Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)

项目总结 这项研究旨在回答早产复苏方面的一个基本知识空白。 婴儿出生时：最理想的目标血氧饱和度(SpO2)范围是多少，才能在没有长时间... 学期病态？氧气(O2)通常用于产房早产儿的稳定。 (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。 为了平衡提供足够氧气以纠正缺氧和避免过量氧气的需要，新生儿复苏 该计划建议在低(≤30%)激发氧浓度(FiO2)的情况下开始早产复苏 并随后进行滴定，以达到指定的目标SpO2范围。这些SpO2目标是基于 在健康足月婴儿中观察到大约50%的SpO2(Sat50)。然而，最优的SpO2 早产儿的靶点仍未确定。最近的数据表明，无法达到80%的SpO2 超过五分钟与脑室出血(IVH)和死亡率有关。这些研究引起了人们的关注 目前的SpO2指标(Sat_(50))可能太低，导致高肺血管持续存在 耐药性、呼吸衰竭和死亡率。我的NICHD K23资助试验的初步数据随机 对75名早产儿和31周胎龄(GA)的对照试验(RCT)显示，婴儿随机分为 在DR中，75%的SpO2目标(Sat75)在5分钟内SpO2和80%的发生率低于 婴儿随机达到50%的SpO2目标(Sat50)。此外，SAT75婴儿的氧化压力在 出生后一小时，入院时需要的呼吸支持较少，肺动脉高压较少， 没有BPD的情况下存活率更高。我们假设早产儿31周的产房复苏 在没有BPD的情况下，使用Sat75的GA目标比使用Sat50的目标将增加36周的存活率 经后年龄(PMA)。我们计划进行一项多中心随机对照试验(Sat75 vs.Sat50)以求生存 没有BPD。我们将772名胎龄为230/7-306/7周的婴儿随机分为两组，一组为SAT75(干预组)，一组为SAT50(对照组)。 除SpO2目标外，所有复苏都将遵循NRP指南，包括初始FiO2为0.3。在AIM 1，我们将确定靶向Sat75与Sat50相比是否提高了没有BPD的存活率。此外, 我们将比较其他主要疾病的发病率，如IVH。在目标2中，我们将确定目标是否 与SAT50相比，SAT75增加了2岁时的存活率，而没有神经发育障碍。在AIM 3，我们将确定靶向Sat75与Sat50相比是否可以降低氧化应激。我们将进行一项 从同一地点登记的220名婴儿的子研究，测定脐血和脐血中8-iso-PGF_2α和8-OHdG。 分别于出生后1小时和24小时采集血样。从这次审判中获得的新的认识具有 修改新生儿复苏实践和改善全球新生儿结局的潜力。这将是 首个支持在没有BPD的情况下存活的临床试验，以评估相互竞争的DR SpO2目标并解决 NRP和NICHD认识到的关键知识差距。

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.