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.
Public Health Relevance Statement: Narrative Nitric Oxide is a selective pulmonary vasodilator that was approved in 1999 in the US to treat neonates that are born blue - with Hypoxic Respiratory Failure. The therapy remains expensive and difficult to use. Third Pole is developing technology to make Nitric Oxide from air- enabling access to the medicine worldwide.
Project Terms: abstracting; Acute; Adult; Air; American; Anesthesia procedures; Animals; base; Breathing; Catheterization; Childhood; Clinical; Clinical Research; Clinical Trials; Complex; Computer software; cost; Custom; Data; design; Development; Devices; electric impedance; Electrodes; Ensure; Etiology; experience; Factor Analysis; Gases; General Hospitals; Goals; Grant; healthy volunteer; Heart failure; Hospitals; Human; Hypoxia; Infant; Inhalation Therapy; inhaled nitric oxide; Intervention; Interview; Iridium; Laboratories; Life; Literature; Lung; Maps; Marketing; Massachusetts; Mechanical Ventilators; Medical; Medical Device; Medicine; Modeling; Monitor; National Heart, Lung, and Blood Institute; Neonatal Intensive Care Units; neonate; Nitric Oxide; Nitrogen Dioxide; novel; Oxygen; particle; Patients; Penetration; Phase; Price; Probability; programs; prototype; pulmonary arterial hypertension; Pulmonary Hypertension; Readiness; Reporting; Research; respiratory; Respiratory Failure; Safety; safety testing; sensor; Series; Small Business Innovation Research Grant; success; System; Technology; Testing; Therapeutic Equivalency; Time; United States Food and Drug Administration; uptake; usability; user-friendly; Vasodilation; Vasodilator Agents; Visit; Work
