Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)

项目摘要 本研究旨在回答早产儿复苏知识的基本空白之一， 出生时的婴儿：增加存活率而不长时间的最佳目标血氧饱和度（SpO 2）范围是多少？ 长期发病率？氧气（O2）通常用于稳定分娩室中的早产儿 (DR)但它的使用与死亡率和包括支气管肺发育不良（BPD）在内的几种疾病有关。 为了平衡给予足够的O2以纠正缺氧和避免过量O2的需要，新生儿复苏 计划（NRP）建议在低（≤ 30%）吸入O2浓度（FiO 2）的情况下启动早产儿复苏 随后进行滴定，以达到指定的目标SpO 2范围。这些SpO 2目标基于 在健康足月婴儿中观察到的近似第50百分位SpO 2（Sat 50）。然而，最佳SpO 2 在早产儿中的目标仍然不明确。最近的数据表明，无法达到80%的SpO 2 与脑室内出血（IVH）和死亡率相关。这些研究引起了人们的关注 当前SpO 2目标（Sat 50）可能过低，导致肺血管持续高血压 抵抗力、呼吸衰竭和死亡率。来自我的NICHD K23资助的试点随机化的初步数据 75例胎龄<31周的早产儿的随机对照试验（RCT）显示， DR中第75百分位SpO 2目标（Sat 75）在5分钟时SpO 2 <80%的发生率较低， 婴儿随机分配至第50百分位SpO 2目标（Sat 50）。此外，Sat 75婴儿的氧化应激水平较低， 出生后1小时，入院时需要较少的呼吸支持，肺动脉高压较少， 没有BPD的生存率更高。我们假设早产儿的产房复苏< 31周 与Sat 50目标相比，具有Sat 75目标的GA将使无BPD的生存期增加36周。 经后年龄（PMA）。我们计划进行一项多中心随机对照试验，比较Sat 75与Sat 50的生存率 没有BPD。我们将772名婴儿随机分为Sat 75（干预组）或Sat 50（对照组），GA为230/7- 306/7周。 除SpO 2目标外，所有复苏均将遵循NRP指南，包括初始FiO 2为0.3。在Aim中 1，我们将确定与Sat 50相比，靶向Sat 75是否会增加无BPD的生存率。此外，本发明还提供了一种方法， 我们将比较其他主要疾病如IVH的发病率。在目标2中，我们将确定 与Sat 50相比，Sat 75增加了2岁时无神经发育障碍的生存率。在Aim中 3，我们将确定与Sat 50相比，靶向Sat 75是否会降低氧化应激。我们将进行 在一个研究中心入组的220名婴儿中进行的子研究，以测量脐带血中的8-iso-PGF 2 α和8-OHdG， 在出生后1小时和24小时采集血样。从这次审判中获得的新认识是， 有可能改变新生儿复苏实践并改善全球新生儿结局。这将是 第一项临床试验在无BPD的生存率方面具有效力，以评价竞争性DR SpO 2目标，并解决了 NRP和NICHD承认存在严重的知识差距。

PROJECT SUMMARY This study is designed to answer one of the fundamental gaps in knowledge in the resuscitation of preterm infants at birth: What is the optimal target oxygen saturation (SpO2) range that increases survival without long- term morbidities? Oxygen (O2) is routinely used for the stabilization of preterm infants in the delivery room (DR), but its use is linked with mortality and several morbidities including bronchopulmonary dysplasia (BPD). To balance the need to give sufficient O2 to correct hypoxia and avoid excess O2, the neonatal resuscitation program (NRP) recommends initiating preterm resuscitation with low (≤ 30%) inspired O2 concentration (FiO2) and subsequent titration to achieve a specified target SpO2 range. These SpO2 targets are based on approximated 50th percentile SpO2 (Sat50) observed in healthy term infants. However, the optimal SpO2 targets remain undefined in the preterm infants. Recent data suggest that the inability to achieve SpO2 of 80% by five minutes is associated with intraventricular hemorrhage (IVH) and mortality. These studies raise concern that current SpO2 targets (Sat50) may be too low resulting in persistence of high pulmonary vascular resistance, respiratory failure and mortality. Preliminary data from my NICHD K23 funded pilot randomized controlled trial (RCT) of 75 preterm infants <31 weeks gestational age (GA) showed that infants randomized to 75th percentile SpO2 goals (Sat75) had a lower incidence of SpO2 <80% at five minutes in the DR compared to infants randomized to 50th percentile SpO2 goals (Sat50). In addition, Sat75 infants had less oxidative stress at one hour after birth, needed less respiratory support on admission, had less pulmonary hypertension and had higher survival without BPD. We hypothesize that delivery room resuscitation of preterm infants < 31 weeks GA with Sat75 targets compared to Sat50 targets will increase survival without BPD by 36 weeks’ postmenstrual age (PMA). We plan to conduct a multicenter RCT of Sat75 versus Sat50 powered for survival without BPD. We will randomize 772 infants, 230/7- 306/7 weeks’ GA, to Sat75 (intervention) or Sat50 (control). Except for the SpO2 targets, all resuscitations will follow NRP guidelines including an initial FiO2 of 0.3. In Aim 1, we will determine whether targeting Sat75 compared to Sat50 increases survival without BPD. In addition, we will compare the rates of other major morbidities such as IVH. In Aim 2, we will determine whether targeting Sat75 compared to Sat50 increases survival without neurodevelopmental impairment at 2 years of age. In Aim 3, we will determine whether targeting Sat75 compared to Sat50 decreases oxidative stress. We will conduct a sub-study of 220 infants enrolled from a single site to measure 8-iso-PGF2α and 8-OHdG in cord blood and blood samples collected at 1 and 24 hours after birth. The new understanding gained from this trial has the potential to modify neonatal resuscitation practice and improve neonatal outcomes worldwide. This will be the first clinical trial powered for survival without BPD to evaluate competing DR SpO2 goals and addresses a critical knowledge gap recognized by NRP and NICHD.