A Naloxone Parachute: Novel Wearable Dual-Sensor Regional Oximeter to Detect Opioid-Induced Hypoxia and Enable Emergent Naloxone Rescue

纳洛酮降落伞：新型可穿戴双传感器区域血氧计，用于检测阿片类药物引起的缺氧并实现紧急纳洛酮救援

• 批准号: 10612485
• 负责人: Desislava Zlatanova Hite
• 金额: $ 96.4万
• 依托单位: AYUDA MEDICAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612485
• 关键词: 911 call; Accidents; Acute; Adverse effects; Algorithms; Biosensor; Blood gas; Bluetooth; Body Weight; Breakthrough device; Cardiopulmonary Resuscitation; Certification; Charge; Chronic; Clinical; Clinical Research; Collaborations; Communication; Communities; Data; Data Analyses; Dedications; Development; Device Designs; Device Safety; Device or Instrument Development; Devices; Diagnostic Equipment; Distress; Drops; Early Diagnosis; Effectiveness; Emergency Situation; Engineering; Enrollment; Environment; Environmental Monitoring; Evaluation; Event; Exanthema; Fatality rate; Feasibility Studies; Formularies; Gases; Goals; Hearing; Home; Hour; Human; Hypoxia; Ingestion; Innovation Corps; Instruction; Intervention; Intravenous; Intuition; Label; Learning; Life; Light; Location; Logic; Longevity; Low Income Population; Marketing; Measures; Mediating; Medicaid; Medical; Medical emergency; Monitor; Motion; Naloxone; National Institute of Drug Abuse; Neighborhood Health Center; Opioid; Output; Parachuting; Patients; Performance; Persons; Phase; Physiologic Monitoring; Physiologic pulse; Physiological; Pilot Projects; Population; Populations at Risk; Probability; Protocols documentation; Recording of previous events; Reporting; Research Design; Research Personnel; Resolution; Respiration; Resuscitation; Risk; Safety; Signal Transduction; Sleep; Small Business Innovation Research Grant; Speed; Sunlight; System; Target Populations; Telephone; Testing; Time; Tourniquets; United States Food and Drug Administration; United States Substance Abuse and Mental Health Services Administration; Upper arm; Vision; Voice; arm; chronic pain; clinical diagnostics; cloud based; commercialization; communication device; data exchange; design; handheld mobile device; impression; improved; loved ones; mobile application; mobile medical application; novel; opioid overdose; opioid use; opioid use disorder; opioid user; patient safety; pressure; prevent; remifentanil; response; sensor; side effect; standard of care; stressor; success; transmission process; verbal; wearable device; wireless

SBIR PHASE II - ABSTRACT Ayuda Medical has the vision that no-one should die from a treatable medical emergency. Opioid overdoses (OODs) are treatable with basic CardioPulmonary Resuscitation (CPR), but they claimed over 250 lives each day in the US in 2020. Patients most at risk for OOD are people in treatment for Opioid Use Disorder (OUD) or High Impact Chronic Pain (HICP). The current standard of care to OOD is bystander response (medical or nonmedical), but the bystander needs to know that an OOD is occurring. We present a wearable medical diagnostic device to detect OOD and bridge the gap to bystander intervention. Our device, Parachute ARMband, will be worn continuously, and will monitor physiologic parameters that indicate OOD, then will use an on-device escalating tonal alarm to summon bystanders, as well as on- device speaker to verbally identify the urgency to get medical help. No wireless connectivity is required for these functions. The ARMband will also send a Bluetooth alert to an adjunct Mobile Medical Application (MMA) on the User’s phone, that can reach designated contacts, previously chosen by the device user. This function requires mobile device connectivity, and that the MMA be downloaded prior to the medical event. Company has completed a Phase I SBIR, sponsored by National Institute of Drug Abuse (NIDA), that showed the upper arm is a viable location for wearable oximeters, main components of novel device. The addition of Phase I Innovation Corps enabled company to validate Minimal Viable Product (MVP) key features, including escalating alarm and wireless alert. Together our Phase I learnings allowed Principle Investigator (PI) to submit a Breakthrough Device Designation (BDD) request to the FDA. This proposed Phase II application will show feasibility of our novel device components to detect gas- induced hypoxia, compared to arterial blood gas (Aim 1); sensitivity of device to detect intravenous remifentanil “OOD” and begin alarm algorithm (Aim 2); and ability of device communications to send a real-time wireless alert (Aim 3). These three aims support device safety and effectiveness. In Aim 4, Human Factors and Instructions for Use (IFU) are specifically tested in our target population, persons with a history of OUD or OOD. Aim 5 likewise tests the device in our target population, but also adds our target use environment; it will test device’s wearability via 48hr and and two-to-four week take home studies. Together all five Aims, along with non-clinical testing of device design and alarms, will support seeking Class II marketing via a De Novo submission, with the device indicated for People Who Use Opioids (PWUOs) including HICP, and people with a history of OUD that are at risk for OOD. To date there is no FDA approved device to monitor for OOD. We offer a continuous monitor because stressors and triggers to opioid use can be unexpected. The De Novo submission will include data from studies designed for our target clinical scenario (acute opioid ingestion/ administration), and target use environment (ambulatory, at-home). Ayuda Medical plans to have several discussions with the United States Food and Drug Administration (FDA), throughout device development and Phase II. BDD was submitted in Q3, 2021, and company plans to submit a Q-sub clarifying our milestones to approval in Q4, 2021. We plan to use early gas hypoxia studies (Aim 1A) to apply for Investigational Device Exemption (IDE), and then perform clinical studies with opioid- specific protocols (Aims 2 and 3). This includes feasibility (Q4, 2022) and pivotal (Q4, 2023) studies sponsored by Phase II. Continuous interactions with FDA will align company milestones with FDA objectives. Commercialization strategy includes seeking federal Medicaid coverage in tandem with FDA approval, as part of a dual-panel (FDA-CMS) pre-marketing review. Company plans to market the ARMband directly within the OUD market, and co-market the device with a strategic partner within the HICP market. We also intend to conduct community-based pilot studies in collaboration with NIDA and the Substance Abuse and Mental Health Services Administration (SAMHSA), to validate device system in specific to the OUD/HICP populations in target environment, and to support formulary inclusion by State Medicaid. State Medicaid coverage assures that the device is affordable and accessible by Community Health Centers (CHCs), that treat the majority of the low-income populations for both chronic and acute illnesses, including OUD and OOD. Establishing a viable commercial path via state Medicaid and CHCs, that can then be expanded into 50 states, is an attractive proposal to partnerships and potential exit companies in the OUD market. Phase I validated device need and feasibility of our development approach. Phase II will provide the appropriate clinical and non-clinical testing to support a De Novo submission to the FDA. Company is fully dedicated to the approval and commercialization of the Parachute ARMband OOD diagnostic device, and to making it available to all at-risk groups, aiming to expand the protection against accidental opioid overdose.

