Rapid and Effective Localized Neurovascular Cooling Using the Khione Insulative Catheter

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.Project Narrative Stroke is the 5th leading cause of death and a leading cause of disability in the United States. For stroke treatment, quickly restoring blood flow has been shown to improve outcome; yet some experts have found reperfusion injury reduces these benefits. FocalCool, LLC seeks to develop and achieve regulatory approval of a therapeutic hypothermia catheter used in conjunction with endovascular stent retriever devices, to maximize the benefit of blood flow restoration while minimizing the damaging effects of reperfusion injury.