SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)

描述(申请人提供)：皮质下小卒中(S3)，也称为腔隙性卒中，是一种常见的卒中亚型，至少占所有缺血性卒中的25%。在西班牙裔美国人中，S3是一种常见的中风亚型，发生在相对年轻的年龄。S3通常是由于小血管疾病，这是血管性痴呆的常见底物。超过200万的S3幸存者面临中风复发和血管性痴呆的风险；还有数百万人患有亚临床S3和小血管疾病导致的认知能力下降。皮质下小卒中二级预防(SPS3)是一项以析因设计测试两种干预措施的国际随机多中心临床试验。它将招募3000名参与者(其中20%将是西班牙裔美国人)，他们患有MRI定义的有症状的S3，没有颈动脉狭窄或主要的心脏栓塞源。按析因设计，患者被分配到两种干预措施中：1.抗血小板干预：325毫克/天，阿司匹林325毫克/天，氯吡格雷75毫克/天。2.血压发明：收缩压目标为130-149毫米汞柱，而不是130毫米汞。抗血小板比较是双盲的，而血压干预是开放标签的，临床事件的评估和验证是盲目的。随访时间为每三个月一次，平均3年。主要研究结果是：1)复发性中风(缺血性和出血性)，2)认知能力下降，3)主要血管事件SPS3的关键假设是：1.联合抗血小板治疗在预防中风复发和减少认知能力下降方面比单独使用阿司匹林更有效。2.加强血压控制与减少中风复发和减少认知功能衰退有关。3.与非西班牙裔白人参与者相比，拉美裔美国人中风和认知能力下降的绝对降幅更大。截至2010年11月1日，在66个目前活跃的临床站点登记了2865名患者。此前没有一项随机试验专门关注S3后中风的二级预防，中风后血压控制的最佳目标水平及其与认知能力下降的关系，或者西班牙裔美国人中风和痴呆症的预防。SPS3的结果可能会大大减轻数百万S3患者，特别是拉美裔美国人的严重神经系统疾病(中风和血管性痴呆症)的负担。研究目标与最初的申请保持不变。这项申请的目的是请求为继续和完成试验提供支助，因为增加了500名参与者的样本规模，并为所有受试者增加了一年的后续行动，以积累所需数量的主要事件。 公共卫生相关性：美国每年至少发生200,000例皮质下小中风(S3)，其中近200万S3幸存者具有复发中风和血管性痴呆的高风险。目前尚不清楚如何在这一人群中以最佳方式预防中风复发和认知障碍。SPS3将通过在最近的MRI定义的S3患者身上测试两种干预措施来解决几个重要的临床和科学问题。这一结果将为数百万患有这种常见血管疾病的患者的治疗提供参考。

DESCRIPTION (provided by applicant): Small subcortical strokes (S3) also known as lacunar strokes, are a common stroke subtype accounting for at least 25% of all ischemic strokes. In Hispanic Americans, S3 are a frequent stroke subtype and occur at a relatively young age. S3 are usually due to small vessel disease, a common substrate for vascular dementia. Over two million survivors of S3 are at risk for recurrent stroke and for vascular dementia; millions more suffer sub-clinical S3 and cognitive decline caused by small vessel disease. Secondary Prevention of Small Subcortical Strokes (SPS3) is an international randomized, multicentre clinical trial testing two interventions in a factorial design. It will enroll 3000 participants (20% of whom will be Hispanic Americans) with symptomatic, MRI-defined S3 without carotid stenosis or major cardio-embolic sources. Patients are assigned, in a factorial design, to two interventions: 1. Antiplatelet Intervention: 325 mg/d vs. aspirin 325 mg/d plus clopidogrel 75 mg/d. 2. Blood Pressure Invention: systolic blood pressure targets of 130 to 149 mmHg vs. <130 mmHg. The antiplatelet comparison is double-blinded, while the blood pressure intervention is open- label with blinded assessment and verification of clinical events. Follow-up is every three months for a mean of 3 years. Main study outcomes are: 1) recurrent stroke (ischemic and hemorrhagic), 2) cognitive decline, 3) major vascular events The key hypotheses for SPS3 are: 1. Combination antiplatelet therapy is more efficacious than aspirin alone for prevention of stroke recurrence and for reduction in cognitive decline. 2. Intensive blood pressure control is associated with fewer recurrent strokes and reduction in cognitive decline. 3. The absolute reduction in stroke and cognitive decline will be greater in Hispanic Americans vs. non-Hispanic white participants. As of November 1, 2010, 2865 patients were enrolled in 66 currently active clinical sites. No previous randomized trials have focused specifically on secondary prevention of stroke after S3, on optimal target levels of blood pressure control after stroke and their relationship to cognitive decline, or on prevention of stroke and dementia in Hispanic Americans. The results of SPS3 will likely lead to important reductions in the burden of serious neurological diseases (stroke and vascular dementia) for millions of people with S3, and particularly for Hispanic Americans. The study objectives remain unchanged from the original application. The purpose of this application is to request support for continuation and completion of the trial necessitated by the increase in sample size of 500 participants and an additional year of follow up for all subjects in order to accrue the required number of primary events. PUBLIC HEALTH RELEVANCE: At least 200,000 small subcortical strokes (S3) occur annually in the U.S., with nearly two million S3 survivors at high risk for recurrent stroke and vascular dementia. It remains unclear how to optimally prevent stroke recurrence and cognitive impairment in this population. SPS3 will address several important clinical and scientific questions by testing two interventions in patients with recent MRI-defined S3. The results will inform the management of millions of patients with this common vascular disorder.