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

产房早产复苏的低与高过渡氧饱和度目标：随机对照试验

• 批准号: 9034190
• 负责人: Vishal S Kapadia
• 金额: $ 13.23万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9034190
• 关键词: 8-hydroxy-2' -deoxyguanosine; Address; Antioxidants; Biological; Birth; Blood specimen; Brain; Bronchopulmonary Dysplasia; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Data; Databases; Delivery Rooms; Development Plans; Educational workshop; Enrollment; Equilibrium; Functional disorder; Generations; Gestational Age; Glutathione; Goals; Guidelines; Heart Rate; Hospitals; Hour; Hydrogen Peroxide; Hyperoxia; Hypoxemia; Incidence; Infant; Intervention; Intubation; Kidney; Lung; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Meta-Analysis; Morbidity - disease rate; National Institute of Child Health and Human Development; Neonatal; Neonatal Intensive Care Units; Neurodevelopmental Impairment; Newborn Infant; Organ; Outcome; Oxidative Stress; Oxygen; Oxygen Therapy Care; Physicians; Physiologic pulse; Plasma; Play; Policies; Premature Birth; Premature Infant; Prevention; Proteins; Publishing; Randomized; Randomized Controlled Trials; Registered nurse; Research; Research Personnel; Research Training; Resuscitation; Retinopathy of Prematurity; Role; Scientist; Specific qualifier value; Supplementation; Term Birth; Testing; Time; Training; Umbilical Cord Blood; United States National Institutes of Health; Work; arm; base; career development; design; improved; intraventricular hemorrhage; mortality; neonatal morbidity; neonatal resuscitation; neonate; neurodevelopment; novel; primary outcome; programs; prospective; public health relevance

 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.

 描述（由应用程序提供）：该NIH K23提案描述了候选人的4年培训和研究计划，该计划是一名物理科学家，其长期目标是成为新生儿临床试验中具有专业知识的独立研究者，侧重于新生儿复苏，优化氧气（O2）疗法（O2）治疗新生儿和氧化应激率相关的氧化与氧化与氧化有关。为了实现这些目标，候选人及其导师制定了一个综合计划，其中包括一种新颖的研究思想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。过早的婴儿的各种病因的发病率很高，导致神经发育和死亡率差。氧化应激在许多此类病因的病理生理学中起重要作用。使用高O2浓度，即使在分娩室（DR）复苏期间短期内，也会加剧反应性O2物种的产生，这些物种会压倒新生儿抗氧化能力并可能损坏各种器官。在早产儿中，多次小型临床研究表明，DR中的O2负荷减少可减少氧化物应激并改善临床结局。但是，缺乏来自适当动力的随机对照试验的明确证据。研究表明，在健康的新生儿中，出生后至少需要5分钟才能使氧饱和度（SPO2）从约50％上升到大于90％。这些称为过渡目标SPO2。在先前的研究中，候选人证明了在输送室中以21％O2进行早产的复苏并根据过渡目标SPO2调整O2的可行性。作为这项工作的自然扩展，现在候选人正在关注最佳的过渡目标SPO2在早产儿中应该是什么。他先前工作的初步数据表明，当前建议的过渡目标SPO2（OX50）可能太高，并且早产新生儿的过量O2暴露和氧化应激。候选人假设与当前推荐的高目标O2饱和策略（OX50）相比，较低的目标O2饱和策略（OX10-25）将成功地恢复早产新生儿，而氧化应激的暴露较小，氧化应激的减少减少。为了检验这一假设，将在24-28周内进行OX10-25对OX50的前瞻性，随机，对照试验。提出了以下三个特定目标。为了确定OX10-25新生儿是否会改善O2的暴露和早期氧化物胁迫（AIM 1），将需要较少的DR通气支持（AIM 2），进而需要降低不良临床结果的发生率（AIM 3）。这将是第一次评估DR中早产的两个不同的过渡性复苏目标的临床试验。这项研究的初步数据将用于设计一个用于神经发育结果的较大临床试验，该试验将构成候选人在K23奖项结束时的R01应用程序的基础。这项研究将提供关键信息，以优化DR中的O2治疗，并具有改善临床的潜力 早产新生儿的结果。