2/2: PREcision VENTilation to attenuate Ventilation-Induced Lung Injury (PREVENT VILI)

项目摘要/摘要 急性呼吸窘迫综合征(ARDS)发生在高达四分之一的危重成人接受 机械通风，与高发病率和死亡率有关，并与 呼吸机所致肺损伤(VILI)。目前的通风策略和标准护理尝试减少 Vili的效果，但并不是一律成功的。对改进通风策略的需求已经 在新冠肺炎大流行的背景下变得更加迫切和紧迫。潮汐呼吸机精密滴定 容量维持驾驶压力≤12 cm H2O可改善过度膨胀损伤及应用阳离子 呼气末压力(PEEP)滴定至0±2cmH2O的跨肺压可防止损伤 肺部塌陷。这项U24赠款申请将建立一个数据协调中心(DCC)，支持 精确通风以减少VILI临床协调中心(CCC)在进行多中心， 前瞻性第三阶段随机试验，以检验这种精确通风策略将会改善的假设 中重度ARDS患者的60天死亡率与常规指导治疗的比较。DCC将提供 在以下指导下进行试验所需的基础设施、支持、监督和质量控制 目标：目标1-合作制定协议。协调委员会将协助中央协调委员会界定 制定试验的总体计划，并确保在议定书文件中列入必要的章节。目标2 -设计和执行适当的、预先确定的、创新的统计计划，包括研究分析 数据，安全性评估，受益机制的调查，以及促进稿件准备。 目标3-通过提供视频辅助同意，促进以患者为中心、社区参与的研究 材料、应计比率的实时报告，重点是确保不同的参与人口和 通过提供有关不良事件报告的识别和时间安排的明确说明，确保患者的安全 设立数据和安全监测委员会。目标4-支持先进的生理学核心实验室 将生理学专业知识整合到试验进行和数据管理中，并确保严谨和 呼吸机程序指导呼吸机管理中呼吸波形解释的重复性 介入臂。DCC将审查各站点提交的所有生理波形并提供反馈 关于质量和口译。目标5--提供数据管理和监测试验活动。DCC 将在最先进的电子数据捕获系统上建立eCRF。在注册期间，DCC将确保 高质量的数据收集、测量和改进协议遵从性。促进现场沟通和 为确认身份，发展中心将开发一个试验网站和季刊，并协助中心组织会议。 和电话会议。目标6--确保研究和审判后活动的完整性。这包括会议 为参与网站提供里程碑和试验结束支持，并向资助机构提供最终定稿， 识别并锁定供公共使用的数据集。

PROJECT SUMMARY / ABSTRACT Acute respiratory distress syndrome (ARDS) occurs in up to one-quarter of all critically ill adults receiving mechanical ventilation and is associated with high risk of morbidity and mortality, which is compounded by ventilation-induced lung injury (VILI). Current ventilation strategies and standard care attempt to lessen the effects of VILI, but have not been uniformly successful. The need for improved ventilation strategies have become more compelling and urgent in the context of the COVID-19 pandemic. Precise ventilator titration of tidal volumes to maintain driving pressure ≤ 12 cm H2O may improve overdistension injury and application of positive end expiratory pressure (PEEP) with titration to transpulmonary pressure of 0±2cmH2O may prevent injury from lung collapse. This U24 grant application will establish a Data Coordinating Center (DCC) that supports the PREcision VENTilation to attenuate VILI Clinical Coordinating Center (CCC) in conducting a multicenter, prospective phase III randomized trial to test the hypothesis that this precision ventilation strategy will improve 60-day mortality compared to guided usual care in patients with moderate or severe ARDS. The DCC will provide the infrastructure, support, oversight and quality control necessary to conduct this trial guided by the following aims: Aim 1 - To collaborate in the protocol development. The DCC will assist the CCC in defining the overarching plan of the trial, and ensure the inclusion of essential sections within the protocol document. Aim 2 - To design and execute an appropriate, pre-determined, innovative statistical plan including analysis of study data, assessment of safety, investigation of mechanism of benefit, and facilitation of manuscript preparation. Aim 3 – To facilitate a patient centered study, with community engagement, by providing video-assisted consent materials, real-time reporting of accrual rates, with emphasis on ensuring a diverse participant population and ensuring patient safety by providing clear instructions on identification and timing of adverse event reporting and creation of the Data and Safety Monitoring Board. Aim 4 - To support an advanced physiological core laboratory to integrate physiological expertise into trial conduct and data management and to ensure rigor and reproducibility of respiratory waveform interpretation used for protocol-directed ventilator management in the intervention arm. The DCC will review all physiological waveforms submitted by sites and provide feedback regarding quality and interpretation. Aim 5 - To provide data administration and monitor trial activities. The DCC will build the eCRFs on a state-of-the-art electronic data capture system. During enrollment, the DCC will ensure high-quality data collection and measure and improve protocol compliance. To foster site communication and identity, the DCC will develop a trial website and quarterly newsletter, and assist the CCC in organizing meetings and conference calls. Aim 6 - To ensure completeness of the study and post-trial activities. This includes meeting milestones and end-of-trial support for participating sites and providing the funding agency with a finalized, deidentified, and locked data set for public use.