SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)

描述（由申请人提供）：在美国，近200万小皮质下中风（S3，又名腔隙性梗死）的幸存者具有复发性中风和发展为血管性痴呆的高风险。S3s是西班牙裔人群中最常见的中风亚型之一。小皮质下卒中二级预防（SPSS）试验的目的是确定预防S3患者卒中复发和认知能力下降的有效治疗方法。SPSS由两个随机的多中心临床试验组成，将招募2500名有症状的、mri定义的S3患者（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加氯吡格雷75 mg/d。2. 血压干预：“常规”高血压管理，收缩压目标为130 - 149毫米汞柱；“强化”高血压管理，收缩压目标<130 mm Hg。抗血小板比较是双盲的，而血压干预是开放标签的，事件的盲法评估。每3个月随访一次，平均随访3年。主要目标是：1。目的：确定联合抗血小板治疗在减少卒中复发和认知能力下降方面是否比单独使用阿司匹林更有效。2. 确定“强化”血压降至特定目标范围是否优于“常规”高血压管理，以减少卒中复发和认知能力下降。最初的申请建议在35个临床站点每月招募2名患者。随机化始于2003年，比预期的要低。为了解决这个问题，我们增加了更多的国内和国际站点，使活跃站点达到63个。在过去的一年中，招募人数稳定在每月40人左右，截至2007年2月1日，招募了1341名参与者。按照目前的招生速度，我们预计在2009年7月之前完成招聘，在此之后还将继续进行一年的后续工作。之前没有随机试验专门关注S3后的二级预防，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，或预防西班牙裔中风和痴呆。SPSS的结果可能会导致数百万S3患者，特别是西班牙裔患者中风和血管性痴呆负担的显著减少。本申请的目的是在最初招聘不足的情况下，请求支持SPS3试验的继续和完成。研究的设计和目标与最初的应用程序保持不变。

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.