Natural History of Coronary Atherosclerosis in Real-World Stable Chest Pain Patients Underwent Computed Tomography Angiography in Comparison With Invasive Multimodality Imaging

NCT02440646 | Terminated DMC

• 1 other identifier: REALITY Advanced
• Study Type: observational
• Target: 1,080
• Locations: 3 countries
• Sites: 4

Brief Summary

In a prospective international multicenter observational study, 1080 stable chest pain patients (REALITY Advanced registry of CCTA patients) with the suspected chronic coronary syndrome will be enrolled. All of them will undergo computed tomography angiography, CMR and/ or SPECT, and Echo. One of the cohorts will be examined with multimodality invasive imaging including quantitative coronary angiography, FFR, QFR with or without further percutaneous coronary intervention, OCT, and some of them - with IVUS, VH-IVUS. The plaque size and relevant stenosis, a composition of the atherosclerotic lesion, major adverse cardiovascular events (all-cause death, death from cardiac causes, myocardial infarction, or rehospitalization due to unstable or progressive angina, ischemia-driven revascularization) will be judged to be related to either originally treated (culprit) lesions or untreated (non-culprit) lesions. Moreover, the clinical potential of both non-invasive and invasive imaging, as well as anatomical vs functional modalities in two real-world patient flows, will be estimated with the special focus on the natural progression of atherosclerosis, clinical outcomes, and safety (contrast-induced nephropathy, radiocontrast-induced thyroid dysfunction, and radiation dose). The diagnostic accuracy will be analyzed. The follow-up period will achieve 12 months prospectively with collected clinical events and imaging outcomes which will be determined at the baseline and 12-month follow-up. The independent ethics expertise will be provided by the Ural State Medical University (Yekaterinburg, Russia) and Central Clinical Hospital of the Russian Academy of Sciences (Moscow, Russia). The monitoring of the clinical data with imaging as well as further CoreLab expertise (expert-level post-processing multimodal imaging software of Medis Imaging B.V., Leiden, The Netherlands) will be provided by De Haar Research Task Force, Amsterdam-Rotterdam, the Netherlands. FFR-CT is scheduled to be assessed by the ElucidVivo Research Edition software from Elucid Bio, Boston, MA, U.S.A. The REALITY project is a part of the JHWH (Jahweh) International Advanced Cardiovascular Imaging Consortium. The main objective of the Consortium that is uniting international efforts of both Academia and Industry is a synergistic development of the advanced machine-learning imaging software in order to integrate benefits of both non-invasive and invasive imaging providing the daily clinical practice with the robust tool for the anatomical and functional examination of coronary atherosclerosis, PCI-related arterial remodeling, and relevant myocardial function.

Conditions

Coronary Atherosclerosis; Coronary Artery Disease; Contrast-induced Nephropathy; Cerebrovascular Disease; Alzheimer Disease; Chronic Coronary Insufficiency; Stable Chronic Angina

Keywords

Computed tomography angiography; Quantitative coronary angiography; Coronary artery disease; Natural history of atherosclerosis; Radiocontrast-induced thyroid dysfunction; Contrast-induced nephropathy; Plaque burden; Glagovian artery remodeling; Radiation dose; SYNTAX score; Fractional flow reserve; Optical coherence tomography; Intravascular ultrasound; Intravascular imaging; Cardiac magnetic resonance; Echocardiography; Single photon emission computed tomography

Outcome Measures

Primary Outcomes (8)

• Change of per cent of plaque burden from baseline to follow-up as assessed by either CCTA or QCA

  Plaque burden for both culprit and non-culprit lesions will be calculated as a lesion volume (vessel volume-lumen volume)/lumen volume x 100. The variable will be adjusted for computed tomography angiography (CCTA) and quantitative coronary angiography (QCA) including the available methods of both noninvasive (CMR, SPECT) and invasive (OCT, IVUS, VH-IVUS) imaging.

  At 12 months after the baseline imaging procedure

• Number of participants with major adverse cardiac events that are related to plaque burden

  The composite of cardiac death, cardiac arrest, myocardial infarction, acute coronary syndrome, revascularization by coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI), or rehospitalization for angina for patients with both culprit- and non-culprit-lesion-related events. Event rates will be determined at: hospital, at 12 months. The results will be compared with the CCTA-related predictive model of the ElucidVivo Research Edition software from Elucid Bio, Boston, MA, U.S.A.

  At 12 months after the baseline imaging procedure

• Head-to-head comparison between non-invasive (CCTA, FFR-CT, CMR, SPECT, Echo) and invasive imaging (QCA, FFR, QFR, OCT, IVUS, VH-IVUS)

  A comparison will be performed to assess the diagnostic accuracy of both noninvasive and invasive imaging approaches for the detection of obstructive coronary artery disease, comprehensive characterization of atherosclerosis. The imaging data will be analyzed by the expert-level post-processing software.

