Therapeutic Window for Acute Stroke Therapy (P50)

描述（由申请人提供）：加州大学圣地亚哥分校（UCSD）卒中中心的急性卒中转化研究专业项目（SPOTRIAS）目前利用4个核心的资源开展了3项相互关联的临床试验，旨在满足SPOTRIAS增加溶栓治疗患者数量的总体目标。在5年的更新期内，我们建议通过6项新的临床试验推进这一议程：（1）中风治疗中的血管内冷却-咖啡醇（ICTuS-C），建立在ICTuS-L正在进行的低温研究轨道上，从证明血管内冷却与溶栓结合的可行性和安全性发展到与Houston SPOTRIAS合作评估安全性，在3小时窗口内出现的急性缺血性卒中患者中血管内诱导低温和咖啡醇的可行性和早期疗效;（2）急性卒中中的经颅超声，其建立在正在进行的超声成像研究轨道上，以研究诊断超声与rt-PA和/或超声造影剂微泡联合用于图像引导经颅溶栓的潜力;（3）使用数字观测摄像机的中风团队远程评估-优化执业者在中风中的使用（STRokE DOC OPUS），它建立在正在进行的视听远程医疗研究轨道上，通过确定我们开创性的轴辐模型是否可以在其他社区复制以及下一代，优化技术将增加STRokE DOC系统在互联网技术有限的地区的使用;（4）反搏升级中风前向流（CUFFS），一项新的试点评估，评估急性缺血性中风患者在症状发作0-48小时内无创外部反搏（ECP）的耐受性，可行性和安全性;（5）tPA+经颅发射低能量激光用于急性卒中恢复的安全性（StELLAR），这是NeuroThera激光系统与rt-PA的首次联合研究;和（6）预测和治疗ICH生长的斑点征（STOP IT），一项急性脑内血肿的研究，旨在确定CT血管造影预测血肿生长的敏感性和特异性，并测试CT血管造影的可行性。血管造影指导止血治疗。总之，我们的SPOTRIAS更新期提案旨在进一步整合和综合UCSD卒中中心在进行转化研究方面的相当大的优势，最终使我们地理实践范围内和全球范围内的卒中患者受益，因为我们治疗更多2小时以下的患者，并探索新的方法来安全有效地治疗3小时rt-PA窗口之外的其他指南不合格患者，包括通过改进患者选择和分层以及与溶栓结合并可能增强溶栓的额外治疗。

DESCRIPTION (provided by applicant): The Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) at the University of California San Diego (UCSD) Stroke Center currently applies the resources of 4 Cores to conduct 3 interrelated clinical trials designed to meet the overarching SPOTRIAS goal of increasing the number of thrombolytic-treated patients. Over the course of the 5-year renewal period, we propose to move this agenda forward with 6 new clinical trials: (1) Intravascular Cooling in the Treatment of Stroke-Caffeinol (ICTuS-C), which builds on the ongoing hypothermia research track of ICTuS-L, evolving from demonstration of the feasibility and safety of intravascular cooling in combination with thrombolysis to collaborative assessment, with Houston SPOTRIAS, of the safety, feasibility, and early efficacy of the endovascular induction of hypothermia and caffeinol in acute ischemic stroke patients presenting within the 3-hour window; (2) Transcranial Ultrasound in Acute Stroke, which builds on the ongoing ultrasound imaging research track to study the potential of diagnostic ultrasound in combination with rt-PA and/or ultrasound contrast agent microbubbles on image-guided transcranial thrombolysis; (3) Stroke Team Remote Evaluation Using a Digital Observation Camera - Optimizing Practitioners' Use in Stroke (STRokE DOC OPUS), which builds on the ongoing audio-visual telemedicine research track to explore the utility of remote telemedicine consultations for acute stroke by determining whether our pioneering hub-and-spoke model can be replicated in other communities and whether next-generation, optimized technology will increase use of the STRokE DOC system in areas with limited access to Internet-based technology; (4) Counterpulsation to Upgrade Forward Flow in Stroke (CUFFS), a new pilot assessment of the tolerability, feasibility, and safety of noninvasive external counterpulsation (ECP) in acute ischemic stroke patients within 0-48 hours of symptom onset; (5) Safety of tPA plus Transcranial Emission of Low-Energy Lasers for Acute Stroke Recovery (StELLAR), the first combination study of the NeuroThera Laser System with rt-PA; and (6) Spot Sign for Predicting and Treating ICH Growth (STOP IT), a study of acute intracerebral hemorrhages to determine the sensitivity and specificity of CT angiography for the prediction of hematoma growth and to test the feasibility of CT angiography for the guidance of hemostatic therapy. Altogether, our SPOTRIAS proposal for the renewal period aims to integrate and synthesize further the considerable strengths of the UCSD Stroke Center in conducting translational research that ultimately benefits stroke victims within our geographical practice range and worldwide as we treat more patients under 2 hours and explore new ways to safely and effectively treat other, guideline-ineligible patients outside the 3-hour rt-PA window, including through improved patient selection and stratification and additional treatments combined with and potentially augmenting thrombolysis.