Rapid and Effective Localized Neurovascular Cooling Using the Khione Insulative Catheter

使用 Khione 绝缘导管快速有效的局部神经血管冷却

• 批准号: 9908759
• 负责人: THOMAS L MERRILL
• 金额: $ 96.75万
• 依托单位: FOCALCOOL, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908759
• 关键词: Acute; Address; Adult; Air; Animals; Behavior assessment; Blood flow; Brain; Caliber; Canis familiaris; Caring; Catheters; Cause of Death; Cessation of life; Clinical; Clinical Trials; Conflict (Psychology); Devices; Edema; Effectiveness; Freezing; Goals; Hemodilution; Hour; Industry; Infarction; Ischemic Stroke; Length; Letters; Mechanics; Methods; Modeling; Nanostructures; National Heart, Lung, and Blood Institute; Neurologic; Neurological outcome; Neuroprotective Agents; Outcome; Patient-Focused Outcomes; Patients; Performance; Phase; Pre-Clinical Model; Procedures; Production; Randomized Controlled Trials; Reperfusion Injury; Reperfusion Therapy; Research; Risk; Safety; Saline; Sample Size; Science; Solid; Stents; Sterility; Stroke; Structure; Temperature; Testing; Therapeutic; Thrombectomy; Tissues; Torque; Translating; United States; Vasospasm; Vendor; Work; base; blood perfusion; brain tissue; clinical care; clinical translation; clinically relevant; commercialization; cost; design; disability; efficacy testing; first-in-human; improved; improved outcome; in vivo evaluation; manufacturability; meetings; natural hypothermia; neuroprotection; neurovascular; phase 2 testing; preclinical efficacy; preclinical study; restoration; side effect; standard of care; stroke model; stroke patient; stroke therapy; technological innovation

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.

项目摘要 在美国，中风是第五大死亡原因，也是导致成人残疾的第一大原因。这个 急性缺血性中风(AIS)治疗的首要目标是迅速恢复血液灌流。然而，研究表明 已经表明，这种血流的回流虽然必要，但也会对局部组织造成损害，从而导致 病人的预后很差。治疗性低温(TH)已被证明是一种强有力的神经保护剂 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和机械相结合来改善AIS患者的预后 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 具有良好绝缘性的治疗性低温导管用于快速局部冷却缺血组织 风险。我们的第一阶段工作证明了降温效果的可行性以及脑组织挽救和神经学 在犬类中风模型中受益。第二阶段AIMS将确认犬只的安全性和组织挽救结果 模型，并使KHHONE™导管大大接近商业化。 具体目标：1)使用FDA提交前的指导意见和热设计要求表明 Khione™导管a)符合fda无菌和一次性使用的血管内导管标准，b)已准备就绪。 以进行更广泛的临床前疗效测试。2)以更大的统计信心展示khione™ 导管在临床相关犬卒中模型中的治疗潜力。FocalCool将把 科恩™导尿管设计成生产方法和程序。通过ISO/GMP认证的供应商将 制造用于设备测试的导管，以评估结构、安全和热性能。最后， Khione™导管的治疗效益将在适当功率的犬类研究中进行评估。 相关性：使用当今的MT设备(如支架取回器)进行有效的再通是一种很有前途的新方法 缺血性中风的标准护理。然而，再通后的再灌注损伤仍然是一种 缺血性卒中护理中未解决的问题。约50%的支架取回器患者带着改良的支架离开 Rankin评分大于3，表示中度残疾到重度残疾，包括死亡。这个 卒中治疗方法相结合的技术创新--机械取栓与精确井 综合再灌注低温-可能产生协同效益，从而减少梗塞面积和 改善长期神经预后。