Rapid and Effective Localized Neurovascular Cooling Using the Khione Insulative Catheter

项目摘要 中风是美国第五大死亡原因和成人残疾的头号原因。的 急性缺血性中风（AIS）治疗的主要目标是快速恢复血液灌注。然而研究 已经表明，这种血流的返回虽然是必要的，但也会对局部组织造成损伤，导致 患者预后差。治疗性低温（TH）已被证明是一种强大的神经保护剂， 临床前研究，但尚未转化为临床护理。 本研究的总体目标是通过将TH与机械治疗相结合来改善AIS患者的结局。 血栓切除术（MT）作为一种神经保护策略。FocalCool的产品Khione™导管是一种 具有上级绝缘的低温治疗导管，用于快速和局部冷却缺血组织， 风险我们的第一阶段工作证明了冷却的有效性、可行性和脑组织挽救以及神经系统功能。 在犬中风模型中的益处。第二阶段的目标是确认犬的安全性和组织挽救结果 Khione™导管的模型，使其更接近商业化。 具体目标：1）使用FDA预提交指南和热设计要求表明， Khione™导管a）符合FDA关于无菌和一次性血管内导管的标准，B） 进行更广泛的临床前疗效测试。2)以更高的统计置信度展示Khione™ 导管在临床相关犬卒中模型中的治疗潜力。FocalCool将传输 Khione™导管设计融入生产方法和程序。ISO / GMP认证的供应商将 制造用于器械测试的导管，以评估结构、安全性和热性能。最后 Khione™导管的治疗受益将在适当功率的犬研究中进行评价。 相关性：使用当今的MT器械（如支架取栓器）进行有效再通是一种很有前途的新方法， 缺血性中风的标准治疗然而，再通后的再灌注损伤仍然是一个重要因素。 缺血性中风护理中未解决的问题。大约50%的支架取栓装置患者离开时， 兰金评分大于3分，表明中度残疾至重度残疾，包括死亡。的 结合中风治疗疗法的技术创新-机械血栓切除术和精确井， 综合再灌注低温-可能产生协同效益，导致梗死面积减少， 改善长期的神经系统结果。

Project Summary Stroke is the 5th leading cause of death and number one cause of adult disability in the United States. The primary goal of acute ischemic stroke (AIS) treatment is quickly restoring blood perfusion. However, studies have shown that this return of blood flow, while necessary, can also cause damage to local tissue leading to poor patient outcomes. Therapeutic hypothermia (TH) has been shown to be a robust neuroprotectant in preclinical studies, but has not been translated to clinical care. The overall goal of this research is to improve AIS patient outcomes by combining TH with mechanical thrombectomy (MT) as a neuroprotective strategy. FocalCool’s product, the Khione™ Catheter, is a therapeutic hypothermia catheter with superior insulation used to rapidly and locally cool ischemic tissue at risk. Our Phase I work demonstrated cooling effectiveness feasibility and brain tissue salvage and neurological benefit in a canine stroke model. Phase II aims will confirm safety and tissue salvage results in the canine model and take the Khione™ Catheter significantly closer to commercialization. Specific Aims: 1) Using FDA pre-submission guidance and thermal design requirements show that the Khione™ Catheter a) meets FDA standards for sterile and single-use intravascular catheters and b) is ready for more extensive pre-clinical efficacy testing. 2) Demonstrate with greater statistical confidence Khione™ Catheter’s therapeutic potential in a clinically relevant canine stroke model. FocalCool will transfer the Khione™ Catheter design into production methods and procedures. An ISO / GMP certified vendor will manufacture catheters for device testing to assess structural, safety, and thermal performance. Finally, the therapeutic benefit of the Khione™ Catheter will be evaluated in an appropriately powered canine study. Relevance: Effective recanalization with today’s MT devices such as stent retrievers is a promising new standard of care for ischemic strokes. Reperfusion injury however, following recanalization continues to be an unmet problem in ischemic stroke care. Approximately 50% of stent retriever patients leave with modified Rankin Scores greater than 3, indicating moderate disability to severe disability, including death. The technological innovation of combining stroke treatment therapies – mechanical thrombectomy and precise well- integrated reperfusion hypothermia – may yield synergistic benefits, resulting in reduced infarct size and improved long-term neurological outcomes.