Ignite Creation Date:
2024-05-06 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 1:53 PM
Study NCT ID:
NCT04701385
Status:
COMPLETED
Last Update Posted:
2023-12-18
First Post:
2020-10-06
Brief Title:
Plaque Erosion Prospective Study ii
Sponsor:
Norfolk and Norwich University Hospitals NHS Foundation Trust
Organization:
Norfolk and Norwich University Hospitals NHS Foundation Trust
Study Overview
Official Title:
Plaque Erosion Prospective Study ii
Status:
COMPLETED
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PEPSii
Brief Summary:
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
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:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None