SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)

描述（由申请人提供）：近200万小皮质下中风（S3，又名）的幸存者。在美国，腔隙性脑梗死（腔隙性脑梗死）是复发性中风和发展为血管性痴呆的高风险。S3是西班牙裔人中最常见的中风亚型之一。小型皮质下卒中二级预防（SPSS）试验的目的是确定预防S3患者复发性卒中和认知功能下降的有效疗法。SPSS由两项随机、多中心临床试验组成，将招募2500名有症状、MRI定义的S3受试者（其中20%为西班牙裔）。在析因设计中，患者被分配到两种干预措施：1.抗血小板干预：阿司匹林325 mg/d vs.阿司匹林325 mg/d+氯吡格雷75 mg/d。2.血压干预：收缩压目标为130至149 mm Hg的“间歇性”高血压管理与收缩压目标<130 mm Hg的“强化”高血压管理。抗血小板比较是双盲的，而血压干预是开放标签的，对事件进行盲态评估。每三个月随访一次，平均随访3年。主要目标是：1。确定联合抗血小板治疗是否比阿司匹林单药治疗更有效地减少卒中复发和认知能力下降。2.确定“强化”血压降低至特定目标范围是否上级“常规”高血压管理，以减少复发性卒中和认知能力下降。原始申请拟在35家临床试验机构每月入组2例患者。随机化始于2003年，低于预期。为了解决这个问题，我们增加了更多的国内和国际网站，使活跃的网站达到63个。在过去一年中，招募人数稳定在每月40人左右，截至2007年2月1日，共有1 341人参加。按照目前的招募速度，我们预计将在2009年7月完成招募，并在此之后继续进行一年的随访。以前没有随机试验专门关注S3后的二级预防，卒中后血压控制的最佳目标水平及其与认知能力下降的关系，或预防西班牙裔人的卒中和痴呆。SPSS的结果可能会大大减轻数百万S3患者的中风和血管性痴呆负担，特别是西班牙裔患者。本申请的目的是，鉴于初始招募不足，请求支持继续和完成SPS 3试验。研究设计和目的与原始申请相比保持不变。

DESCRIPTION (provided by applicant): Nearly two million survivors of small subcortical strokes (S3, a.k.a. lacunar infarcts) in the U.S. are at high risk for recurrent stroke and for developing vascular dementia. S3s are one of the most common stroke subtypes in Hispanics. The aims of the Secondary Prevention of Small Subcortical Strokes (SPSS) trial are to define efficacious therapies for prevention of recurrent stroke and cognitive decline in patients with S3. SPSS consists of two randomized, multi-center clinical trials and will enroll 2500 participants (20% of whom will be Hispanic) with symptomatic, MRI-defined S3. Patients are assigned to two interventions in a factorial design: 1. Anti-platelet Intervention: aspirin 325 mg/d vs. aspirin 325 mg/d plus clopidogrel 75 mg/d. 2. Blood Pressure Intervention: 'Usual' hypertension management with systolic blood pressure targets of 130 to 149 mm Hg vs. 'Intensive' hypertension management with systolic blood pressure targets <130 mm Hg. The anti-platelet comparison is double-blinded, while the blood pressure intervention is open-label with blinded assessment of events. Follow-up is every three months for an average of 3 years. The primary aims are: 1. To determine whether combination anti-platelet therapy is more efficacious than aspirin alone for reducing stroke recurrence and cognitive decline. 2. To determine whether 'intensive' blood pressure lowering to a specific target range is superior to 'usual' hypertension management for reducing recurrent strokes and cognitive decline. The original application proposed to enroll 2 patients per month at 35 clinical sites. Randomization started in 2003 and was lower than anticipated. In order to address this problem, we have added additional domestic and international sites, bringing active sites to 63. Recruitment has stabilized at around 40 participants per month over the past year and as of February 1, 2007, 1341 participants were enrolled. At the current rate of enrollment, we anticipate completing recruitment by July 2009, with one additional year of follow-up continuing past that time. No previous randomized trials have focused specifically on secondary prevention 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 specifically in Hispanics. The results of SPSS will likely lead to an important reduction in the burden of stroke and vascular dementia for millions of people with S3, and particularly for Hispanics. The purpose of this application is to request support for continuation and completion of the SPS3 trial given the initial recruitment shortfall. The study design and objectives remain unchanged from the original application.