SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)

描述(申请人提供)：近200万皮质下小中风的幸存者(S3，又名。在美国，腔隙性脑梗塞是中风复发和发展为血管性痴呆的高危人群。S3是西班牙裔中最常见的中风亚型之一。皮质下小卒中二级预防(SPSS)试验的目的是确定有效的治疗方法来预防S3患者的中风复发和认知能力下降。SPSS由两个随机的多中心临床试验组成，将招募2500名患有症状、MRI定义的S3的参与者(其中20%将是西班牙裔)。患者按析因设计分为两种干预措施：1.抗血小板干预：阿司匹林325 mg/d与阿司匹林325 mg/d加氯吡格雷75 mg/d。2.血压干预：常规的高血压治疗，收缩压目标为130至149毫米汞柱，而非阿司匹林325 mg/d。血压控制与收缩压目标&130毫米汞柱。抗血小板对照是双盲的，而血压干预是开放标签的，对事件的评估是盲目的。随访时间为每三个月一次，平均随访3年。主要目的是：1.确定联合抗血小板治疗在减少中风复发和认知功能下降方面是否比单用阿司匹林更有效。2.确定在降低中风复发和认知功能衰退方面，“高强度”降压至特定目标范围是否优于“常规”高血压治疗。最初的申请计划每月在35个临床地点招募2名患者。随机化始于2003年，低于预期。为了解决这一问题，我们增加了更多的国内和国际网站，使活跃网站达到63个。过去一年，招募人数稳定在每月40人左右，截至2007年2月1日，登记人数为1341人。按照目前的招生速度，我们预计在2009年7月之前完成征聘工作，在此之后还有一年的后续行动。此前没有一项随机试验专门关注S3之后的二级预防、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，或者专门针对西语裔人群的中风和痴呆症的预防。SPSS的结果可能会大大减轻数百万S3患者，尤其是拉美裔患者中风和血管性痴呆的负担。考虑到最初的征聘短缺，这项申请的目的是请求为继续和完成第三阶段特别方案的审判提供支助。研究的设计和目标与最初的应用保持不变。

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.