  At baseline and 12 months after the baseline imaging procedure

• Non-invasive imaging for risk stratification

  To determine the prognostic value of CCTA, CMR, SPECT, and Echo handled with the expert-level post-processing software for predicting cardiac death and nonfatal myocardial infarction. The results will be compared with the CCTA-related predictive model of the ElucidVivo Research Edition software from Elucid Bio, Boston, MA, U.S.A.

  At 12 months after the baseline imaging procedure

• Invasive imaging for risk stratification

  To determine the prognostic value of QCA, FFR, QFR, OCT, IVUS, VH-IVUS, handled with the expert-level post-processing software for predicting cardiac death and nonfatal myocardial infarction. The results will be compared with the CCTA-related predictive model of the ElucidVivo Research Edition software from Elucid Bio, Boston, MA, U.S.A.

  At 12 months after the baseline imaging procedure

• Diagnostic accuracy of non-invasive and invasive imaging

  Determining the diagnostic accuracy of stand-alone cardiac imaging modalities including CCTA, CMR, SPECT, Echo, QCA, FFR, QFR, OCT, IVUS, VH-IVUS.

  At baseline and 12 months after the baseline imaging procedure

• Progression of atherosclerosis and plaque composition in comparison between non-invasive and invasive imaging methods

  The progression of atherosclerosis will be quantitatively characterized by the parameters of the lesions (e.g. plaque burden, cap thickness, arterial remodeling, presence of erosions or rupture, malaposition of stent, a vessel injury score and so on). The imaging data will be handled with the expert-level post-processing software.

  At baseline and 12 months after the baseline imaging procedure

• Comparison between anatomical and functional imaging modalities

  The anatomical (CCTA, CMR, SPECT, QCA, OCT, IVUS, VH-IVUS) and functional (MSCT, CMR, SPECT, Echo, FFR-CT, FFR, QFR) imaging modalities will be compared to assess the difference between the progression of coronary atherosclerosis, condition of blood flow, and myocardial function in the field of interest. The myocardium will be visualized with the CMR system Ingenia 3.0T (Philips, The Netherlands) or systems from any other vendors.

  At baseline and 12 months after the baseline imaging procedure

Secondary Outcomes (16)

• Change of serologic markers of inflammation from baseline to follow-up that are related to cardiovascular events and intervention

  At baseline and 12 months after the baseline imaging procedure

• Number of participants with procedural success

  At 12 months after the baseline imaging procedure

• Change of complexity of coronary artery disease from baseline to follow-up as assessed by SYNTAX score I

  At baseline and 12 months after the baseline imaging procedure

• Change of complexity of coronary artery disease from baseline to follow-up as assessed by SYNTAX score II

  At baseline and 12 months after the baseline imaging procedure

• Change of fractional flow reserve (FFR) from baseline to follow-up that are related to the progress of atherosclerosis

  At baseline and 12 months after the baseline imaging procedure

Study Arms (2)

CCTA group

All stable chest pain comers admitted to the chest-pain outpatient or inpatient cardiac center with the chronic coronary syndrome who underwent functional tests (CMR and/ or SPECT, and Echo are mandatory) and coronary computed tomography angiography (CCTA) without further immediate quantitative coronary angiography (QCA), applicable intravascular imaging (FFR, QFR, OCT, IVUS, VH-IVUS) and/ or percutaneous intervention (PCI).

Radiation: Coronary computed tomography angiography

CCTA + Invasive group

All stable chest pain comers admitted to the chest-pain outpatient or inpatient cardiac center with the chronic coronary syndrome who underwent functional tests (CMR, and/ or SPECT, and Echo are mandatory) and coronary computed tomography angiography (CCTA) with further quantitative coronary angiography (QCA), applicable intravascular imaging (FFR, QFR, OCT, IVUS, VH-IVUS) with or without implantation of a stent.

Radiation: Quantitative coronary angiography, intravascular imaging with percutaneous intervention

Interventions

Coronary computed tomography angiography RADIATION

The coronary arteries will be visualized with the MSCT scan CT 5000 Ingenuity (Philips, The Netherlands) or systems from any other vendors.

Also known as: CCTA

CCTA group

Quantitative coronary angiography, intravascular imaging with percutaneous intervention RADIATION

Coronaries will be shot with Artis zee (Siemens, Germany) or systems from any other vendors. In case if necessary the procedure will be delayed for intravascular imaging (FFR, QFR, OCT, IVUS, VH-IVUS) and/ or percutaneous intervention (with implantation of the medical device).

