Blood Pressure after Endovascular Stroke Therapy-II: A Randomized Trial

项目摘要 研究项目：血管内机械血栓切除术（EVT）后的血压（BP）管理， 大血管急性缺血性卒中（AIS）可严重影响脑再灌注， 结果。目前的指南建议在EVT后24小时内允许高于正常血压， 有力的证据我们的初步结果表明，EVT后收缩压（SBP）降低与 更好的结果。尽管假设低SBP目标会损害脑灌注，但没有数据表明 明确证明伤害与EVT后SBP目标之间的任何关系。这种安全性评价较低 收缩压目标是进行更大规模研究以评估其改善结果的功效的关键先决条件 接受EVT治疗的患者。我们将进行脑卒中血管内治疗后的血压-II（BEST-II） 试验中，120名成功接受EVT治疗的AIS患者将被随机分配到三个SBP目标（180英镑， <160和<140 mmHg），以1）评估较低SBP目标的危害和2）确定 （假设为≥ 25%）的III期有效性试验，该试验旨在降低SBP目标，以改善患者 结果。为了评估伤害，我们将检验零假设，即较低的SBP目标不会使大脑恶化 缺血或患者90天功能结局超过安全水平。该提案将产生 高质量的数据，用于大型多中心疗效试验的规划。总的来说，这一系列试验将导致 AIS患者EVT后最佳BP管理的循证指南生成。 候选人：在过去的两年里，伊娃米斯特里博士与她的导师密切合作，设计，领导， 成功完成了一项大型、前瞻性、多机构研究（BEST-I），以证明 EVT治疗的AIS患者SBP较低，结局改善。这一提议是由此产生的直接结果 前期工作她的长期目标是成为新型设计和急性中风电子促进的领导者 试验，以确保有效测试新的中风治疗方法，并改善患者的结果。 职业发展：为了实现她的长期目标，Mistry博士将遵循综合职业发展计划， 计划她的严格培训将包括课程作业，导师和顾问的个性化指导， 体验式培训，以掌握1）在急性和重症监护环境中的试验实施，2）适应性 和平台试验设计，3）临床试验的电子促进，以及4）领导技能。 环境：范德比尔特大学医学中心（VUMC）是美国最大的综合性中风中心。 田纳西州中部，每年进行100多次EVT。作为临床和转化科学奖 拥有大量NIH资助的研究人员和急性和重症监护临床试验领导者的机构， 新颖的试验设计，生物统计学和临床信息学，VUMC提供了一个理想的环境， 为Mistry博士成功实现她的研究和职业目标提供机会和支持资源， 成为独立调查员。

PROJECT SUMMARY Research Project: Blood pressure (BP) management after endovascular mechanical thrombectomy (EVT) for large vessel acute ischemic stroke (AIS) can critically influence brain reperfusion, and thereby patient outcomes. Current guidelines recommend allowing higher than normal BP in the 24 hrs after an EVT without strong evidence. Our preliminary results demonstrate that lower post-EVT systolic BP (SBP) associate with better outcomes. Although low SBP targets are assumed to compromise brain perfusion, no data exist to definitely demonstrate any relationship of harm with post-EVT SBP targets. Such safety assessment of lower SBP targets is a critical prerequisite to conduct larger studies to evaluate their efficacy in improving outcomes of EVT-treated patients. We will conduct the Blood Pressure after Endovascular Stroke Therapy-II (BEST-II) trial, where 120 AIS patients successfully treated with an EVT will be randomized to three SBP targets (£180, <160, and <140 mmHg) to 1) assess the harm of lower SBP targets and 2) determine the probability (hypothesized to be ³25%) of a positive phase III efficacy trial of lower SBP targets to improve patient outcomes. To assess the harm, we will test the null hypotheses that lower SBP targets do not worsen brain ischemia or 90-day functional outcome in patients beyond a level considered safe. This proposal will generate high quality data for the planning of a large, multicenter efficacy trial. Collectively, this set of trials will lead to evidence-based guideline generation for the optimal post-EVT BP management in AIS patients. Candidate: Working close with her mentors over the past two years, Dr. Eva Mistry designed, led, and successfully completed a large, prospective, multi-institutional study (BEST-I) to demonstrate the association of improved outcomes with lower SBP in EVT-treated AIS patients. This proposal is the direct result of this preliminary work. Her long-term goal is to be a leader in novel designs and electronic facilitation of acute stroke trials to ensure efficient testing of new stroke treatments and improve patient outcomes. Career Development: To achieve her long-term goal, Dr. Mistry will follow an integrated career development plan. Her rigorous training will include coursework, personalized mentoring from mentors and advisors, and experiential training to achieve mastery in 1) trial implementation in acute and critical care settings, 2) adaptive and platform trial designs, 3) electronic facilitation of clinical trials, and 4) leadership skills. Environment: Vanderbilt University Medical Center (VUMC) is the largest comprehensive stroke center in the middle Tennessee and performs over 100 EVTs annually. As a Clinical and Translational Science Awarded institution with a large pool of NIH-funded investigators and leaders in acute and critical care clinical trials, novel trial designs, biostatistics, and clinical informatics, VUMC provides an ideal environment with myriad opportunities and support resources for Dr. Mistry to successfully accomplish her research and career goals to become an independent investigator.