Flow Acceleration for Stroke Thrombolysis (FAST) System

中风溶栓 (FAST) 系统的流量加速

基本信息

批准号：
10572098
负责人：
Francis Milton Creighton
金额：
$ 3.41万
依托单位：
UNANDUP, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10572098
关键词：
Acceleration Acute Address Alteplase American Anterior Biological Blood Circulation Blood coagulation Cause of Death Cessation of life Coagulation Process Cytolysis Data Diagnosis Diffusion Dose Economic Burden FDA approved Feasibility Studies Fibrinolytic Agents Hemorrhage Hospitals Hour Infusion procedures Iron Ischemic Stroke Label Magnetism Mechanics Nature Neurologic Palliative Care Pathway interactions Patient Transfer Process Recovery Risk Safety Silicon Dioxide Stroke Surface System Technology Thrombectomy Time Travel Underserved Population United States acute care disability hemodynamics improved in vivo meetings nanoparticle nanoparticle delivery novel prevent standard of care stroke event stroke outcome stroke patient stroke therapy stroke victims thrombolysis tool

Acceleration Acute Address Alteplase American Anterior Biological Blood Circulation Blood coagulation Cause of Death Cessation of life Coagulation Process Cytolysis Data Diagnosis Diffusion Dose Economic Burden FDA approved Feasibility Studies Fibrinolytic Agents Hemorrhage Hospitals Hour Infusion procedures Iron Ischemic Stroke Label Magnetism Mechanics Nature Neurologic Palliative Care Pathway interactions Patient Transfer Process Recovery Risk Safety Silicon Dioxide Stroke Surface System Technology Thrombectomy Time Travel Underserved Population United States acute care disability hemodynamics improved in vivo meetings nanoparticle nanoparticle delivery novel prevent standard of care stroke event stroke outcome stroke patient stroke therapy stroke victims thrombolysis tool

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项目摘要

Acute ischemic stroke (AIS) results from a blood clot in the neurovasculature and is the 5th leading cause of death and 1st leading cause of neurological disability in the United States (US). AIS impacts more than 700,000 Americans annually, with a 65% chance of death or severe disability. By 2030, it is expected that the AIS economic burden will exceed $180B in the US alone. Standard of care AIS therapies include the use of the FDA approved thrombolytic agent alteplase (i.e., tissue plasminogen activator) within 4.5 hours of stroke onset and earliest-possible thrombectomy for large vessel occlusions (out to 24hrs). In contrast to thrombectomy, thrombolysis does not require confirmation of a vessel occlusion. Because only ~10% of AIS victims are eligible for thrombectomy, thrombolysis remains a critical first line tool to treat those diagnosed with AIS. When employed, thrombolysis is associated with a ~15% improvement in stroke outcomes with ~10% fully recovering. However, due to the ~7% dose-dependent associated hemorrhage rate of alteplase, thrombolysis is contraindicated for mild and wake-up strokes which together make up ~60% of all AIS events. Due to safety concerns and limited reliability, usage of thrombolysis in the US remains low (~10%) with 90% of all AIS victims receiving only palliative care. There remains an urgent need to improve first line use of thrombolysis which can be expanded to all AIS victims. UNandUP has invented a novel thrombolysis platform to safely accelerate alteplase to the obstructing blood clot, thereby overcoming the restrictive hemodynamics known to prevent alteplase from quickly reaching the occlusion. The proposed magnetic infusion platform overcomes this barrier by 1) adjunctively conveying alteplase to the clot’s surface more than 100X faster than normal biological diffusion (i.e., minutes vs. hours), and 2) mechanically mixing alteplase at the clot’s surface so that lysis is more reliable. Because alteplase is not conjugated and the mode of action is purely mechanical in nature, FDA meetings confirmed a CDRH IDE pathway is appropriate in support of an FDA Early Feasibility Study, which is a shorter and less expensive pathway compared to a CDER IND process. Importantly, the technology is affordable, does not require precise focusing, and can be configured to travel with patients transferred between hospitals for thrombectomy. Once proven safe and effective using current FDA approved alteplase labeling, UNandUP intends to expand thrombolysis to mild and wake up strokes by increasing the lysis efficacy of smaller alteplase doses known not to induce hemorrhage. If successful, thrombolysis could be safely extended to all 700,000 AIS victims for the first time, which is 10X more than currently treated. The project’s aims include 1) building the magnetic infusion subcomponents (magnetic workstation, silica coated iron nanoparticles, nanoparticle delivery system), and conducting 2) mechanism of action, 3) in vivo safety, and 4) clot interaction studies. Data obtained for the proposed effort will be critical to address FDA concerns in advance of an FDA Early Feasibility Study IDE.

急性缺血性中风（AIS）是由神经血管系统中的血块引起的，是第五个主要原因在美国的死亡和神经残疾的第一主要原因（美国）。 AIS影响超过700,000 美国人每年有65％的死亡或严重残疾。到2030年，预计AIS 仅在美国，经济燃烧就会超过$ 180B。 AIS疗法的护理标准包括使用FDA认可的溶栓剂Alteplase（即组织纤溶酶原激活剂）在中风发作的4.5小时内，最早可用于大型血栓切除术容器的闭塞（到24小时）。与血栓切除术相比，溶栓不需要确认容器阻塞。由于只有约10％的AIS受害者有资格进行血栓切除术，因此溶栓仍然是关键的一线工具可以治疗被诊断为AIS的人。使用时，溶栓分解与〜10％的中风结局提高了约15％，而完全恢复了约10％。但是，由于剂量依赖约7％相关的交替出血速率，溶栓是针对轻度和唤醒中风的禁用共同占所有AIS事件的约60％。由于安全问题和有限的可靠性，溶栓的使用情况在美国，所有仅接受姑息治疗的AIS受害者中有90％仍然很低（约10％）。仍然有一个迫切需要改善可以扩展到所有AIS受害者的溶栓的第一线使用。 UnAndup发明了一个新型的溶栓平台，可以安全加速替代阻塞血凝块，从而克服了已知的限制性血流动力学，以防止替代方案快速到达阻塞。提出的磁输液平台克服了此障碍1）辅助输送凝块表面的高度比正常生物扩散速度快100倍以上（即分钟与小时）， 2）在凝块表面机械混合高培酶，以使裂解更可靠。因为高速倍数是未连接，作用方式本质上是纯机械的，FDA会议证实了CDRH IDE 途径适合支持FDA早期可行性研究，这是一项较短且价格较低的与CDER过程相比，途径。重要的是，该技术负担得起，不需要精确聚焦，可以配置为与医院之间转移的患者进行血栓切除术。一次使用当前的FDA批准的变更平板标签证明安全有效，UnAndup打算扩展通过提高已知的较小替代剂量的裂解效率，溶血分析可轻度和唤醒中风诱导出血。如果成功的话，可以安全地将溶栓扩展到所有700,000 AIS滥用第一次，比目前治疗的多10倍。该项目的目的包括1）建立磁输注亚组件（磁性工作站，二氧化硅涂层的铁纳米颗粒，纳米颗粒输送系统）和进行2）作用机理，3）体内安全性和4）凝块相互作用研究。获得的数据在FDA早期可行性研究IDE之前，提出的努力对于解决FDA问题至关重要。