1/2 PROSpect: Prone and Oscillation Pediatric Clinical Trial (CCC)

项目摘要 虽然急性呼吸窘迫综合症是一种危及生命的常见问题，但 每年有数以千计的儿童，几乎没有证据支持他们在危重疾病期间的最佳通风做法。 25年来，儿科重症监护临床医生一直在争论仰卧位和俯卧位的风险-收益比。 定位和常规机械通气(CMV)与高频振荡通风 (HFOV)在这些年轻患者的管理中。如果没有儿科专用数据，关于如何最好地 将继续为患有严重急性呼吸窘迫综合征(PARDS)的儿童提供护理 阻碍儿科重症监护领域的进展。 我们提出了PROSPECT(倾斜性和振荡性儿科临床试验)，这是一个两乘二因素析因，反应- 仰卧位/俯卧位和CMV/HFOV的适应性随机对照临床试验。45名儿科医生 重症监护病房(PICU)，30个美国人和15个国际人(2/3：1/3平分)，至少5年经验 采用俯卧位和HFOV治疗重症儿科患者，可提供背部- UP体外膜氧合(ECMO)支持将参与。符合条件的连续科目 严重扑克牌将在符合资格标准的48小时内和在4天内随机进行 气管插管分为四组：仰卧位/CMV、俯卧位/CMV、仰卧位/HFOV、俯卧位/HFOV。科目 因持续性低氧或高碳酸血症而未能通过指定的体位和/或机械通气治疗的患者可能 在考虑进行ECMO插管的同时接受对等治疗。我们的主要结果是 无呼吸机日(VFD)，即无人存活的无呼吸机天数。我们假设患有严重疾病的儿童 无论是俯卧定位还是全视野定位治疗的扑克牌都将显示出更多的≥2 VFD。我们的次要 结果是无肺器官衰竭的天数。我们还将探讨PROSE的交互影响 HFOV对VFD的定位，并调查这些干预措施对住院90天的影响 死亡率，以及幸存者的机械通气时间、PICU和住院时间，以及 PICU后功能状态和健康相关生活质量(HRQL)的变化轨迹。多达1000名受试者 严重PARDS将按年龄组和直接/间接肺损伤随机分组。自适应随机化将 在400名受试者提供有关VFD的完整数据后开始。任何在事先计划好的情况下表现出自卑的团体 将取消自适应随机更新分析，增加对上级组的分配(S)。数据 将根据收到的治疗意向和方案进行分析。 这项临床试验将为该领域考虑重大变化提供必要的确凿证据。 在临床实践中护理危重儿童重症皮肤病。

Project Summary Although acute respiratory distress syndrome is a life-threatening and frequent problem experienced by thousands of children each year, little evidence supports best ventilation practices during their critical illness. For over 25 years, pediatric critical care clinicians have debated the risk-benefit ratio of supine versus prone positioning and conventional mechanical ventilation (CMV) versus high-frequency oscillatory ventilation (HFOV) in the management of these young patients. Without pediatric-specific data, the debate of how best to care for children with severe Pediatric Acute Respiratory Distress Syndrome (PARDS) will continue and prevent progress in the field of pediatric critical care. We propose PROSpect (PRone and OScillation PEdiatric Clinical Trial), a two-by-two factorial, response- adaptive, randomized controlled clinical trial of supine/prone positioning and CMV/HFOV. Forty-five pediatric intensive care units (PICUs), 30 U.S. and 15 international (2/3:1/3 split), with at least 5 years of experience with prone positioning and HFOV in the care of pediatric patients with severe PARDS, that can provide back- up extracorporeal membrane oxygenation (ECMO) support will participate. Eligible consecutive subjects with severe PARDS will be randomized within 48 hours of meeting eligibility criteria and within 4 days of endotracheal intubation to one of four groups: supine/CMV, prone/CMV, supine/HFOV, prone/HFOV. Subjects who fail their assigned positional and/or ventilation therapy for either persistent hypoxia or hypercapnia may receive the reciprocal therapy while being considered for ECMO cannulation. Our primary outcome is ventilator-free days (VFD), where non-survivors receive zero VFDs. We hypothesize that children with severe PARDS treated with either prone positioning or HFOV will demonstrate ≥2 more VFDs. Our secondary outcome is nonpulmonary organ failure-free days. We will also explore the interaction effects of prone positioning with HFOV on VFDs and also investigate the impact of these interventions on 90-day in-hospital mortality and, among survivors, the duration of mechanical ventilation, PICU and hospital length of stay, and the trajectory of post-PICU functional status and health-related quality of life (HRQL). Up to 1000 subjects with severe PARDS will be randomized by age group and direct/indirect lung injury. Adaptive randomization will begin after 400 subjects provide complete data on VFDs. Any group demonstrating inferiority at a pre-planned adaptive randomization update analysis will be eliminated to increase allocation to the superior group(s). Data will be analyzed per intention-to-treat and per-protocol received. This clinical trial will provide the definitive evidence necessary for the field to consider a major change in clinical practice in the care of critically ill children with severe PARDS.