Prapela proposes to complete the development of and then establish the safety, efficacy, and clinical risk/benefit of a novel hospital incubator pad that will provide a complementary treatment and the first improvement in the clinical management of apnea of prematurity (AOP) in over 20 years. Defined as cessation of breathing for 20 seconds or longer or a shorter pause accompanied by hypoxemia, AOP is a major morbidity among preterm infants and a significant healthcare burden. AOP affects 70% of all early preterm births (<34 weeks gestational age) and nearly all at ⤠28 weeks' gestation. In the United States in 2020, the total annual direct costs associated with AOP exceeded $12 billion. While there is no consensus for treating AOP, common interventions include positional techniques, caffeine citrate, manual tactile stimulation, and supplemental oxygen for hypoxemia. Caffeine citrate is the first line of therapy as it decreases apneic episodes and reduces the need for assisted ventilation. At recommended doses, caffeine has been proven safe and effective. However, in the sole trial supporting its FDA clearance, a majority of newborns treated with caffeine citrate continued to experience apnea events. In 2015, a clinical study using a stochastic vibrotactile stimulation (SVS) investigational device reported a 50% reduction in the number of apnea events. Prapela exclusively licensed the SVS technology of the investigational device and has demonstrated technical feasibility replicating the clinically critical stimulation in prototype incubator pads. The broad objective of this SBIR Fast-Track application is to generate the data and documentation necessary for FDA marketing clearance of a novel device to reduce apnea events in preterm newborns. To accomplish this objective, Prapela proposes four Specific Aims: 1) complete development of the SVS incubator pad, 2) demonstrate the safety of the device, 3) determine the clinical efficacy of the SVS incubator pad as an adjunctive therapy to concurrent pharmacological treatment in newborns with AOP, and 4) document the benefit-risk assessment of the device from clinicians caring for AOP patients. Efficacy will be established through a masked, randomized clinical trial with newborns of <33 weeks gestational age, with postmenstrual age (PMA) of <38 weeks at the time of enrollment. The control group will receive standard therapy only with caffeine citrate and respiratory support and an inert SVS device, while the intervention group will receive standard therapy concurrent with the Prapela SVS device. The primary outcome measure will be the mean number of apnea events in the three days after study entry, with a reduction in apnea events of 30% or more considered clinically significant. Questionnaires administered at the end of each experimental period to the clinicians present on the final shift will capture the benefit-risk assessment. The successful completion of the project will provide the data and documentation necessary for FDA marketing clearance and commercialization of our SVS incubator pad as a purpose-built device to improve clinical outcomes of preterm infants with AOP.
Public Health Relevance Statement: Preterm infants often have apnea, which consists of pauses in breathing associated with drops in heart rate and becoming blue or pale. This project will complete the development of and then establish the safety, efficacy, and clinical benefit of a hospital incubator pad with stochastic vibrotactile stimulation. The results of this project will provide for FDA clearance of a complementary, non-pharmacological treatment and the first improvement in the clinical management of newborns with apnea of prematurity in over twenty years.
Project Terms: Affect; ages; Age; Apnea; Breathing; Respiratory Aspiration; Respiratory Inspiration; inspiration; Caffeine; Citrates; Clinical Research; Clinical Study; Control Groups; Electromagnetics; Engineering; Future; Gestational Age; Chronologic Fetal Maturity; Fetal Age; Heart Rate; Cardiac Chronotropism; Hospitals; Human; Modern Man; Incubators; Infant; Infant Care; baby care; infant health care; infant healthcare; newborn care; Newborn Infant; 0-4 weeks old; Newborns; newborn child; newborn children; Premature Infant; infants born premature; infants born prematurely; premature baby; premature infant human; preterm baby; preterm infant; preterm infant human; Manuals; Marketing; Masks; Mattresses; Medical Device; Morbidity - disease rate; Morbidity; United States National Institutes of Health; NIH; National Institutes of Health; Patients; Pediatrics; Peer Review; Power Sources; Power Supplies; Pregnancy; Gestation; Publishing; Questionnaires; Recommendation; Reference Standards; Research; Risk; Safety; Software Validation; Software Verification; Technology; Testing; Theophylline; Constant T; ConstantT; Elixophyllin; LaBID; Respbid; Slo Phyllin; Slo-bid; SloPhyllin; Somophyllin T; Somophyllin-CRT; SomophyllinT; T-Phyl; Theo 24; Theo24; Theobid Duracap; Theochron; Uniphyl; Time; United States; health care; Healthcare; measurable outcome; outcome measurement; Outcome Measure; Caring; Prematurely delivering; Preterm Birth; premature childbirth; premature delivery; preterm delivery; Premature Birth; improved; CPAP; CPAP Ventilation; Continuous Positive Airway Pressure; Clinical; prematurity; premature; Phase; randomized, clinical trials; Licensing; randomized control trial; Randomized, Controlled Trials; Consensus; Dimensions; Frequencies; Event; Techniques; System; vibration; respiratory; Risk-Benefit Assessment; biomaterial compatibility; biocompatibility; experience; novel; Benefits and Risks; Devices; Reporting; Hypoxemia; hypoxemic; Positioning Attribute; Position; performance tests; Intervention; Intervention Strategies; interventional strategy; Documentation; Complementary therapies; Complementary treatment; Drops; Address; Dose; Data; Direct Costs; Regulatory Pathway; Clinical Management; Enrollment; enroll; Pharmacological Treatment; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Development; developmental; care burden; designing; design; clinical efficacy; determine efficacy; efficacy analysis; efficacy assessment; efficacy determination; efficacy examination; evaluate efficacy; examine efficacy; efficacy evaluation; intervention efficacy; therapeutic efficacy; therapy efficacy; Treatment Efficacy; Outcome; manufacturing plants; production plants; manufacturing facility; cost effective; clinical relevance; clinically relevant; clinical significance; clinically significant; inclusion criteria; prototype; commercialization; group intervention; primary outcome; standard of care; effective treatment; effective therapy; safety testing; clinical risk; premature neonates; premature newborn; preterm neonate; preterm newborn; vibrotactile stimulation; ventilation; tactile stimulation; supplemental oxygen; manufacturing cost; fabrication cost; Breakthrough device
