SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)

小皮质下中风的二级预防 (SPS3)

• 批准号: 8184784
• 负责人: OSCAR R BENAVENTE
• 金额: $ 260.01万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-05 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8184784
• 关键词: Accounting; Address; Age; American; Anticoagulation; Antihypertensive Agents; Arteries; Aspirin; Blinded; Blood; Blood Pressure; Blood Vessels; Caring; Carotid Stenosis; Cerebrovascular Disorders; Cerebrum; Cervical; Clinical; Clinical Trials; Cognitive; Combined Modality Therapy; Coupled; Dementia; Disease; Double-Blind Method; Elderly; Endarterectomy; Enrollment; Epidemiology; Ethnic group; Event; General Population; Goals; Health Benefit; Hispanic Americans; Hypertension; Hypotension; Impaired cognition; Infarction; International; Intervention; Ischemic Stroke; Lead; Magnetic Resonance Imaging; Not Hispanic or Latino; Outcome Study; Participant; Patients; Population; Prevention; Prevention therapy; Randomized; Recurrence; Risk; Risk Factors; Risk Reduction; Safety; Sample Size; Secondary Prevention; Source; Stroke; Stroke prevention; Survivors; Testing; Vascular Dementia; Vascular Diseases; base; blood pressure regulation; clinical research site; clopidogrel; design; follow-up; high risk; indexing; nervous system disorder; open label; outcome forecast; prevent; primary outcome; prospective; randomized trial; response; standard of care

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.

描述（由申请人提供）：小皮质下卒中（S3）也称为腔隙性卒中，是一种常见的卒中亚型，占所有缺血性卒中的至少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，血管性痴呆的常见底物。超过200万的S3幸存者有复发性中风和血管性痴呆的风险;还有数百万人患有亚临床S3和小血管疾病引起的认知能力下降。小型皮质下卒中的二级预防（SPS 3）是一项国际随机、多中心临床试验，采用析因设计测试两种干预措施。它将招募3000名有症状的、MRI定义的S3、无颈动脉狭窄或主要心源性栓塞源的参与者（其中20%为西班牙裔美国人）。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：325 mg/d vs阿司匹林325 mg/d加氯吡格雷75 mg/d。 2.血压发明：收缩压目标为130至149 mmHg与<130 mmHg。抗血小板比较是双盲的，而血压干预是开放标签的，具有盲态评估和临床事件验证。每三个月随访一次，平均随访3年。主要研究结果为：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。联合抗血小板治疗在预防卒中复发和减少认知功能下降方面比单独使用阿司匹林更有效。 2.强化血压控制与更少的复发性中风和减少认知能力下降有关。 3.西班牙裔美国人与非西班牙裔白色参与者相比，中风和认知能力下降的绝对减少更大。截至2010年11月1日，2865例患者入组了66家目前活跃的临床研究中心。以前没有随机试验专门关注S3后卒中的二级预防，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，或预防西班牙裔美国人的卒中和痴呆。SPS 3的结果可能会大大减轻数百万S3患者，特别是西班牙裔美国人的严重神经系统疾病（中风和血管性痴呆）的负担。研究目的与原始申请保持不变。本申请的目的是请求支持继续和完成试验，因为样本量增加到500例受试者，所有受试者额外随访一年，以累积所需的主要事件数量。 公共卫生相关性：美国每年至少发生20万例皮质下小卒中（S3），近200万S3幸存者面临复发性中风和血管性痴呆的高风险。目前尚不清楚如何最佳地预防这一人群的卒中复发和认知障碍。SPS 3将通过在近期MRI定义的S3患者中测试两种干预措施来解决几个重要的临床和科学问题。这些结果将为数百万患有这种常见血管疾病的患者的管理提供信息。

项目成果

Postthrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute stroke patients: a systematic review and meta-analysis.

• DOI: 10.1111/j.1747-4949.2012.00869.x
• 发表时间: 2013-07
• 期刊: International journal of stroke : official journal of the International Stroke Society
• 作者: Shoamanesh A;Kwok CS;Lim PA;Benavente OR
• 通讯作者: Benavente OR

Monitoring futility in a two-by-two factorial design: the SPS3 experience.

监控二乘二因子设计中的无效性：SPS3 体验。

• DOI: 10.1177/1740774512474374
• 发表时间: 2013
• 期刊: Clinical trials (London, England)
• 作者: McClure,LeslieA;Coffey,ChristopherS;Howard,George
• 通讯作者: Howard,George

The Levels of Inflammatory Markers in the Treatment of Stroke study (LIMITS): inflammatory biomarkers as risk predictors after lacunar stroke.

• DOI: 10.1111/j.1747-4949.2010.00420.x
• 发表时间: 2010-04
• 期刊: International journal of stroke : official journal of the International Stroke Society
• 作者: Elkind MS;Luna JM;Coffey CS;McClure LA;Liu KM;Spitalnik S;Paik MC;Roldan A;White C;Hart R;Benavente O
• 通讯作者: Benavente O

Reliability and validity of blood pressure measurement in the Secondary Prevention of Small Subcortical Strokes study.

小皮质下中风二级预防研究中血压测量的可靠性和有效性。

• DOI: 10.1097/mbp.0b013e3280858d5b
• 发表时间: 2007
• 期刊: Blood pressure monitoring
• 影响因子: 1.3
• 作者: Pérgola,PabloE;White,CaroleL;Graves,JohnW;Coffey,ChristopherS;Tonarelli,SilvinaB;Hart,RobertG;Benavente,OscarR;SPS3Investigators
• 通讯作者: SPS3Investigators

The correlates and course of depression in patients with lacunar stroke: results from the Secondary Prevention of Small Subcortical Strokes (SPS3) study.

腔隙性中风患者抑郁症的相关性和病程：小皮质下中风二级预防 (SPS3) 研究的结果。

• DOI: 10.1159/000330350
• 发表时间: 2011
• 期刊: Cerebrovascular diseases (Basel, Switzerland)
• 作者: White,CaroleL;McClure,LeslieA;Wallace,PatriciaM;Braimah,Janet;Liskay,Alice;Roldan,Ana;Benavente,OscarR;SPS3Investigators
• 通讯作者: SPS3Investigators