Microclots and Neutrophil Activation as Potential Indicators for Stroke Risk and Reperfusion Failure
CLOTSAFE
Micro-clots and Neutrophil Activation as Potential Indicators for Stroke Risk and Reperfusion Failure The CLOTSAFE - Study (Micro-CLOTs, Stroke Risk, Activated Neutrophils, Reperfusion FailurE)
1 other identifier
observational
500
1 country
1
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Feb 2025
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 28, 2024
CompletedFirst Posted
Study publicly available on registry
July 31, 2024
CompletedStudy Start
First participant enrolled
February 1, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
August 29, 2025
March 1, 2025
5.6 years
July 28, 2024
August 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 Outcomes (5)
Change in National Institute of Health Score Scale (NIHSS)
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)
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)
365 days
Incidence of new cardiovascular disease
365 days
All-cause mortality
365 days
Study Arms (5)
Control Group
Patients without previous documented stroke
Chronic Stroke Group
Patients with previous stroke ≥1year ago
Acute Stroke No Therapy Group
Patients with acute stroke, but without intravenous thrombolysis or mechanical thrombectomy
Acute Stroke IVT only Group
Patients with acute stroke and intravenous thrombolysis
Acute Stroke MT-Group
Patients with acute stroke and mechanical thrombectomy
Interventions
DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.
The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots
Micro-CT is a 3D imaging technique utilizing X-rays to see inside an object, slice by slice. Micro-CT, also called microtomography or micro computed tomography, is similar to hospital CT or "CAT" scan imaging but on a small scale with greatly increased resolution. Samples can be imaged with pixel sizes as small as 100 nanometers and objects can be scanned as large as 200 millimeters in diameter. We will use micro-CT to analyze blood clots from patients with large vessel occlusion.
Eligibility Criteria
Patients without acute stroke (Control Group and chronic Stroke Group) will be recruited at the neurovascular ambulatory of the University Hospital Zurich Patient with acute stroke will be included at the stroke unit of the University Hospital Zurich.
You may qualify if:
- Patients without acute stroke CS or CSG
- No previous stroke or previous stroke ≥ 1 year ago
- Signed informed consent
- Patients with acute stroke (AS-noTx, AS-IVT, AS-MT):
- Patients admitted with high suspicion of acute ischemic stroke
- Time of onset of stroke symptoms ≤ 12 hours
- Consent according to the regulations of research in an emergency situation
- Ischemic stroke later confirmed
You may not qualify if:
- All groups:
- Pregnancy
- Age under 18 years
- Acute Stroke no Therapy
- Acute treatment with IVT or with MT
- Acute Stroke IVT-Group • Acute treatment with MT or without IVT
- Acute Stroke MT-Group
- Acute treatment without MT
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University Hospital Zurich
Zurich, Canton of Zurich, 8091, Switzerland
Biospecimen
Blood sampling
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Susanne Wegener, Prof.
University Hospital Zurich, department Neurology
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr. med.
Study Record Dates
First Submitted
July 28, 2024
First Posted
July 31, 2024
Study Start
February 1, 2025
Primary Completion (Estimated)
September 1, 2030
Study Completion (Estimated)
December 1, 2030
Last Updated
August 29, 2025
Record last verified: 2025-03