SBIR II期 - 摘要 Ayuda Medical的愿景是，没有人应该死于可治疗的医疗紧急情况。阿片类药物 过量剂量（OOD）可以用基本的心肺复苏（CPR）治疗，但他们声称超过250 2020年美国每天生活。 疾病（OUD）或高冲击慢性疼痛（HICP）。当前对OOD的护理标准是旁观者 反应（医学或非医学），但是旁观者需要知道正在发生OOD。我们提出一个 可穿戴的医疗诊断装置，以检测OOD并弥合差距到旁观者干预。 我们的设备降落伞臂章将连续磨损，并将监视生理参数 这表明OOD，然后将使用磁场升级的音调警报来召唤旁观者，以及 设备扬声器以口头确定获得医疗帮助的紧迫性。不需要无线连接 这些功能。臂章还将向辅助移动医疗应用发送蓝牙警报 （MMA）在用户手机上，该手机可以接触到设备用户以前选择的指定联系人。这 功能需要移动设备连接，并在医疗事件之前下载MMA。 公司已经完成了由美国国家药物滥用研究所（NIDA）赞助的I期SBIR，该公司已完成 显示上臂是可穿戴氧化剂的可行位置，这是新设备的主要组成部分。 I阶段创新团的增加使公司能够验证最小可行产品（MVP）关键功能， 包括升级警报和无线警报。我们的阶段我学到的阶段允许主要调查员 （PI）向FDA提交突破设备名称（BDD）请求。 该拟议的II期应用将显示我们新型设备组件检测气体的可行性 - 与动脉血气相比，诱发缺氧（AIM 1）；设备检测静脉雷曲霉的敏感性 “ OOD”并开始警报算法（AIM 2）；设备通信发送实时无线的能力和能力 警报（目标3）。这三个目的支持设备的安全性和有效性。在AIM 4中，人为因素和 使用（IFU）的说明在我们的目标人群中进行了专门测试， ood。 AIM 5同样在目标人群中测试该设备，但也增加了我们的目标使用环境；会 测试设备通过48小时和两到四周的可穿戴能力进行回家研究。 所有五个目标一起，以及对设备设计和警报的非临床测试都将支持寻求 通过从头提交的II类营销，该设备为使用阿片类药物的人（PWUOS）指示 包括HICP，以及有OD风险的OUD历史的人。迄今为止，尚未获得FDA批准 监视OOD的设备。我们提供连续监视 意外。从头提交的提交将包括为我们的目标临床方案设计的研究的数据 （急性阿片类药物摄入/给药）和目标使用环境（卧床，在家）。 Ayuda医疗计划与美国食品药品监督管理局进行多次讨论 （FDA），整个设备开发和II期。 BDD于2021年第三季度提交，公司计划 提交Q-Sub澄清我们的里程碑颁发在2021年第四季度的批准。我们计划使用早期气体缺氧研究 （AIM 1A）申请研究设备的豁免（IDE），然后使用阿片类药物进行临床研究 特定协议（目标2和3）。这包括可行性（第4季度，2022年）和关键（Q4，2023）研究 由II期赞助。与FDA的持续互动将使公司里程碑与FDA目标保持一致。 商业化策略包括寻求联邦医疗补助与FDA批准同时覆盖， 作为双面板（FDA-CMS）的一部分。公司计划直接推销臂章 在Oud市场中，并与HICP市场中的战略合作伙伴共同市场。我们也是 打算与NIDA以及滥用药物以及 精神卫生服务管理局（SAMHSA），以特定于OUD/HICP验证设备系统 目标环境中的种群，并支持国家医疗补助的配方。 覆盖范围确保该设备可以通过社区卫生中心（CHC）来负担得起且可以使用 包括OUD和OOD在内的慢性疾病和急性疾病的大多数低收入人群。 通过州医疗补助和CHC建立可行的商业路径，然后可以将其扩展到50个州， 是对Oud市场中合作伙伴关系和潜在退出公司的有吸引力的建议。 第一阶段验证了我们开发方法的设备需求和可行性。第二阶段将提供 适当的临床和非临床测试，以支持从头提交FDA。公司完全 致力于批准和商业化降落伞臂章OOD诊断设备，并 将其提供给所有高危人群，旨在扩大针对意外的阿片类药物过量的保护。