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)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Quantification and characterization of neutrophils
研究概览
简要总结
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
详细描述
Background:
Stroke remains a major health burden worldwide. Many patients are severely disabled and stay in need of care. Since introducing mechanical thrombectomy as a therapeutic option, clinical outcome has drastically improved over the last few years. However, despite successful macrovascular reperfusion (recanalization), patients with stroke still have a significant risk (about 40-50%) of remaining severely disabled, 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. Previous work in rodent stroke models demonstrated that removal of these capillary stalls indeed improves reperfusion and recovery after stroke. However, there is a lack of knowledge regarding the role of neutrophils or microclots in patients with stroke, and their potential to indicate reperfusion failure.
Aim:
The goal of our study is to search for activated neutrophils and microclots in peripheral blood samples from patients with stroke. We anticipate that neutrophil and microclot characteristics such as size, shape, or surface structure may indicate stroke risk, and may be associated with clinical outcome, stroke ethology and reperfusion failure in patients with stroke. Our goal is to improve the prediction of stroke risk and treatment success.
Methodology:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Quantification and characterization of neutrophils
时间窗: First Visit/Admission and patients with acute stroke after 24 hours, 3 months and 1 year
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)
Evaluation of reperfusion failure in patients with large vessel occlusion and mechanical thrombectomy
时间窗: <24 hours in patients with 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).
Quantification and characterization of microclots
时间窗: First Visit/Admission and patients with acute stroke after 24 hours, 3 months and 1 year
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)
次要结局
- 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)
- All-cause mortality(365 days)
- 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)
研究者
Susanne Wegener
Prof. Dr. med.
University of Zurich