Comprehensive Assessment of Morphometric, Functional, Biomechanical and Biological Interactions Between Atherosclerotic Plaque and Platelets Within the Stenosed Coronary Artery

Atherosclerosis Clinical Trial

— INTERFORCE  

Official title:

Comprehensive Assessment of Morphometric, Functional, Biomechanical, and Biological Interactions Between Atherosclerotic Plaque and Blood Platelets Within the Stenosed Coronary Artery in Vivo: a Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06275399
• Other study ID #: INTERFORCE
• Status: Recruiting
• Start date: July 21, 2023
• Est. completion date: July 21, 2026

Study information

• Verified date: February 2024
• Source: Medical University of Warsaw
• Contact: Mariusz Tomaniak
• Phone: +48 22 5991951
• Email: mariusz.tomaniak[@]wum.edu.pl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The main objective of the present study is to verify, in vivo, whether shear forces computed solely based on coronary angiography and computational fluid dynamics (CFD) techniques are associated with the biomarkers indicating the prothrombotic tendency of circulating blood in situ - distally and proximally to the coronary stenosis. The study will prospectively assess the relationship between i) the value and distribution of shear rate and shear stress (SS) estimated using three-dimensional angiography and CFD techniques, and ii) atherosclerotic plaque characteristics as assessed by optical coherence tomography (OCT), iii) functional parameters of diseased vessels assessed by vessel fractional flow reserve (vFFR), and iv) in situ platelet activation, as expressed by platelet-derived microvesicles (pMVs) and small extracellular vesicles (sEVs), platelet aggregometry and other serum prothrombotic or inflammatory biomarkers sampled within the coronary artery.

Description:

The biomechanical forces, including shear rate and shear stress exerted by circulating blood on the coronary wall and on circulating blood elements have been reported to contribute to the processes of plaque destabilization and thrombosis. Reliable estimation of shear (shear rate and shear stress) acting in vivo within the coronary artery has now become possible using imaging data and computational fluid dynamics techniques. The changing microenvironment of the plaque has a crucial role in the biochemical processes involved in remodeling the plaque itself. In this prospective, single-center study a total of 105 patients will be enrolled presenting with chronic coronary syndrome and angiographically confirmed coronary stenosis (30% - 90%) amenable to OCT imaging (according to the operator's judgment).

The groups will be assessed at the time of angiography with:

• OCT examination for precise evaluation of plaque morphology within the coronary stenosis

• Computational fluid dynamics with vFFR and estimation of value and distribution of shear rate and shear stress

• Impedance aggregometry-based platelet reactivity

• Single-particle high-resolution flow cytometry analysis of platelet-derived microvesicles and small extracellular vesicles (sEVs) as well as additional platelet activation (P-selectin, annexin-V) and inflammatory biomarkers

• Proteomic and metabolomic characterization - in the subset of patients Biomarker assessment will be done in the blood sampled directly from coronary artery (proximal and distal segment).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: July 21, 2026
• Est. primary completion date: July 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic coronary syndrome

• Angiographically confirmed coronary stenosis (30% - 90%)

• Amenable to OCT imaging

Exclusion Criteria:

• Cardiogenic shock

• ST-segment elevation or non-ST-segment elevation myocardial infarction

• Active bleeding

• Left main coronary artery disease

• Multivessel disease

• Lesions located at a distance =3 mm from the ostium of the vessel

• Thrombocytopenia

• Previous coronary artery bypass grafting

• Previous coronary intervention with stent implantation or balloon angioplasty

• Previous use of novel oral anticoagulants or vitamin K antagonists

Related Conditions & MeSH terms

• Atherosclerosis
• Chronic Coronary Syndrome
• Plaque, Atherosclerotic

Intervention

Diagnostic Test:
• OCT examination
OCT examination for precise evaluation of plaque morphology within the coronary stenosis.
• Blood sampling
Blood sampling directly from coronary artery (proximal and distal segment) arteries
• Assessment of vFFR and shear stress parameters
The procedure is based on non-invasive assessment of vFFR and shear stress parameters with dedicated software, deriving parameters directly from coronary angiography with the calculation based on the computational fluid dynamics

Locations

Country	Name	City	State
Poland	Medical University of Warsaw	Warsaw	Mazowieckie

Sponsors (4)

Lead Sponsor	Collaborator
Medical University of Warsaw	National Science Centre, Poland, Queen Mary University of London, University College, London

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between the mean shear rate and shear stress values at the lesion's site and the concentration of pMVs and sEVs sampled in the distal segment of the artery.		Baseline
Secondary	Correlation between the shear stress measurements at the site of the lesion and the concentration of inflammatory biomarkers in the distal segment of the artery	Inflammatory biomarkers will include sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-a, PlGF, IL-6, IL-18, IL-10, CCL2	Baseline
Secondary	Correlation between the shear stress measurements at the site of the lesion and the platelet reactivity parameters in the distal segment of the artery	Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests	Baseline
Secondary	Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) concentration of the pMVs and sEVs		Baseline
Secondary	Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) concentration of inflammatory biomarkers	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-a, PlGF, IL-6, IL-18, IL-10, CCL2	Baseline
Secondary	Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) of platelet reactivity	Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests	Baseline
Secondary	Concentrations of inflammatory biomarkers categorized by the atherosclerotic plaque morphology and the mean value of shear stress affecting the endothelium at the stenosis site and as well as according to the vessel	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-a, PlGF, IL-6, IL-18, IL-10, CCL2	Baseline
Secondary	Platelet reactivity levels categorized by the atherosclerotic plaque morphology and the mean value of shear stress affecting the endothelium at the stenosis site and as well as according to the vessel	Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests	Baseline
Secondary	Concentrations of pMVs and sEVs categorized by the atherosclerotic plaque morphology and the mean value of shear stress affecting the endothelium at the stenosis site and as well as according to the vessel		Baseline
Secondary	Platelet reactivity levels in blood sampled from the stenosed vs. the non-stenosed coronary artery	Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests	Baseline
Secondary	Concentrations of analyzed pMVs and sEVs in blood sampled from the stenosed vs. the non-stenosed coronary artery		Baseline
Secondary	Concentrations of analyzed inflammatory biomarkers in blood sampled from the stenosed vs. the non-stenosed coronary artery	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-a, PlGF, IL-6, IL-18, IL-10, CCL2	Baseline
Secondary	Correlation between vFFR delta pressure and the delta platelet reactivity in stenosed artery compared to these gradients in a non-stenosed artery in the same patient	Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests	Baseline
Secondary	Correlation between vFFR delta pressure and the delta concentration of the pMVs and sEVs in stenosed artery compared to these gradients in a non-stenosed artery in the same patient		Baseline
Secondary	Correlation between vFFR delta pressure and the delta concentration of the inflammatory biomarkers in stenosed artery compared to these gradients in a non-stenosed artery in the same patient	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-a, PlGF, IL-6, IL-18, IL-10, CCL2	Baseline