Iridium-electrode inhaled Nitric Oxide generator for treatment of hypoxic respiratory failure in neonates

摘要 我们建议在现有临床的基础上开发一种医疗设备 从空气中产生医用级一氧化氮(NO)以供吸入的原型。 一种Ir电极吸入NO发生器将取代现有的装置，该装置 利用无气瓶供应链和复杂的床边管理系统， 并极大地增加了全球范围内获得这一救命儿科选择性 肺血管扩张剂。 吸入NO引起肺血管扩张，而不是全身性 血管扩张，这是目前其他可用的治疗方法的一个重要问题。 1999年12月，美国食品和药物管理局(FDA)批准 吸入NO治疗足月儿或近月儿缺氧 呼吸衰竭(HRF)以来，吸入NO一直是救命稻草 对住院婴幼儿急性肺动脉高压的干预。 我们在麻省理工学院Zapol实验室的合作者最近报告了一项数据 从测试110V交流供电床边NO发电装置获得 建立羔羊肺动脉高压(PAH)模型。这个原型是 随后在6名健康患者中进行了人类概念验证(POC)试验 志愿者和迄今在MGH导尿室接受治疗的5名PAH患者。第三 POL和Zapol实验室已经在NHLBI B-BIC/NCAI赠款下开始工作 #U54HL119145，用于优化NO发生器的电极设计 机械呼吸机和麻醉机。 我们将与专业临床医生一起开发一种Ir电极NO发生器。 在FDA设计控制下的输入将作为临床的基础 生物等效性研究预计需要获得监管部门的批准。 在学术背景下的发展尚未在正式的 FDA设计控制，这是获得IDE状态和进入更广泛领域的要求 临床试验。用最优材料制成的吸入NO发生器的Ir电极 设计将在全球范围内为婴儿提供NO吸入疗法 使用人力资源管理局。

Abstract We propose to develop a medical device building on an existing clinical prototype that generates medical grade nitric oxide (NO) from air for inhalation. An iridium-electrode inhaled NO generator will supersede existing devices which utilize NO cylinder supply chains and complex bedside administration systems, and vastly increase worldwide access to this lifesaving pediatric selective pulmonary vasodilator. Inhaled NO produces pulmonary vasodilation without systemic vasodilation, which is a significant issue with other currently available therapies. In December 1999, the US Food and Drug Administration (FDA), approved inhaled NO for the treatment of hypoxic term or near-term infants with hypoxic respiratory failure (HRF) since which time inhaled NO has been a life-saving intervention for hospitalized infants to treat acute pulmonary hypertension. Our collaborators in the Zapol lab at MGH recently reported on data obtained from testing a 110V AC-powered bedside NO generating device in a lamb model of pulmonary artery hypertension (PAH). This prototype was subsequently tested in a human proof of concept (POC) trial in 6 healthy volunteers and to date 5 patients with PAH in the MGH catheterization lab. Third Pole and the Zapol lab have commenced work under NHLBI B-BIC/NCAI grant #U54HL119145 to optimize the electrode design of an NO generator for use with mechanical ventilators and anesthesia machines. We will develop an iridium-electrode NO generator with expert clinician input under FDA design controls which will serve as a basis for clinical bioequivalence studies anticipated to be required for regulatory approval. Development in the academic setting has not yet been conducted under formal FDA design controls, a requirement for obtaining IDE status and entering broader clinical trials. An iridium-electrode inhaled NO generator, with optimal materials and design will enable worldwide provision of NO inhalation therapy for infants with HRF.