The Origin and Role of Thromboembolism in the Pathogenesis of Ischaemic Stroke
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- The primary outcome measure will be the degree and location of platelet activation as determined by the target to background ratio of 18F-GP1.
研究概览
简要总结
Ischaemic stroke is usually due to occlusion of a cerebral artery by thrombus. However, it is often difficult to identify the source of thrombus, or to confirm thrombus as a cause of ischaemic stroke. Moreover, it is debated whether thrombosis plays any role in certain types of stroke such as lacunar stroke. In preliminary studies, the investigators have evaluated a novel clinical grade thrombus-specific radiotracer, 18F-GP1, which has a high specificity for the glycoprotein IIb/IIIa receptor on activated platelets. The investigations have demonstrated that 18F-GP1 is highly sensitive to in vivo thrombus formation and demonstrates avid binding to thrombus associated with myocardial infarction, pulmonary embolism and aortic bioprosthesis. This study will use this imaging approach to define the role and origin of thrombus in patients with ischaemic stroke, cryptogenic stroke and lacunar stroke.The investigators will also assess its added clinical value in assessing patients with ischaemic stroke.
详细描述
Stroke remains the second leading cause of death and the commonest cause of dependency in adults worldwide. The majority of strokes (80%) are due to cerebral ischaemia with a minority caused by subarachnoid (5%) or intracerebral (15%) haemorrhage.
Some stroke classification systems are based on the presumed mechanism, such as the Trial of Org 10172 in Acute Stroke Treatment (TOAST), the Causative Classification System (CCS) and the Atherosclerosis Small Vessel Disease Cardiac Source Other cause Dissection (ASCOD) classifications. These systems assign individual patients to cardioembolic, atherothromboembolic, lacunar (due to intrinsic disease of the cerebral perforating arterioles), other, or uncertain causes of stroke. However, a substantial proportion of patients (up to 25%) remain in the 'undetermined' category, because they have several potential overlapping causes, are incompletely investigated or are 'cryptogenic' where no cause has been identified.
Cryptogenic Stroke:
Cryptogenic stroke may have an embolic origin, supported by a pattern of brain infarction typically seen in patients with a definite embolic source: mainly cortical and affecting multiple vascular territories. In a systematic review, 1 in 6 ischaemic strokes were cryptogenic (~17%; range 9 to 25%) and in the Oxford Vascular Study of 2555 patients with a first ischaemic stroke, 1 in 3 were cryptogenic. Unfortunately, these patients have a high risk of recurrent ischaemic stroke (~25% at 5 years) that is comparable to those with known causes of stroke, indicating the need for better understanding and treatment of cryptogenic stroke. Two large randomised controlled trials compared direct oral anticoagulant therapies with aspirin to prevent stroke recurrence in patients with cortical cryptogenic strokes, testing the hypothesis that many of these strokes were due to an unidentified cardioembolic source (particularly paroxysmal atrial fibrillation). However, anticoagulant therapies were not superior to aspirin in preventing recurrent stroke and carried an increased risk of bleeding. Thus, the optimal preventative strategy in patients with cryptogenic stroke remains open for further exploration, and likely requires better patient stratification (i.e. selecting out those with occult thromboembolism) and understanding of its pathogenesis.
Lacunar Stroke:
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
- 否
入选标准
- •Males and females ≥18 years old
- •Diagnoses of acute ischaemic stroke (within 21 days of symptom onset) as per American Heart and Stroke Association guidelines
排除标准
- •Inability or unwillingness to provide informed written consent (ie lack capacity)
- •Inability to undergo the scanning protocol including ability to transfer onto the scanner
- •Women of child- bearing potential in whom pregnancy cannot be excluded
- •Contraindication to PET-CT scanning including estimated glomerular filtration rate <30 mL/min/1.73 m2
- •Participation in the study would result in a delay to carotid endarterectomy surgery
- •Known allergy to iodinated contrast or radiotracer
- •Severe or significant comorbidity precluding ability to complete study procedures.
- •Haemorrhagic stroke
- •Contra-indication to Magnetic Resonance imaging for those patients requiring a MRI Head
研究组 & 干预措施
Ischaemic Stroke
干预措施: 18F-GP1 PET/CT (Diagnostic Test)
Ischaemic Stroke
干预措施: Agitated Contrast Echocardiogram (Diagnostic Test)
Ischaemic Stroke
干预措施: MRI Head (Diagnostic Test)
Ischaemic Stroke
干预措施: ECG Monitoring (Diagnostic Test)
结局指标
主要结局
The primary outcome measure will be the degree and location of platelet activation as determined by the target to background ratio of 18F-GP1.
时间窗: < 21 days
次要结局
- Identifying the presence and site of platelet activation in cryptogenic and lacunar strokes.(< 21 days)
- Identifying sites of platelet activation in patients with atrial fibrillation or atrial flutter.(< 21 days)
- Measuring the presence of platelet activation in cardio-embolic, artery to artery and in situ arterial thrombosis.(< 21 days)
- Correlation and comparison between platelet activation with excised carotid atheroma in patients referred for carotid endarterectomy.(< 21 days)