Stroke and Coated-Platelets - A Translational Research Initiative
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 134
- 试验地点
- 1
- 主要终点
- new silent brain infarctions
研究概览
简要总结
Silent brain infarctions (SBIs) are a manifestation of covert cerebrovascular disease, without obvious clinical deficit, noted very often in patients presenting with a new stroke or new transient ischemic attack. SBIs are linked to a significant increase in risk for subsequent stroke and cognitive decline. However, no biomarker is currently available that can predict the recurrence of these subclinical lesions. Coated-platelets are a measure of platelet procoagulant potential significantly increased in patients with ischemic stroke or transient ischemic attack compared to unaffected controls. Higher coated-platelet levels are strongly associated with both the presence and number of SBIs. Among medications approved for preventing stroke recurrence, the investigators identified clopidogrel as a pharmacological agent leading to a decrease in coated-platelet levels. In this project, the investigators plan to evaluate if clopidogrel can decrease the rate of occurrence of new silent brain infarctions. The result will enhance the investigators understanding of the relationship between platelets and silent brain infarcts, leading to improved health care delivery and also potential targets for novel preventive pharmacological interventions.
详细描述
Introduction:
Silent brain infarcts (SBIs) are a recently recognized, commonly noted and yet poorly understood finding of cerebral infarction on imaging studies without a clinically apparent neurological deficit. The availability of high resolution brain imaging such as Magnetic Resonance Imaging (MRI) has made the recognition and characterization of these covert markers of cerebrovascular disease possible. SBIs, also referred to as silent strokes, are subcortical cavities or cortical areas of gliosis presumed to be caused by previous infarction.
The prevalence of SBIs in the general population ranges between 8 and 28% in large cardiovascular and aging studies performed in Europe and North America. A key finding has been that prevalence rates are relatively low before age 65 with a gradual increase seen with aging. Among vascular risk factors, hypertension has the strongest association with SBIs, however other vascular risk factors, such as stroke, have been associated with increased prevalence of these lesions. The overall prevalence of SBI far exceeds that of symptomatic stroke and is estimated that for every symptomatic stroke there are approximately 10 SBIs.
Incidence data for SBIs are sparse, likely a reflection of the need for repeat imaging studies. Incidence in the general population is estimated at 3% and 6.5% per year from large population studies. A high incidence of SBIs has been reported following procedures such as aortic valve replacement or carotid endarterectomy, likely directly related to these procedures. Research data in a cohort of Transient Ischemic Attack (TIA) patients who underwent initial MRI at the time of the diagnosis and then repeat brain MRI one year after the index event showed a 37% incidence of new SBIs.
There has been considerable evidence linking SBIs with an increased risk for subsequent occurrence of stroke, development of cognitive decline and mortality, suggesting that SBIs are precursors of more severe ischemic brain disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The two stroke neurologists reviewing the brain MRI scans will independently adjudicate the presence and number of SBIs for each patient by reviewing the initial and repeat scans, along with the medical history. Each adjudicator will maintain a log with the results and a study identification number while blinded to the platelet procoagulant levels and intervention arm distribution. The laboratory staff will be blinded to clinical, imaging and intervention data. The VA Research Pharmacy will dispense similar looking pills to ensure the double-blind nature of the intervention.
入排标准
- 年龄范围
- 21 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosis of ischemic stroke/TIA
- •<90 days from onset of symptoms
- •initial MRI available
- •not receiving antiplatelet therapy at the time of admission
- •medical decision by the treating physician that antiplatelet therapy is indicated for secondary prevention (decision independent of the study and based on individual clinical decision for each patient).
- •baseline coated-platelet levels at 40%
- •willingness to participate in the study for 24 months
排除标准
- •dementia (based on chart review or self/proxy report)
- •> 90 days from onset of symptoms
- •initiation of anticoagulation or thrombolytics prior to phlebotomy
- •intracranial hemorrhage or bleeding diatheses
- •end-stage renal disease (ESRD)
- •inability to tolerate consenting or phlebotomy
- •prior adverse/allergic reactions to clopidogrel
- •treating physician deemed a different antiplatelet dose or dual antiplatelet therapy as the only treatment choice
研究组 & 干预措施
Clopidogrel
After randomization, patients will receive clopidogrel mg daily for the duration of the study. The VA Research Pharmacy will dispense similar looking pills (using a "dummy pill") with Arm 2 to ensure the double-blind nature of the intervention. Clopidogrel is FDA approved for secondary prevention of stroke. Patients will be followed for 24 months with repeat brain MRI scans obtained at 24 months.
干预措施: Clopidogrel treatment (Drug)
Aspirin
After randomization, patients will receive aspirin daily for the duration of the study. The VA Research Pharmacy will dispense similar looking pills (using a "dummy pill") with Arm 1 to ensure the double-blind nature of the intervention. Aspirin is FDA approved for secondary prevention of stroke. Patients will be followed for 24 months with repeat brain MRI scans obtained at 24 months.
干预措施: Aspirin treatment (Drug)
结局指标
主要结局
new silent brain infarctions
时间窗: 24 months
Each of the two reviewers will independently adjudicate the presence, location and number of SBIs for each patient by reviewing both the initial and repeat scans at 24 months.
次要结局
- cognitive impairment(24 months)