The SAIL trial [Sustained Aeration of Infant Lungs]

描述（由申请人提供）：在美国，每年有数千名婴儿死亡或发生支气管肺发育不良（BPD）。BPD是一种昂贵的慢性儿童疾病，每年的总费用为17，481，047美元。BPD的幸存者经常遭受严重的肺部和/或神经发育后遗症。虽然极低出生体重（出生时<1000 g）的婴儿死亡或BPD的风险很高，但最脆弱的是那些出生在23至26周胎龄（GA）之间的婴儿。在这一人群中，在最近的“支持”试验中，死亡率或BPD率为68%。这种疾病的发病率和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，以帮助从充满液体的子宫内肺过渡到出生后充满空气的肺，在生命的最初几分钟。研究者和既往工作：这项前瞻性多国随机III期试验由 一个经验丰富的、国际化的、富有成效的试验者团队。他们都是通风或产房复苏或两者兼而有之的专家。所有PI和co-I均参与或领导了多中心或多国研究，包括PINT、TIPP、CAP、NIPPV、COIN和SUPPORT。总的来说，本试验的领导者已经建立了产房氧合的标准值;评价了在DR中使用持续充气（SI）建立新生儿呼吸;证明了在产房使用无创支持手段是安全的;测试了各种肺部干预;并评价了NICU中的输血。方法：我们将在早产儿中进行随机对照试验，以确定出生时两种策略中哪一种最能优化肺。具体而言，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-与在DR中使用SI的早期肺复张相比，在DR中使用5-7 cm H2O的标准PEEP/CPAP，将导致在36周PMA时死亡或BPD（使用标准化减氧试验）的联合终点发生率较低？我们还将比较哪种治疗方案的其他重要次要结局发生率较低，包括幸存者矫正年龄18- 24个月时的神经发育障碍发生率。这些问题的答案与国家排雷中心的使命高度相关。试验结果将影响ILCOR和NRP指南。工作环境：宾夕法尼亚大学的临床和数据协调中心在进行大型国际试验方面有着良好的记录。我们已经与全球十位非常有影响力和公认的研究中心研究人员合作。我们相信在这些地点进行试验是可行的， 所有这些都成功地完成了许多先前在早产儿中的有影响力的临床试验。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.