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)：这份NIH K23提案描述了候选人的4年培训和研究计划，他是一名内科科学家，长期目标是成为一名独立研究员，在新生儿临床试验方面具有专业知识，重点是新生儿复苏、新生儿氧气(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，其中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方面的培训，重点是新生儿复苏。早产儿各种疾病发生率高，导致神经发育不良，死亡率高。氧化应激在许多此类疾病的病理生理学中起着重要作用。使用高浓度的O2，即使是在产房(DR)复苏期间很短的一段时间，也会加剧活性O2物种的产生，这可能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，DR中O2负荷的减少减少了氧化应激，并改善了临床结果。然而，缺乏来自适当有效的随机对照试验的确凿证据。研究表明，健康足月新生儿的血氧饱和度(SpO2)在出生后至少需要5分钟才能从50%左右上升到90%以上。这些被称为过渡目标SpO2。在之前的研究中，候选人已经证明了在产房用21%的氧气启动早产儿复苏并根据过渡目标SpO2调整氧气量的可行性。作为这项工作的自然延伸，现在候选人关注的是早产儿的最佳过渡目标SpO2应该是什么。他之前工作的初步数据显示，目前推荐的过渡目标SpO2(Ox50)可能过高，导致早产儿暴露过量氧气和氧化应激。候选人假设低目标氧饱和度策略(Ox10-25)将导致早产儿成功复苏，与目前推荐的高目标氧饱和度策略(Ox50)相比，早产儿的氧气暴露较少，氧化应激减轻。为了验证这一假设，将在24-28周的胎龄婴儿中进行一项前瞻性、随机、对照试验，分别是Ox10-25和Ox50。提出了以下三个具体目标。要确定Ox10-25新生儿是否会减少DR O2暴露和早期氧化应激(目标1)，将需要更少的DR呼吸机支持(目标2)，并反过来将降低不良临床结果的发生率(目标3)。这将是第一次临床试验，评估两种不同的过渡性SpO2目标用于早产复苏，这项研究的初步数据将用于设计一项更大规模的临床试验，为神经发育结果提供动力，这将构成候选人在K23奖项即将结束时申请R01的基础。这项研究将为优化DR的氧气治疗提供关键信息，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.