Normobaric O2 in Ischemic Stroke

常压 O2 在缺血性中风中的应用

• 批准号: 7880555
• 负责人: ANEESH B SINGHAL
• 金额: $ 25.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7880555
• 关键词: Acute; Admission activity; Air; Alteplase; Animals; Atmospheric Pressure; Attenuated; Biochemical; Biological Markers; Blood - brain barrier anatomy; Brain; Brain hemorrhage; Breathing; Cell Death; Clinical; Clinical Trials; Coagulation Process; Conflict (Psychology); Controlled Clinical Trials; Data; Diffuse; Diffusion; Double-Blind Method; Edema; Enrollment; Ensure; Failure; Filament; Free Radicals; Future; Goals; Growth; Hour; Human; Hyperbaric Oxygen; Hyperbaric Oxygenation; Hypercapnic respiratory failure; Hyperoxia; Hypoxia; Inbred SHR Rats; Infarction; Injury; Intention; Ischemia; Ischemic Stroke; Lesion; Magnetic Resonance Imaging; Modeling; Molecular; Monitor; Multi-Institutional Clinical Trial; Nervous System Physiology; Neurologic; Outcome; Oxygen; Oxygen Therapy Care; Patients; Perfusion; Placebo Control; Public Health; Randomized; Reperfusion Therapy; Rodent; Rodent Model; Safety; Scanning; Stroke; Testing; Therapeutic; Therapy Clinical Trials; Time; Tissues; Translational Research; United States National Institutes of Health; Work; X-Ray Computed Tomography; acute stroke; base; brain tissue; cost; effective therapy; experience; hemodynamics; human data; human study; improved; insight; neuroprotection; prevent; programs; stroke therapy; thrombolysis

Breathing high-flow oxygen at normal atmospheric pressure (Normobaric Oxygen Therapy, NBO) may be a simple strategy to sustain ischemic brain tissue ('buy time') until spontaneous or therapeutic reperfusion occurs, and thereby improve stroke outcome. By preventing early ischemic cell death, NBO may be a useful adjunctive therapy that extends the narrow (3-hour) time window for IV tissue plasminogen activator (tPA) therapy. Our recent rodent and pilot human stroke studies provide compelling evidence that early NBO confers potent neuroprotection. While the benefit appears to be transient, similar to that observed in prior hyperbaric oxygen studies, sustained benefit does occur if NBO-treated ischemic tissue is later reperfused. In this proposal (Spotrias Project 1), we aim to extend our preliminary work in a double blind, randomized, placebo-controlled clinical trial enrolling 240 acute (< 9 hours) ischemic stroke patients over 5 years. Patients will receive either NBO or Room Air for 8 hours and undergo serial clincial assessments and CT scans. NBO's therapeutic potential will be assessed in an "intention to treat" statistical analysis of change in NIHSS scores during therapy. The potential synergistic benefit of NBO with reperfusion will be assesed in patients who undergo a baseline and a 24-hour CT-perfusion scan to assess reperfusion, as part of Project 2 (Lev). Other secondary analyses will include an assessment of post-therapy clinical function scores, brain hemorrhage rates, and lesion volume growth on CT scans. In year 1 we will exclude tPA-treated patients and investigate the safety and utility of combined NBO with tPA in embolic (clot-based) rodent stroke models. If the combined therapy appears safe in rodents, and if the year 1 human data raises no safety concerns, we will include tPA-treated patients in the clinical trial of NBO. From these studies we hope to collect preliminary data and gain pilot experience for a future multi-center trial of NBO intiated by EMS at the scene. From a public health standpoint, these studies are significant because they will assess whether breathing high-flow oxygen, a potentially simple, practical, widely accessible, portable, and cost-effective therapy, can improve stroke outcomes either independently or by extending the time window for IV tPA.

在正常大气压下呼吸高流量氧气（常压氧疗，NBO）可能是一种 维持缺血脑组织（"争取时间"）直至自发或治疗性再灌注的简单策略 发生，从而改善中风结果。通过防止早期缺血性细胞死亡，NBO可能是一种有用的方法 延长IV组织纤溶酶原激活剂（tPA）狭窄（3小时）时间窗的连续治疗 疗法我们最近的啮齿动物和飞行员人类中风研究提供了令人信服的证据， 赋予有效的神经保护作用。虽然这种好处似乎是短暂的，但与先前观察到的情况类似， 高压氧研究表明，如果NBO治疗的缺血组织后来再灌注，确实会产生持续的益处。 在这项提案中（Spotrias项目1），我们的目标是在一个双盲，随机， 安慰剂对照临床试验，招募了240名急性（<9小时）缺血性卒中患者，为期5年。患者 将接受NBO或Room Air治疗8小时，并接受一系列临床评估和CT扫描。 将在NIHSS变化的"意向治疗"统计分析中评估NBO的治疗潜力 治疗期间的分数。将在患者中评估NBO与再灌注的潜在协同益处 作为项目2（Lev）的一部分，接受基线和24小时CT灌注扫描以评估再灌注。 其他次要分析将包括评估治疗后临床功能评分、脑功能评分和脑功能评分。 出血率和CT扫描上的病灶体积增长。在第1年，我们将排除tPA治疗的患者， 研究NBO与tPA组合在栓塞（基于凝块的）啮齿动物中风模型中的安全性和效用。如果 联合治疗在啮齿类动物中似乎是安全的，如果第一年的人类数据没有引起安全性问题， 将在NBO的临床试验中纳入tPA治疗的患者。从这些研究中，我们希望收集初步的 数据和获得试点经验，为未来的多中心试验NBO启动EMS在现场。 从公共卫生的角度来看，这些研究意义重大，因为它们将评估呼吸是否 高流量氧气是一种潜在简单、实用、可广泛获得、便携且具有成本效益的疗法， 单独或通过延长IV tPA的时间窗改善卒中结局。