Also known as: QCA, Coronary intravascular imaging

CCTA + Invasive group

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All stable chest pain comers with a chronic coronary syndrome without acute angina who underwent CCTA (CMR, and/ or SPECT, and Echo are mandatory) and/ or QCA, applicable intravascular imaging (OCT, IVUS, VH-IVUS) with or without further PCI.

You may qualify if:

• all stable chest pain comers with chronic coronary syndrome or angina equivalent consistent with the manifestation of the stable coronary artery disease (by the 2019 Guidelines on Chronic Coronary Syndrome);
• age between 40 and 79 years old;
• patient must have one or two-vessel disease in a native coronary vessel requiring or not requiring PCI without indications for immediate bypass surgery with any SYNTAX score;
• lesions may be either de novo or restenotic;
• successful, uncomplicated PCI could be performed in the culprit vessels and all culprit lesions, but there should be no events or complications between the procedures of PCI in the past and six months before admission to the Chest Pain Center;
• the non-culprit vessel should have no flow-limiting lesions (but any plaque burden) and be available for imaging. The non-culprit vessel must be considered safe for imaging evaluation;

You may not qualify if:

• any acute comorbidities;
• patient has had a documented ST-elevation acute myocardial infarction within the 24 hours or acute coronary syndrome (unstable angina, myocardial infarction) during four weeks before admission to the Chest Pain Center;
• patient has had a recent PCI (last 6 months before admission to the Chest Pain Center) unless the patient is undergoing a staged procedure for dual vessel treatment;
• unprotected left main lesion location;
• imaging evidence of severe calcification (CCTA calcium scoring with a CAC\>1000) or marked tortuosity of the vessel;
• culprit lesion is located within or distal to an arterial or saphenous vein graft;
• untreated, significant coronary lesion with a \>50-75% diameter stenosis remaining in the culprit vessel after the planned intervention (branch stenosis is permitted) unless allowed by the Heart Team, or the Institutional Review Board (IRB), or the Data Safety and Monitoring Board (DSMB);
• lesion or vessel contains visible thrombus within the imaging procedure;
• patient has an additional lesion that requires intervention within 180 days after the initial hospitalization unless allowed by the Heart Team, or the IRB, or the DSMB;
• any diameter stenosis more than 75% in the non-culprit vessel;
• indications for immediate bypass surgery within one year of enrollment with the SYNTAX above 34 (including multi-vessel disease requiring intervention in all three major coronary arteries);
• decompensated hypotension or heart failure requiring intubation, inotropes, intravenous diuretics, or intra-aortic balloon counterpulsation (including the presence of cardiogenic shock);
• patient has a known left ventricular ejection fraction \<40% or history of decompensated congestive heart failure;
• uncontrolled tachycardia or refractory ventricular arrhythmia;
• presence of cardiac implants;

Sponsors & Collaborators

• Central Clinical Hospital of the Russian Academy of Sciences: lead
• Ural State Medical University: collaborator
• De Haar Research Task Force: collaborator
• Center of Endosurgery and Lithotripsy, Moscow, Russia: collaborator
• JHWH International Advanced Cardiovascular Imaging Consortium: collaborator
• Medis Medical Imaging Systems B.V.: collaborator
• Pie Medical Imaging B.V.: collaborator
• De Haar Research Foundation: collaborator

Study Sites (4)

De Haar Research Foundation

Tallinn, 10151, Estonia

Location

De Haar Research Task Force

Amsterdam, North Holland, 1069CD, Netherlands

Location

Center of Endosurgery and Lithotripsy, Moscow, Russia

Moscow, 111123, Russia

Location

Central Clinical Hospital of the Russian Academy of Sciences

Moscow, 117593, Russia

Location

Related Links

• Ural State Medical University/ USMU (former Ural State Medical Academy/ USMA)
• Center of Endosurgery and Lithotripsy, Moscow, Russia
• De Haar Research Task Force/ DHRF (aka De Haar Research Foundation)
• Central Clinical Hospital of the Russian Academy of Sciences/ CCH RAS
• Medis Medical Imaging Systems B.V.
• Pie Medical Imaging B.V.
• ElucidVivo Research Edition

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples to test the main hypothesis.

MeSH Terms

Conditions

Coronary Artery Disease; Cerebrovascular Disorders; Alzheimer Disease; Angina, Stable

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Alexander Kharlamov, M.D., FESC, FACC, FEACVI

  De Haar Research Task Force, Amsterdam-Rotterdam, The Netherlands

  STUDY CHAIR

• Alexey Sozykin, M.D., D.Sc.

  Central Clinical Hospital of the Russian Academy of Sciences

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator and coordinator of the REALITY project

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 12, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: August 1, 2022
• Last Updated: August 30, 2022

Record last verified: 2022-08

Locations

RU (2); ES (1); NL (1)