Microclots and Neutrophil Activation as Potential Indicators for Stroke Risk and Reperfusion Failure
NCT Number: NCT06530927
Acronym: CLOTSAFE
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Ischemic Stroke
Interventions: DIAGNOSTIC_TEST: 3D rotational digital tomography|DIAGNOSTIC_TEST: Atomic Force Microscopy|DIAGNOSTIC_TEST: Micro-Computertomography
Sponsor: University of Zurich
Collaborators: Empa, Swiss Federal Laboratories for Materials Science and Technology
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 500
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09-01
Completion Date: 2030-12-01

Summary:
Stroke remains a major health burden worldwide. Many patients are severely disabled and stay in need of care. Mechanical thrombectomy has dramatically improved outcomes for stroke patients with large vessel occlusions, yet 40-50% of patients with successful recanalization remain severely disabled despite successful recanalization, a scenario called "futile recanalization". One of the causes for this lack of treatment effect is capillary obstruction, or "no reflow", potentially resulting from activated neutrophils and micrometer-sized blood clots. To address this issue, we employ digital holotomographic and atomic force microscopy to investigate the structural and chemical characteristics of blood and clot material in stroke patients and individuals at high risk of developing a stroke. Our study elucidates the association of activated neutrophils and microclots with stroke risk, and may be associated with clinical outcome, stroke ethology and reperfusion failure in patients with stroke. Leveraging label-free microscopy tools, could potentially lead to the discovery of new biomarkers for individualized stroke treatment and prevention, ultimately offering rapid identification of at risk patients and improving clinical outcomes

Primary Outcome Measures: Quantification and characterization of microclots, 3D rotational digital tomography and atomic force microscopy

imaging outcome measurements:

* size: length (µm), width (µm)
* dry mass (g/dl)
* praevalence (count in numbers)
* composition (platelet aggregate vs. fibrin-rich microclots vs. microclot composite), First Visit/Admission and patients with acute stroke after 24 hours, 3 months and 1 year|Quantification and characterization of neutrophils, 3D rotational digital tomography and atomic force microscopy

image morphological outcome measurements:

* size: diameter (µm), surface area (µm2), volume (fl), thickness (µm), sphericity
* dry mass (g/dl)
* praevalence (count in numbers)
* activation state (activated vs. not activated vs. dead), First Visit/Admission and patients with acute stroke after 24 hours, 3 months and 1 year|Evaluation of reperfusion failure in patients with large vessel occlusion and mechanical thrombectomy, Defined by successfull macrovascular reperfusion (TICI \>=2c) and insufficient microvascular reperfusion with the outcome measurment (yes/no)

Successfull macrovasular reperfusion is defined according to the mTICI score 2c or 3.

Microvascular reperfusion success will be evaluated with thresholds were used to discriminate between microvascular hypoperfusion and reperfusion, calculated from perfusion images obtained on computed tomography (CTP) or magnetic resonance perfusion imaging (MRP)., <24 hours in patients with mechanical thrombectomy
Secondary Outcome Measures: Change in National Institute of Health Score Scale (NIHSS), will be assessed using National Institutes of Health Stroke Scale (NIHSS)

NIHSS

13 assessed functional domains Range 0-42, higher score indicates severe impairment, First Visit/Admission and patients with acute stroke after 24 hours, 3 months and 1 year|Degree of disability or dependence assessed by the modified ranking scale (mRS), will be assessed using modified Rankin Scale (mRS)

mRS

Range: (0-6) 0 = no symptoms, 6 = death, higher score indicates severe impairment, First Visit/Admission and patients with acute stroke after 24 hours, 3 months and 1 year|Assessment Quality of Life using European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L), EQ-5D-5L

Evaluation of 5 different aspects of health with likert scale (1-5)

MOBILITY SELF-CARE USUAL ACTIVITIES PAIN / DISCOMFORT ANXIETY / DEPRESSION Each domain is scored individually, higher values indicate higher impairment of quality of life, 365 days|Incidence of new cardiovascular disease, Stroke, heart attack, brain bleeding, 365 days|All-cause mortality, Mortality, 365 days