Prapela® SVS incubator pad: A cost-effective stochastic vibrotactile device to improve the clinical course of infants with apnea of prematurity.

Prapela建议完成一种新型医院保温箱垫的开发，然后确定其安全性、有效性和临床风险/受益，该保温箱垫将提供补充治疗，并在20多年来首次改善早产儿呼吸暂停（AOP）的临床管理。AOP定义为呼吸停止20秒或更长时间或更短的暂停，伴有低氧血症，是早产儿的主要发病率，也是显著的医疗负担。AOP影响70%的早期早产儿（胎龄<34周），几乎所有早产儿的胎龄≤ 28周。在美国，2020年与AOP相关的年度直接成本总额超过120亿美元。虽然对AOP的治疗没有共识，但常见的干预措施包括体位技术、柠檬酸咖啡因、手动触觉刺激和低氧血症的补充氧气。柠檬酸咖啡因是治疗的第一线，因为它减少了呼吸暂停发作，减少了对辅助通气的需求。在推荐剂量下，咖啡因已被证明是安全有效的。然而，在支持其FDA许可的唯一试验中，大多数接受柠檬酸咖啡因治疗的新生儿继续经历呼吸暂停事件。2015年，一项使用随机振动触觉刺激（SVS）试验用器械的临床研究报告称，呼吸暂停事件的数量减少了50%。Prapela独家许可了研究器械的SVS技术，并证明了在原型培养箱垫中复制临床关键刺激的技术可行性。该SBIR快速通道申请的广泛目标是生成FDA批准一种新型器械上市所需的数据和文件，以减少早产儿呼吸暂停事件。为了实现这一目标，Prapela提出了四个具体目标：1）完成SVS保温箱垫的开发，2）证明该器械的安全性，3）确定SVS保温箱垫作为AOP新生儿并发药物治疗的替代疗法的临床疗效，以及4）记录护理AOP患者的临床医生对该器械的获益-风险评估。疗效将通过一项盲法随机临床试验确定，试验对象为胎龄<33周的新生儿，入组时经后年龄（PMA）<38周。对照组将仅接受标准治疗，包括柠檬酸咖啡因、呼吸支持和惰性SVS装置，而干预组将接受标准治疗，同时使用Prapela SVS装置。主要结局指标是进入研究后3天内呼吸暂停事件的平均数量，呼吸暂停事件减少30%或更多被认为具有临床意义。在每个实验期结束时，对最后一班的临床医生进行的试验将获得获益-风险评估。该项目的成功完成将为我们的SVS培养箱垫作为一种专用设备的FDA上市许可和商业化提供必要的数据和文件，以改善患有AOP的早产儿的临床结局。

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.