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（正常氧疗法，NBO）下呼吸高流量的氧气可能是 维持缺血性脑组织（“购买时间”）的简单策略，直到自发或治疗性再灌注 发生，从而改善了中风的结果。通过预防早期缺血细胞死亡，NBO可能是有用的 扩展静脉纤溶酶原激活剂（TPA）的狭窄（3小时）时间窗口的辅助治疗 治疗。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，即早期NBO 赋予有效的神经保护作用。虽然收益似乎是短暂的，但类似于先前观察到的收益 高压氧研究，如果稍后再融合了NBO治疗的缺血组织，则会发生持续的益处。 在此提案（现场项目1）中，我们旨在将我们的初步工作扩展到双盲，随机， 安慰剂对照的临床试验在5年内招募了240个急性（<9小时）缺血性中风患者。患者 将接收NBO或房间空气8小时，并进行连续的clincial评估和CT扫描。 NBO的治疗潜力将进行评估，以“治疗NIHSS变化的统计分析”的“目的” 治疗过程中的分数。 NBO通过再灌注的潜在协同益处将在患者中得到评估 作为项目2（LEV）的一部分，他接受了基线和24小时的CT-Perfusion扫描以评估再灌注。 其他二次分析将包括对疗法后临床功能评分的评估，大脑 CT扫描的出血率和病变量的增长。在第1年，我们将排除经过TPA治疗的患者和 研究NBO与TPA合并在栓塞（基于凝块）啮齿动物中风模型中的安全性和实用性。如果 联合疗法在啮齿动物中似乎是安全的，如果1年的人类数据没有引起安全问题，我们 将在NBO的临床试验中包括经过TPA治疗的患者。从这些研究中，我们希望收集初步 数据和获得试点经验，用于EMS在现场进行的NBO的未来多中心试验。 从公共卫生的角度来看，这些研究很重要，因为它们将评估呼吸是否 高流量氧，一种潜在的简单，实用，可访问，便携式和具有成本效益的疗法，可以 通过独立或扩展IV TPA的时间窗口来改善中风结果。