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

1/2 PROSpect：俯卧和摆动儿科临床试验 (CCC)

• 批准号: 10480739
• 负责人: Ira M Cheifetz
• 金额: $ 169.25万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480739
• 关键词: Acute Respiratory Distress Syndrome; Adult; Back; Cannulations; Caring; Child; Child Care; Childhood; Clinical; Clinical Trials; Consensus; Critical Care; Critical Illness; Critically ill children; Data; Eligibility Determination; Extracorporeal Membrane Oxygenation; Frequencies; Futility; Gravitation; Growth and Development function; Guidelines; High-Frequency Ventilation; Homeostasis; Hospital Mortality; Hospitals; Hour; Hypercapnia; Hypoxia; Immune response; Inferior; Intention; International; Intervention; Intratracheal Intubation; Length of Stay; Life; Link; Lung; Mechanical ventilation; Mission; Monitor; Multiple Organ Failure; National Heart, Lung, and Blood Institute; Organ failure; Oxygen; Patient-Focused Outcomes; Patients; Pediatric Acute Lung Injury; Pediatric Acute Respiratory Distress Syndrome; Pediatric Intensive Care Units; Perfusion; Probability; Prone Position; Protocols documentation; Publications; Randomized; Randomized Controlled Clinical Trials; Research; Safety; Secondary to; Strategic Planning; Supination; Supine Position; Survivors; Tidal Volume; Update; Ventilator; Volutrauma; age group; atelectrauma; base; clinical practice; experience; functional status; health related quality of life; improved; lung injury; meetings; pediatric patients; pressure; prevent; primary outcome; respiratory; response; risk benefit ratio; secondary outcome; surfactant; symposium; ventilation

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.

项目摘要 虽然急性呼吸窘迫综合征是一种危及生命的常见问题， 每年有成千上万的儿童，几乎没有证据支持他们在危重疾病期间的最佳通气实践。 超过25年来，儿科重症监护临床医生一直在争论仰卧位与俯卧位的风险效益比 体位和常规机械通气（CMV）与高频振荡通气 （HFOV）在这些年轻患者的管理。如果没有儿科的具体数据，如何最好地 将继续对患有严重儿科急性呼吸窘迫综合征（PARDS）的儿童进行护理， 阻碍儿科重症监护领域的发展。 我们提出前景（PRone和振荡儿科临床试验），一个2 × 2的析因，反应- 仰卧位/俯卧位和CMV/HFOV的适应性随机对照临床试验。45例儿科 重症监护室（PICU），30个美国和15个国际（2/3：1/3分开），至少5年经验 在严重PARDS儿科患者的护理中使用俯卧位和HFOV，可以提供背部- 体外膜肺氧合（ECMO）支持将参与。合格的连续受试者， 重度PARDS将在符合合格性标准后48小时内和 四组之一的气管内插管：仰卧/CMV、俯卧/CMV、仰卧/HFOV、俯卧/HFOV。科目 因持续缺氧或高碳酸血症而未能接受指定体位和/或通气治疗的患者， 在考虑ECMO插管时接受互惠治疗。我们的主要成果是 无呼吸机日（VFD），其中非幸存者接受零VFD。我们假设患有严重 采用俯卧位或HFOV治疗的PARDS将显示≥2个以上的VFD。我们的次要 结果是无非肺器官衰竭天数。我们还将探讨倾向于 在VFD上使用HFOV定位，并研究这些干预措施对90天住院的影响 死亡率以及幸存者的机械通气持续时间、PICU和住院时间，以及 PICU后功能状态和健康相关生活质量（HRQL）的轨迹。多达1000例受试者， 重度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例受试者提供完整的VFD数据后开始。任何在预先计划的 将取消自适应随机化更新分析，以增加对上级组的分配。数据 将根据意向治疗和收到的符合方案进行分析。 这项临床试验将为该领域考虑重大变革提供必要的明确证据 在临床实践中护理重症PARDS患儿。