Low versus High Transitional Oxygen Saturation Targets for Preterm Resuscitation in the Delivery Room: A Randomized Controlled Trial

 描述（由申请人提供）：该NIH K23提案描述了候选人的4年培训和研究计划，候选人是一名医生科学家，其长期目标是成为一名具有新生儿临床试验专业知识的独立研究者，重点关注新生儿复苏，新生儿氧（O2）治疗的优化和氧化应激相关疾病的预防。为了实现这些目标，候选人和他的导师提出了一个综合计划，包括一个新的研究思路和氧化应激病理生理学和临床试验的培训，重点是新生儿复苏。早产儿是导致神经发育不良和死亡的各种疾病的高发人群。氧化应激在许多这些疾病的病理生理学中起着重要作用。即使在产房（DR）复苏期间短暂使用高O2浓度，也会加剧反应性O2物质的产生，这会压倒新生儿的抗氧化能力，并可能损害各种器官。在早产儿中，多项小型临床研究表明，减少DR中的O2负荷可降低氧化应激并改善临床结局。然而，缺乏来自适当把握度的随机对照试验的明确证据。研究表明，在健康的足月新生儿中，出生后至少需要5分钟，血氧饱和度（SpO 2）从约50%上升到90%以上。这些被称为过渡目标SpO 2。在之前的研究中，候选人已经证明了在21% O2的产房中开始早产新生儿复苏并根据过渡目标SpO 2调整O2量的可行性。作为这项工作的自然延伸，现在候选人专注于早产儿的最佳过渡目标SpO 2。他之前工作的初步数据表明，目前推荐的过渡目标SpO 2（Ox 50）可能过高，导致早产儿过量的O2暴露和氧化应激。候选人假设，与目前推荐的高目标O2饱和度策略（Ox 50）相比，低目标O2饱和度策略（Ox 10 -25）将导致早产儿成功复苏，O2暴露量更少，氧化应激减少。为了检验这一假设，将在24-28周胎龄婴儿中进行一项前瞻性、随机、对照试验，比较Ox 10 -25与Ox 50。提出了以下三个具体目标。确定Ox 10 -25新生儿是否会降低DR O2暴露和早期氧化应激（目标1），是否需要较少的DR辅助支持（目标2），从而降低不良临床结局的发生率（目标3）。这将是第一个临床试验评估两个不同的过渡SpO 2目标早产复苏的DR。初步数据从这项研究将被用来设计一个更大的临床试验动力的神经发育的结果，这将形成的基础上，候选人的R 01申请接近年底的K23奖。本研究将提供关键信息，以优化DR中的O2治疗，并有可能改善临床 早产儿的结局。

 DESCRIPTION (provided by applicant): This NIH K23 proposal described a 4 year training and research plan for the candidate, a physician scientist with a long term goal of becoming an independent investigator with expertise in neonatal clinical trials with a focus on neonatal resuscitation, optimization of oxygen (O2) therapy in the newborn and prevention of oxidative stress related morbidities. To accomplish these goals, the candidate and his mentors put forth an integrated plan encompassing a novel research idea and training in oxidative stress pathophysiology and clinical trials with a focus on neonatal resuscitation. Premature infants have high incidence of various morbidities leading to poor neurodevelopment and mortality. Oxidative stress plays an important role in the pathophysiology of many of these morbidities. The use of high O2 concentrations, even for brief periods during delivery room (DR) resuscitation exacerbates the generation of reactive O2 species which can overwhelm newborn antioxidant capacity and may damage various organs. In preterm infants, multiple small clinical studies have shown that a reduction in the O2 load in the DR decreases oxidative stress and improves clinical outcomes. However, definitive evidence from appropriately powered randomized controlled trial is lacking. Studies have demonstrated that in healthy term newborns it takes at least 5 minutes after birth for the oxygen saturation (SpO2) to rise from around 50% to greater than 90%. These are called the transitional goal SpO2. In previous studies, the candidate has demonstrated the feasibility of initiating resuscitation of a preterm neonate in the delivery room with 21% O2 and adjusting the O2 amount based on the transitional goal SpO2. As a natural extension of this work, now the candidate is focusing on what the optimal transitional goal SpO2 should be in preterm infants. Preliminary data from his previous work show that the current recommended transitional goal SpO2 (Ox50) may be too high and results in excess O2 exposure and oxidative stress in preterm neonates. The candidate hypothesizes that a low target O2 saturation strategy (Ox10-25) will result in successful resuscitation of preterm neonates with less O2 exposure and reduction in oxidative stress compared to the currently recommended high target O2 saturation strategy (Ox50). To test this hypothesis, a prospective, randomized, controlled trial of Ox10-25 versus Ox50 in 24-28 weeks gestational age infants will be conducted. The following three specific aims are proposed. To determine if Ox10-25 neonates will have decreased DR O2 exposure and early oxidative stress (Aim 1), will require less DR ventilatory support (Aim 2) and in turn will have reduced incidence of adverse clinical outcomes (Aim 3). This will be the first clinical trial evaluating two different transitioal SpO2 targets for preterm resuscitation in the DR. Preliminary data from this study will be used to design a larger clinical trial powered for neurodevelopmental outcomes which will form the basis of the candidate's R01 application toward the end of the K23 award. This study will provide critical information to optimize O2 therapy in the DR and has potential to improve clinical outcomes in preterm neonates.