Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revasculariza

急性脑卒中低体温与血运重建的溶栓影像学评估

• 批准号: 8401815
• 负责人: DAVID SIGMUND LIEBESKIND
• 金额: $ 57.61万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8401815
• 关键词: Acute; Address; Adult; Advanced Development; Alteplase; Ancillary Study; Angiography; Arteries; Benchmarking; Biological Markers; Biology; Blood - brain barrier anatomy; Blood flow; Brain; Clinical; Clinical Trials; Confounding Factors (Epidemiology); Data; Development; Enrollment; Ensure; Evaluation; Functional disorder; Funding; Future; Goals; Growth; Health; Hemorrhage; Hour; Human; Image; Image Analysis; Imaging Device; Imaging Techniques; Infarction; Injury; Intravenous; Investigation; Investments; Ischemic Stroke; Knowledge; Laboratories; Leadership; Lesion; Magnetic Resonance Imaging; Measures; Middle Cerebral Artery Infarction; Myocardial Infarction; Neurological outcome; Outcome; Outcome Measure; Parents; Patients; Perfusion; Permeability; Phase; Population; Process; Property; Public Health; Relative (related person); Reperfusion Therapy; Research; Research Infrastructure; Research Personnel; Safety; Site; Stroke; Testing; Therapeutic; Time; Translations; United States National Institutes of Health; acute stroke; arm; base; disability; experience; improved; innovation; insight; middle cerebral artery; natural hypothermia; nervous system disorder; neuroprotection; pre-clinical; prospective; response; restoration; socioeconomics; success; thrombolysis

DESCRIPTION (provided by applicant): Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revascularization (HASTIER) is a focused ancillary imaging study to the Intravascular Cooling in the Treatment of Stroke 2 (ICTuS 2) trial, an ongoing, NIH-funded project on the safety and efficacy of hypothermia combined with thrombolysis. The objective of HASTIER is to address established preclinical concerns that hypothermia impairs recanalization and reperfusion with standard thrombolytic treatment with intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke in humans. Our hypothesis is that hypothermia does not impair either recanalization (opening of the artery) or reperfusion (restoration of downstream flow) with thrombolysis. This prospective, ancillary study of 120 ICTuS 2 subjects with middle cerebral artery stroke over 2 years uses an innovative imaging approach with multimodal CT/MRI to seamlessly evaluate these distinct aspects of revascularization. The relative impact of recanalization (CTA/MRA from baseline to 36 hours in Specific Aim 1) and reperfusion (CT/MR perfusion from baseline to 36 hours and imaging correlates of reperfusion such as hemorrhage and infarct growth in Specific Aim 2) may be impossible to predict or decipher without imaging as proposed in this study. Hypothermia and thrombolysis each offer potential benefit to improve stroke outcome, yet the concern regarding impaired thrombolysis during hypothermia may impede further translation. HASTIER uses an experienced core lab and expertise from landmark stroke imaging trials to test hypothermic thrombolysis against established revascularization benchmarks. HASTIER outcomes in Specific Aims 1 and 2 will provide distinct, yet complementary data essential to future development of combined hypothermia and thrombolysis with IV tPA. HASTIER imaging outcomes for recanalization and reperfusion may be extremely valuable irrespective of ICTuS 2 results, identifying the mechanisms that drive neurological outcomes and advancing other studies of revascularization beyond hypothermic thrombolysis. The expertise and infrastructure for this short, focused study of concrete scientific objectives will enhance the NIH investment in ICTuS 2, expanding knowledge on revascularization for acute stroke in humans and the impact of hypothermia. PUBLIC HEALTH RELEVANCE: Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revascularization (HASTIER) is an ancillary imaging study to the Intravascular Cooling in the Treatment of Stroke 2 (ICTuS 2) trial, an ongoing NIH-funded project on the safety and efficacy of hypothermia combined with thrombolysis. Understanding the beneficial effects and potential concerns of this combination treatment to open arteries and restore blood flow in stroke, the leading cause of adult disability in the US, is a key priority for improving pulic health. Imaging evaluation of revascularization will advance development of this combined approach and prominently impact other stroke treatments.

描述（由申请人提供）：急性中风中的低体温与溶栓成像血运重建评估 (HASTIER) 是针对血管内冷却治疗中风 2 (ICTuS 2) 试验的一项重点辅助成像研究，该试验是一项由 NIH 资助的正在进行的项目低温联合溶栓的安全性和有效性。 HASTIER 的目标是通过使用静脉内 (IV) 组织纤溶酶原激活剂 (tPA) 进行标准溶栓治疗治疗人类急性缺血性中风，解决临床前已知的低温会损害再通和再灌注的问题。我们的假设是，体温过低不会损害溶栓治疗的再通（动脉的开放）或再灌注（下游血流的恢复）。这项前瞻性辅助研究对 120 名患有大脑中动脉卒中的 2 年以上受试者进行了前瞻性辅助研究，使用创新的多模态 CT/MRI 成像方法来无缝评估血运重建的这些不同方面。再通（特定目标 1 中从基线到 36 小时的 CTA/MRA）和再灌注（特定目标 2 中从基线到 36 小时的 CT/MR 灌注以及再灌注的影像学相关性，例如出血和梗塞生长）的相对影响可能是不可能的按照本研究中的建议，无需成像即可预测或破译。低温和溶栓均可以改善中风结局，但对低温期间溶栓受损的担忧可能会阻碍进一步转化。 HASTIER 利用经验丰富的核心实验室和具有里程碑意义的中风成像试验的专业知识，根据既定的血运重建基准测试低温溶栓。具体目标 1 和 2 中的 HASTIER 结果将为未来开发静脉注射 tPA 联合低温和溶栓治疗提供重要的独特但补充的数据。无论 ICTuS 2 结果如何，HASTIER 的再通和再灌注成像结果可能都非常有价值，它可以确定驱动神经系统结果的机制，并推进除低温溶栓之外的血运重建的其他研究。这项针对具体科学目标的简短、重点研究的专业知识和基础设施将增强 NIH 对 ICTuS 2 的投资，扩大对人类急性中风血运重建和体温过低影响的了解。 公共健康相关性：急性中风中的低体温与溶栓成像血运重建评估 (HASTIER) 是血管内冷却治疗中风 2 (ICTuS 2) 试验的一项辅助成像研究，该试验是 NIH 资助的一项正在进行的关于安全性和有效性的项目低温联合溶栓。了解这种联合治疗对开放动脉和恢复中风血流的有益效果和潜在问题是改善公众健康的首要任务，中风是美国成人残疾的主要原因。血运重建的影像学评估将促进这种组合方法的发展，并对其他中风治疗产生显着影响。