Atheroma; MyocardialPEPSiiNCT04701385
Plaque Erosion Prospective Study ii
An observational study of Atheroma; Myocardial, run by Norfolk and Norwich University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Atheroma; Myocardial
- What is being tested?
- Optical Coherence Tomography (OCT)
- How many people
- 33 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Oct 2020to 31 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Adult, Older adult
Study population: All comers myocardial infractions/stable angina cases to the NNUH Cardiology team
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, Norfolk, NR4 7UY
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Atheroma; Myocardial
- Being tested
- Optical Coherence Tomography (OCT)
- Keywords
- Plaque Erosion, Circulating endothelial cells, Myocardial infarction, Neutrophils
- Medical subject headings
- Plaque, Atherosclerotic, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Optical Coherence Tomography (OCT)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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Diagnostic Test: Optical Coherence Tomography (OCT) | |
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apoptotic circulating endothelial cells
The hypothesis is that plaque rupture myocardial infarctions are correlated with higher levels of circulating endothelial cells (100-1000 cells per ml) in blood compared to levels seen following a plaque rupture myocardial infarction (less than 100 cells per ml).To measure these levels, plasma will be taken from patient and a sample analysed using flow cytometry to determine the levels of circulating endothelial cells. Invasive assessment of their coronary arteries at the time of angioplasty with an OCT scanner will differentiate the patients cause of heart attack into plaque eruption or plaque rupture.
Measured: 1 year
Secondary outcomes (3)
Neutrophils
It has been shown in models that TLR2 on neutrophils is required for the formation of an erosion-like coronary plaque. Using blood samples to quantify numbers of neutrophils via flow cytometry whilst also looking at which of these population are positive for TLR2 (TLR2 activation encourages further expression of TLR2). This is feasibility data to see whether human plaque erosion myocardial infarctions are associated with TLR2 positive neutrophils as in the models. Invasive assessment of their coronary arteries at the time of angioplasty with an OCT scanner will differentiate the patients cause of heart attack into plaque eruption or plaque rupture.
Measured: 1 year
Endothelial progenitor cells
Endothelial Progenitor Cells (EPC) are a bone marrow derived cell line, the levels in blood at the time of a myocardial infarction correlate with a better prognosis from the myocardial infarction. Early EPCs (differentiated on flow cytometry CD34- / CD133+ / CD45+ / KDR+) have a paracrine function and promote angiogenesis. Late EPCs (differentiated on flow cytometry by CD34+ / CD133- / CD45dim / KDR+) can differentiate into endothelial cells. To measure the levels of EPCs (early and late) in blood of patients presenting with plaque erosion/rupture (as classified by OCT scanning at the time of angiography) and hypothesise plaque erosions will have higher levels (cells/ml) of these progenitor cells.
Measured: 1 year
Biomarker analysis
At present it is only possible to differentiate plaque erosion from plaque rupture at a post-mortem examination or by invasive OCT assessment. Biomarker differences (using cytokine arrays) between patients with plaque rupture and plaque erosion myocardial infarctions have levels of TSP-1 and EGF in peripheral blood correlated with plaque rupture, whereas levels of I-TAC positively correlate with plaque erosion. Frozen plasma samples taken peripherally will have further array (OLink Cardiovascular panel 3) to see if any of these molecules correlate with plaque erosion/rupture. Further validation will be sought through ELISA assessments. Invasive assessment of their coronary arteries at the time of angioplasty with an OCT scanner will differentiate the patients cause of heart attack into plaque eruption or plaque rupture. OLink panels do not give a level of the molecule in blood only a differential of the differences in cytokine levels.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2021
- Study start15 Oct 2020
- Primary completion31 Jan 2022
- Study completion31 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atheroma; MyocardialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Norfolk and Norwich University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James Wardley, Principal investigator, Specialist Trainee in Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04701385
- Sponsor's protocol ID
- 270706
- Acronym
- PEPSii
- Status last verified
- Nov 2023
- First submitted
- 6 Oct 2020
- Last updated
- 18 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plaque Erosion Prospective Study ii
- ClinicalTrials.gov ID
- NCT04701385
- Acronym / sponsor ID
- PEPSii / 270706
- Conditions
- Atheroma; Myocardial
- Keywords
- Plaque Erosion, Circulating endothelial cells, Myocardial infarction, Neutrophils
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Norfolk and Norwich University Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 8 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NSTEMI | – | Diagnostic Test: Optical Coherence Tomography (OCT)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 |
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- All comers myocardial infractions/stable angina cases to the NNUH Cardiology team
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Diagnostic test | NSTEMI |
Primary outcome
Apoptotic circulating endothelial cells
Time frame: 1 year
The hypothesis is that plaque rupture myocardial infarctions are correlated with higher levels of circulating endothelial cells (100-1000 cells per ml) in blood compared to levels seen following a plaque rupture myocardial infarction (less than 100 cells per ml).To measure these levels, plasma will be taken from patient and a sample analysed using flow cytometry to determine the levels of circulating endothelial cells. Invasive assessment of their coronary arteries at the time of angioplasty with an OCT scanner will differentiate the patients cause of heart attack into plaque eruption or plaque rupture.
3 secondary outcomes
Neutrophils
Time frame: 1 year
Endothelial progenitor cells
Time frame: 1 year
Biomarker analysis
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
- Individual participant dataSharing planned: No
Related trials for Atheroma; Myocardial
RecruitingObservational study
Identification of Asymptomatic Patients at Very High Cardiovascular Risk: Contribution of a Strategy Based on Carotid and Coronary Explorations, Compared to Simple Risk Calculation Using the European "SCORE 2" Algorithm. (IDEA-CVR)
Myocardial Infarction, Atheroma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Wardley principal investigator
Specialist Trainee in Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atheroma; Myocardial, run by Norfolk and Norwich University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apoptotic circulating endothelial cells (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023; AzTrials last refreshed its copy on 31 Oct 2026.