Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)

饱和目标和复苏试验的优化 (OptiSTART)

• 批准号: 10669164
• 负责人: Vishal S Kapadia
• 金额: $ 50.74万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-21 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669164
• 关键词: 2 year old; Address; Admission activity; Age; Biological Markers; Birth; Blood specimen; Bradycardia; Bronchopulmonary Dysplasia; Cessation of life; Clinical Trials; Data; Delivery Rooms; Enrollment; Equilibrium; Expert Opinion; Funding; Gestational Age; Goals; Guidelines; Hour; Hyperoxia; Hypoxia; Incidence; Infant; Intervention; Isoprostanes; Knowledge; Link; Lung; Measures; Morbidity - disease rate; Multicenter Neonatal Research Network; National Institute of Child Health and Human Development; Neurodevelopmental Impairment; Outcome; Oxidative Stress; Oxygen; Patients; Pilot Projects; Premature Infant; Pulmonary Hypertension; Pulmonary Vascular Resistance; Randomized; Randomized, Controlled Trials; Recommendation; Research; Respiratory Failure; Resuscitation; Site; Specific qualifier value; Survival Rate; Testing; Time; Titrations; Umbilical Cord Blood; adverse outcome; design; improved; improved outcome; intraventricular hemorrhage; mortality; neonatal care; neonatal outcome; neonatal resuscitation; positive airway pressure; primary outcome; programs; respiratory; secondary outcome

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.

项目摘要 这项研究旨在回答早产复苏的知识的基本差距之一 婴儿出生时：最佳靶氧饱和度（SPO2）是什么，它在没有长期的情况下增加了存活率 术语病毒？氧气（O2）通常用于稳定在分娩室中的早产儿 （DR），但其用途与死亡率和包括支气管肺发育不良（BPD）在内的几种病态有关。 为了平衡提供足够的O2以纠正缺氧并避免过量O2的需求，新生儿复苏 程序（NRP）建议以低（≤30％）启发的O2浓度（FIO2）开始早产复苏 并随后滴定达到指定的目标SPO2范围。这些SPO2目标基于 在健康的儿童中观察到了大约50％的SPO2（SAT50）。但是，最佳spo2 在早产儿中，靶标仍然不确定。最近的数据表明，无法实现80％的SPO2 到五分钟时，脑室内出血（IVH）和死亡率是有关的。这些研究引起了人们的关注 当前的SPO2靶标（SAT50）可能太低，导致高肺血管的持久性 阻力，呼吸衰竭和死亡率。来自我的NICHD K23的初步数据随机 75位早产儿的对照试验（RCT）<31周胎龄（GA），表明婴儿随机分配给 第75个百分位数SPO2进球（SAT75）在DR中五分钟的SPO2 <80％的事件较低，而不是 婴儿随机分为50％SPO2目标（SAT50）。此外，SAT75婴儿在 出生后一个小时，入院时需要少呼吸支持，肺动脉高压较少，并且 没有BPD的较高生存率。我们假设早产儿的分娩室复苏<31周 与SAT50目标相比，具有SAT75目标的GA将在36周内增加生存率，而无需BPD。 月经后年龄（PMA）。我们计划进行SAT75的多中心RCT，而SAT50为生存供电 没有BPD。我们将将772名婴儿（230/7-306/7周）随机分为SAT75（干预）或SAT50（对照）。 除SPO2目标外，所有复苏都将遵循NRP指南，包括初始FIO2为0.3。目标 1，我们将确定针对SAT75与SAT50相比，无BPD是否会增加生存率。此外， 我们将比较其他主要病因（例如IVH）的速度。在AIM 2中，我们将确定是否针对 与SAT50相比，SAT75在2岁时没有神经发育障碍的情况下增加了生存率。目标 3，我们将确定针对SAT75与SAT50相比是否降低氧化应激。我们将进行 从单个部位招收的220名婴儿的子研究员均在脐带血和8-ohdg的措施和8-ohdg中 出生后1和24小时收集的血液样本。从这项审判中获得的新理解有 改变新生儿复苏实践并改善全球新生儿结局的潜力。这将是 第一次为生存提供动力的临床试验，没有BPD来评估竞争的DR SPO2目标，并解决了 NRP和NICHD认可的批判知识差距。