The SAIL trial [Sustained Aeration of Infant Lungs]

描述(申请人提供)：美国每年有数千名婴儿死亡或发展为支气管肺发育不良(BPD)。BPD是一种代价高昂的慢性儿童疾病，每年总计花费17,481,047美元。患有BPD的幸存者通常会遭受严重的肺部和/或神经发育后遗症。虽然极低出生体重(出生时1000克)婴儿死亡或BPD的风险很高，但最脆弱的是那些出生在23至26周胎龄(GA)的婴儿。在这一人群中，在最近的支持试验中，死亡率或BPD为68%。该病的发病率或严重程度几乎没有改善。迫切需要新的干预措施。我们研究了两种策略来帮助从充满液体的宫内肺到出生后充满空气的肺的过渡，在生命的最初几分钟。研究人员和前期工作：这项前瞻性多国家随机第三阶段试验由 一支经验丰富、具有国际生产力的试验团队。他们都是通风或产房复苏或两者兼而有之的专家。所有绩效指标和合作机构都参与或领导了多中心或多国家的研究，包括品脱、TIPP、CAP、NIPPV、COIN和支持。总体而言，这项试验的领导者建立了产房氧合的标准值；评估了DR中使用持续充气(SI)建立新生儿呼吸的情况；证明了在产房使用非侵入性支持手段是安全的；测试了各种肺部干预措施；并评估了NICU的输血。方法：我们将对早产儿进行随机对照试验，以确定两种策略中哪一种在出生时最佳地提升肺。具体地说，我们将在600名出生时需要呼吸支持的23-26周GA婴儿中确定两种肺开放策略中的哪一种--在DR中标准的PEEP/CPAP为5-7 cm H2O，与在DR中使用SI的早期肺复张相比，哪种策略会导致36周PMA时死亡或BPD(使用标准化氧气还原试验)的联合终点发生率较低？我们还将比较哪些患者在校正年龄18-24个月时，其他重要的二次结局的发生率较低，包括神经发育损害率。这些问题的答案与日内瓦排雷中心的使命高度相关。试验结果将影响ILCOR和NRP指南。环境：宾夕法尼亚大学的联合临床和数据协调站点在进行大型国际试验方面有着良好的记录。我们已经与世界各地的十名非常有影响力和公认的现场调查人员合作。我们相信这项试验在这些网站内是可行的， 所有这些都成功地完成了之前许多有影响力的早产儿临床试验。这些试验经常改变临床实践。

DESCRIPTION (provided by applicant): Thousands of babies per year die or develop Bronchopulmonary Dysplasia (BPD) in the US. BPD is a costly chronic childhood illness, and costs in total $17,481,047 annually. Survivors with BPD often suffer serious pulmonary and/or neurodevelopmental sequelae. While extremely-low birth-weight (<1000 g at birth) infants are at high risk of death or BPD, the most vulnerable are those born between 23 and 26 weeks' gestational age (GA). In this population, the rate of death or BPD was 68% in the recent 'SUPPORT' trial. There has been little improvement in incidence or severity of the disease. Novel interventions are urgently needed. We investigate two strategies to assist the transition from a fluid-filled in-utero lung to an air-filled lung after birth, in the first vital few minutesof life. Investigators and Prior Work: This prospective multi-national randomized Phase III trial, is led by an experienced, international productive team of trialists. They are collectively expert in ventilation or delivery room resuscitation or both. All PIs and co-Is have participated in or led multicenter or multi-national studies including PINT, TIPP, CAP, NIPPV, COIN and SUPPORT. Collectively, the leaders of this trial have established normative values of oxygenation in the delivery room; evaluated the use of a Sustained Inflation (SI) in the DR to establish breathing in the newborn; have demonstrated the use of non-invasive means of support in the delivery room as safe; tested a variety of lung interventions; and evaluated blood transfusion in the NICU. Approach: We will perform a RCT in preterm infants to determine which of two strategies at birth are best to optimally arate the lung. Specifically we will determine in 600 infants of 23-26 weeks GA needing respiratory support at birth which of two lung opening strategies - either a standard PEEP/CPAP of 5-7 cm H2O in the DR, as compared to early lung recruitment using SI in the DR, will result in a lower rate of the combined endpoint of death or BPD (using a standardized oxygen reduction test) at 36 weeks PMA? We will also compare which has the lower rate of other important secondary outcomes including rates of neurodevelopmental impairment at 18- 24 months of corrected age in survivors. The answers to these questions are highly relevant to the mission of the NICHD. Trial results will impact ILCOR and NRP guidelines. Environment: The combined clinical and data coordinating site at University Pennsylvania has a track record in the conduct of large international trials. We have partnered with a total of ten very influentia and recognized site investigators world-wide. We believe this trial is feasible within these sites, all of which have successfully completed many previous influential clinical trials in preterm infants. These trials have often changed clinical practice.