MultiPlaque: Multiomics and Imaging-based Assessment of Vulnerable Coronary Plaques in Acute Coronary Syndromes

Sponsor

Cardio Med Medical Center (Industry)

Overall Status

Completed

CT.gov ID

NCT03391908

Collaborator

(none)

100

Enrollment

Location

Actual Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of Multiplaque clinical study is to assess the vulnerability degree of the atheromatous plaques, before and after a myocardial infarction (MI), based on multiomics analysis, associated with invasive and non-invasive data. In this study, a multi-parametric model for risk prediction will be developed, for evaluation of the risk that is associated with the vulnerable coronary plaques in patients that have suffered an acute coronary syndrome.

In the study, evaluation of the imaging characteristics of these coronary plaques will be performed with the use of CT, OCT, IVUS and invasive angiography. We will study the correlation between plaque evolution and (1) the degree of vulnerability at baseline, (2) multiomics profile of the patients and (3) clinical evolution during follow-up.

Also, new techniques for evaluation of the functional significance of coronary stenoses will be studied and validated, such as calculation of the fractional flow reserve or determination of shear stress in areas that are localized within the near vicinity of the vulnerable coronary plaques.

Condition or Disease	Intervention/Treatment	Phase
Coronary Stenosis Acute Coronary Syndrome Acute Myocardial Infarction Atheromatous Plaques Atherosclerosis Unstable Angina Non-ST Elevation Myocardial Infarction	Diagnostic Test: cardiac imaging tests

Detailed Description

This is a prospective cohort monocentric study.

The primary objective of this study is to research the vulnerability degree of ateromatous plaques before and after a myocardial infarction, based on multiomics data, invasive and non-invasive imaging data, in order to characterize the vulnerable coronary plaque and the vulnerable patient, in patients who have suffered an acute coronary syndrome (unstable angina or acute myocardial infarction).

The secondary objectives of the study are:

Evaluation of factors associated with the risk for reinfarction in patients with vulnerable plaques, according to their imaging characteristics of vulnerability.
Evaluation of predictive factors for reinfarction in patients with vulnerable plaques, according to the multiomics profile of the patient.
Determination of the rate of adverse events and MACE rates (Major Adverse Cardiac Events) according to the vulnerability degree of the coronary plaque at the index moment.
Evaluation of the efficiency of new methodologies for assessing vulnerable plaques: coronary shear stress determination, trans-stenotic contrast gradient, quantification of coronary plaque components through CT, OCT and IVUS.
Evaluation of the efficiency of non-invasive methodologies for assessment of the hemodynamic significance of coronary stenoses.

Study population: The study lot will be comprised by 100 patients out of which:

lot 1 (substudy 1) - 50 patients with unstable angina type acute coronary syndrome
lot 2 (substudy 2) - 50 patients with acute myocardial infarction (STEMI or NSTEMI) that occurred 30 days before randomization.

Study design and procedures:

Substudy 1: Research of vulnerable plaques in patients with ACS - Unstable angina

Baseline- Day 1: The following procedures will be performed at baseline:

Personal data recording (age, gender, address, contact);
anamnesis, cardiovascular risk assessment, comorbidities;
Physical examination
Laboratory analysis (biochemistry Cell blood count, troponin assay, hsCRP, matrix metalloproteinases, miRNAs, multiomic analysis)
ECG
Echocardiography (LVEF, chamber volumes and diameters, transmitral valvular flow, pulmonary artery pressure, 3D analysis of the regional kinetics with speckle tracking and tissue Doppler, evaluation of valvular regurgitation)
Myocardial perfusion echocardiography
Cardiac computed tomography
Perfusion CT
Coronary Angiography +/- stent implantation for the culprit lesion
Optical coherence tomography
Intravascular ultrasound

Follow-up:

Month 1 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation
Month 3 - telephone follow-up
Month 6 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation
Month 12 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation
Month 15 - telephone follow-up
Month 18 - telephone follow-up
Month 24 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation, Cardiac Computed Tomography, Perfusion CT

Substudy 2: Research of remaining vulnerable plaques in patients who have suffered an acute myocardial infarction (STEMI or NSTEMI), with maximum 30 days before the enrollment. The index event is considered to be the acute myocardial infarction.

Baseline - day 1: The following procedures will be performed at baseline:

Personal data recording (age, gender, address, contact);
Anamnesis, cardiovascular risk assessment, comorbidities;
Physical examination;
Laboratory analysis (biochemistry, Cell blood count, troponin assay, hsCRP, matrix metalloproteinases, miRNAs, multiomic analysis)
ECG
Echocardiography (LVEF, chamber volumes and diameters, transmitral valvular flow, pulmonary artery pressure, 3D analysis of the regional kinetics with speckle tracking and tissue Doppler, evaluation of valvular regurgitation)
Myocardial perfusion echocardiography
Cardiac computed tomography
Perfusion CT
Coronary Angiography +/- stent implantation for the culprit lesion
Optical coherence tomography

Follow-up:

Month 1 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation
Month 3 - telephone follow-up
Month 6 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation
Month 12 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation
Month 15 - telephone follow-up
Month 18 - telephone follow-up
Month 24 - anamnesis, physical examination, ECG, echocardiography, end-point evaluation, Cardiac Computed Tomography, Perfusion CT

