Plaque Erosion Prospective Study ii

NCT ID: NCT04701385

Last Updated: 2023-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

33 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-10-15

Study Completion Date

2023-01-31

Brief Summary

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Plaque erosion is associated with myocardial infarction (MI) in about 30% of cases and may require a different management approach to plaque rupture. The investigators hypothesise that plaque erosion leads to higher levels of apoptotic circulating endothelial cells (CECs) compared to plaque rupture.

Aims: To compare associations between plaque erosion and plaque rupture with numbers and types of apoptotic CECs in patients with non-ST elevation MI (NSTEMI) and stable coronary artery disease controls (CAD). Additional aims are to explore signals of cellular stress (mitochondrial dsDNA), sub-populations of activated neutrophils, circulating endothelial progenitor cells and erosion-specific plasma biomarkers.

Methods: Prospective observational study of 80 patients with NSTEMI and 40 patients with stable CAD. Plaque erosion or rupture will be identified by intracoronary Optical Coherence Tomography (OCT). CECs and neutrophils will be quantified and characterised using flow cytometry looking at markers of cell death and neutrophil activation. Plasma will be analysed by proteomic methods (Olink) and for mitochondrial dsDNA.

Potential importance of findings: This study will provide evidence for the hypothesised mechanism of plaque erosion and clarify if biomarker analysis in NSTEMI patients provides a basis for non-invasive diagnosis of plaque erosion versus rupture.

Detailed Description

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This is a prospective observational pilot study to assess the feasibility of studying endothelial cell and neutrophil differences between coronary atherosclerotic plaque rupture and plaque erosion in patients presenting with NSTEMI. The data obtained from this study will be used to determine the feasibility of a larger study, if appropriate.

Patients presenting with a diagnosis of NSTEMI within 24 hours of chest pain will be approached to take part in the study if an invasive strategy is planned. A control group of patients scheduled to undergo elective PCI for stable angina will also be recruited.

Following written informed consent peripheral venous blood samples will be taken as soon as possible after admission (or immediately prior to elective PCI in the control group) this will be analysing using flow cytometry to determine circulating cell sub-populations. Stored plasma will be used for proteomic analysis (separate funding to be sought). Cellular populations will be isolated and characterised by transcriptome analysis using RNA-seq (separate funding to be sought).

The culprit lesion will be identified by coronary angiography in the NSTEMI group, and if feasible OCT will be undertaken in the culprit and non-culprit vessels. If OCT is not feasible (eg lesion requires pre-dilatation with a balloon, or vessel is too tortuous) the patient will be excluded from the study and no further study related procedures will be undertaken. Blood samples from such patients will also be discarded.

OCT data will be analysed off line by two independent experts to classify plaque morphology (rupture, erosion, other). Endothelial cell populations will be analysed in coronary and peripheral arterial blood using flow cytometry: results will be analysed according to OCT-defined plaque pathology.

Blood samples will be stored with a view to proteomic analysis using the Olink Cardiovascular panel.

The patients will be contacted at 1 month by telephone to determine vital status and adverse events.

Conditions

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Atheroma; Myocardial

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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NSTEMI

Patients presenting with a myocardial infarction will have blood samples taken for analysis. At the time of their angiography/angioplasty procedure they will have an OCT assessment of the culprit coronary artery to distinguish if the heart attack was caused by a plaque rupture or plaque erosion event

Optical Coherence Tomography (OCT)

Intervention Type DIAGNOSTIC_TEST

Optical Coherence Tomography (OCT) can undertake detailed characterisation of plaque morphology in patients with myocardial infarction at the time of percutaneous treatment. This allows plaque rupture, erosion and other mechanisms of myocardial infarction to be differentiated

Control

Patients undergoing planned angioplasty will have blood samples taken pre and post angioplasty to help as a control for the flow cytometry and for biomarker analysis

No interventions assigned to this group

Interventions

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Optical Coherence Tomography (OCT)

Optical Coherence Tomography (OCT) can undertake detailed characterisation of plaque morphology in patients with myocardial infarction at the time of percutaneous treatment. This allows plaque rupture, erosion and other mechanisms of myocardial infarction to be differentiated

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Provision of written informed consent, \< 75 years old
* NSTEMI group: Admission to hospital within 24 hr of pain onset. Scheduled to undergo invasive angiography ± PCI during index admission
* Stable angina group: Scheduled to undergo elective PCI

Exclusion Criteria

* Cardiogenic shock or haemodynamic instability,
* NSTEMI due to stent thrombosis restenosis, coronary dissection or embolism
* Previous CABG
* Requirement for mechanical ventilation
* Known severe renal impairment (eGFR \<45 ml/min/1.73m2)
* Known haematological malignancy or systemic inflammatory disorder
* Requirement for emergency cardiac surgery
* Inability to carry out OCT
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Norfolk and Norwich University Hospitals NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Wardley

Role: PRINCIPAL_INVESTIGATOR

Specialist Trainee in Cardiology

Locations

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Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, Norfolk, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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270706

Identifier Type: -

Identifier Source: org_study_id

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