary objective is to determine CCTA-based atherosclerotic plaque characteristics that would help elucidate precursors of incident ACS, with the secondary objective being an analysis of gender-specific disparities.

Detailed description: Acute myocardial infarctions resulting from unstable plaque in patients with coronary artery disease (CAD) account for a significant portion of cardiovascular morbidity and mortality. Although prediction models that incorporate traditional risk factors have been developed in order to risk stratify patients at highest risk for development of subsequent cardiovascular events, such models lack precision and are often found to over or under-estimate risk. Moreover, current clinical practice has focused on stenosis severity as a predictor of future plaque erosion and/or rupture, in spite of the fact that evidence from intravascular ultrasound (IVUS) studies, such as the PROSPECT trial, demonstrate that ACS events are more likely to occur in less than severely stenotic lesions. Furthermore, there is incomplete understanding of the influence of gender on atherosclerotic plaque composition and downstream coronary events, given the chronologic and prognostic differences between men and women in atherosclerotic cardiovascular disease.

Several studies have attempted elucidating characteristics of vulnerable plaque using invasive imaging modalities such as IVUS. However, such studies have several limitations, most significantly is the fact that plaque characterization was performed after an acute coronary event, which limits the ability to isolate baseline plaque characteristics from changes following the acute event. Noninvasive evaluation of atherosclerotic coronary disease using coronary computed tomographic angiography (CCTA) has been established as an accurate and readily available imaging modality in clinical practice. In addition to the evaluation of diameter stenosis, CCTA is capable of evaluation plaque composition as well as arterial remodeling, in a similar fashion to IVUS. The agreement between plaque characterization using IVUS and CCTA has been demonstrated in several large-scale trials. Nevertheless, there are several key aspects that have yet to be addressed, including the utility of plaque characterization by CCTA for determination of future cardiovascular events, and gender-based differences in atherosclerotic plaque composition in patients with stable and unstable coronary artery disease.

The ICONIC trial was designed as a nested case-control study based on the previously published CONFIRM registry, evaluating demographic, clinical as well as baseline CCTA-determined plaque composition in 238 patients with subsequent ACS events and 238 matched patients without ACS events. As previously described, ICONIC utilizes CCTA to comprehensively assess plaque morphology and characteristics, in addition to arterial wall changes in order to determine characteristics implicated in future adverse events, beyond what has been traditionally described using invasive imaging modalities. The primary goal is to investigate differences in atherosclerotic plaque composition in patients with ACS, compared to patients with stable coronary disease. The secondary goal is to determine gender-specific differences in plaque composition in both stable and unstable coronary artery disease.

Eligibility criteria: Cases:

Inclusion criteria:

* Age ≥18 years.
* Adjudicated STEMI / NSTEMI / UA / Unclassified MI (except for type 4a, 4b, or 5 MI)
* Baseline CCTA.

Exclusion criteria:

* Myocardial infarction not meeting the definition of ACS with missing cardiac biomarkers.
* Prior history of CAD (revascularization or MI).
* Prior revascularization (PCI or CABG).
* ACS in a previously revascularized segment.
* Type 4a, 4b, or 5 MI.

Controls

Inclusion criteria:

* Age ≥18 years.
* Propensity score matched.

Exclusion criteria:

* Prior history of CAD (revascularization or MI).
* Death as an outcome.

Primary outcomes:
measure: ACS
timeFrame: within 5 years
Secondary outcomes:
measure: STEMI and NSTEMI
timeFrame: within 5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Bethesda
country: United States
facility: Walter Reed Army Medical Center
state: Maryland
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Innsbruck
country: Austria
facility: Innsbruck Medical University
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Vancouver
country: Canada
facility: Providence Health Care St. Paul's Hospital
city: Munich
country: Germany
facility: University of Munich
city: Milan
country: Italy
facility: Department of Clinical Sciences and Community Health, University of Milan & Centro Cardiologico Monzino, IRCCS
city: Parma
country: Italy
facility: University Hospital of Parma
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Cardiovascular Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Lisboa
country: Portugal
facility: Hospital da Luz
Study officials:
affiliation: Weill Medical College of Cornell University
name: Leslee J Shaw, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Min JK, Dunning A, Lin FY, Achenbach S, Al-Mallah MH, Berman DS, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Cheng V, Chinnaiyan KM, Chow B, Delago A, Hadamitzky M, Hausleiter J, Karlsberg RP, Kaufmann P, Maffei E, Nasir K, Pencina MJ, Raff GL, Shaw LJ, Villines TC. Rationale and design of the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) Registry. J Cardiovasc Comput Tomogr. 2011 Mar-Apr;5(2):84-92. doi: 10.1016/j.jcct.2011.01.007. Epub 2011 Feb 1.
citation: Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, Inoue K, Okumura M, Ishii J, Anno H, Virmani R, Ozaki Y, Hishida H, Narula J. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol. 2007 Jul 24;50(4):319-26. doi: 10.1016/j.jacc.2007.03.044. Epub 2007 Jul 6.
citation: Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, Naruse H, Ishii J, Hishida H, Wong ND, Virmani R, Kondo T, Ozaki Y, Narula J. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol. 2009 Jun 30;54(1):49-57. doi: 10.1016/j.jacc.2009.02.068.
citation: Pflederer T, Marwan M, Schepis T, Ropers D, Seltmann M, Muschiol G, Daniel WG, Achenbach S. Characterization of culprit lesions in acute coronary syndromes using coronary dual-source CT angiography. Atherosclerosis. 2010 Aug;211(2):437-44. doi: 10.1016/j.atherosclerosis.2010.02.001. Epub 2010 Feb 10.
citation: Cheng VY, Nakazato R, Dey D, Gurudevan S, Tabak J, Budoff MJ, Karlsberg RP, Min J, Berman DS. Reproducibility of coronary artery plaque volume and composition quantification by 64-detector row coronary computed tomographic angiography: an intraobserver, interobserver, and interscan variability study. J Cardiovasc Comput Tomogr. 2009 Sep-Oct;3(5):312-20. doi: 10.1016/j.jcct.2009.07.001. Epub 2009 Jul 30.
citation: Pundziute G, Schuijf JD, van Velzen JE, Jukema JW, van Werkhoven JM, Nucifora G, van der Kley F, Kroft LJ, de Roos A, Boersma E, Reiber JH, Schalij MJ, van der Wall EE, Bax JJ. Assessment with multi-slice computed tomography and gray-scale and virtual histology intravascular ultrasound of gender-specific differences in extent and composition of coronary atherosclerotic plaques in relation to age. Am J Cardiol. 2010 Feb 15;105(4):480-6. doi: 10.1016/j.amjcard.2009.09.054. Epub 2010 Jan 5.