Study Design

Study Type:

Observational

Actual Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Prospective Monocentric Clinical Study for Multiomics and Imaging-based Assessment of the Vulnerable Coronary Plaques and Associated Risk in Patients Who Presented an Acute Coronary Syndrome

Actual Study Start Date :

Apr 1, 2018

Actual Primary Completion Date :

Sep 30, 2020

Actual Study Completion Date :

Jan 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
MP - SG 01 Patients with unstable angina type acute coronary syndrome: patients aged at least 18 years, who have signed the informed consent, and present an unstable angina-type acute coronary syndrome with maximum 48h before presentation, defined as the presence of typical angina pain, with duration of more than 5 minute, accompanied by ECG changes.	Diagnostic Test: cardiac imaging tests Patients will undergo non-invasive Cardiac Computed Tomography for assessment of coronary plaques and myocardial perfusion, and invasive intracoronary imaging tests (coronary angiography, Intravascular ultrasound, optical coherence tomography and FFR). If imaging will reveal existence of a significant coronary plaque, a percutaneous coronary intervention (PCI - stenting) will be performed.
MP - SG 02 Patients with acute myocardial infarction (STEMI or NSTEMI) that occurred 30 days before randomization: patients aged at least 18 years, who have signed the informed consent, and present with acute myocardial infarction (STEMI or NSTEMI) defined as typical changes on the ECG (ST elevation of minimum 1 mm in at least 2 consecutive leads - STEMI; ST-T changes for NSTEMI) accompanied by increased levels of cardiac troponin I or T, or CK-MB of more than 2x the normal reference value of the laboratory.	Diagnostic Test: cardiac imaging tests Patients will undergo non-invasive Cardiac Computed Tomography for assessment of coronary plaques and myocardial perfusion, and invasive intracoronary imaging tests (coronary angiography, Intravascular ultrasound, optical coherence tomography and FFR). If imaging will reveal existence of a significant coronary plaque, a percutaneous coronary intervention (PCI - stenting) will be performed.

Arm

Intervention/Treatment

MP - SG 01

Patients with unstable angina type acute coronary syndrome: patients aged at least 18 years, who have signed the informed consent, and present an unstable angina-type acute coronary syndrome with maximum 48h before presentation, defined as the presence of typical angina pain, with duration of more than 5 minute, accompanied by ECG changes.

Diagnostic Test: cardiac imaging tests

Patients will undergo non-invasive Cardiac Computed Tomography for assessment of coronary plaques and myocardial perfusion, and invasive intracoronary imaging tests (coronary angiography, Intravascular ultrasound, optical coherence tomography and FFR). If imaging will reveal existence of a significant coronary plaque, a percutaneous coronary intervention (PCI - stenting) will be performed.

MP - SG 02

Patients with acute myocardial infarction (STEMI or NSTEMI) that occurred 30 days before randomization: patients aged at least 18 years, who have signed the informed consent, and present with acute myocardial infarction (STEMI or NSTEMI) defined as typical changes on the ECG (ST elevation of minimum 1 mm in at least 2 consecutive leads - STEMI; ST-T changes for NSTEMI) accompanied by increased levels of cardiac troponin I or T, or CK-MB of more than 2x the normal reference value of the laboratory.

Diagnostic Test: cardiac imaging tests

Outcome Measures

Primary Outcome Measures

rate of major clinical endpoints - acute myocardial infarction - occuring in the follow-up period [2 years]
The rate of infarction (in the group of unstable angina) or re-infarction (in the group with already established myocardial infarction) will be assessed during the 2-year follow-up and correlated with the degree of plaque vulnerability as determined by imaging tests.

Secondary Outcome Measures

Revascularization rate [2 years]
The need for revascularization of the culprit lesion and of the non-culprit lesions will be assessed during the 2-year follow-up
Rate of progression of the vulnerability degree of the coronary plaques [1 year]
The vulnerability degree of each coronary lesion will be assessed by Cardiac CT at base-line and at 1-year follow-up, and the progression/regression of the vulnerability degree will be calculated
MACE rates (Major Adverse Cardiovascular Events) [2 years]
Major adverse cardiac events represented by cardiac death, all-cause death, rehospitalization rate, target vessel revascularization and re-infarction rate

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Substudy 1:

Patients aged at least 18 years
Patients who have signed the informed consent
Unstable angina type acute coronary syndrome with maximum 48h before presentation, defined as the presence of typical angina pain, with duration of more than 5 minute, accompanied by ECG changes.

Substudy 2:

Patients aged at least 18 years
Patients who have signed the informed consent
Acute myocardial infarction (STEMI or NSTEMI) defined as typical changes on the ECG (ST elevation of minimum 1 mm in at least 2 consecutive leads - STEMI; ST-T changes for NSTEMI) accompanied by increased levels of cardiac troponin I or T, or CK-MB of more than 2x the normal reference value of the laboratory.

Exclusion Criteria: (for both substudies)

Known sensibility for the contrast agents
Women at reproductive age who does not use contraceptive methods
Pregnant women
Any malignancy within the last 5 years
Acute or chronic renal failure
Any disease or comorbidity that reduces the life expectancy under 2 years
Non-compliant patients who, in the opinion of the investigators, will not undergo the follow-up process