2/2 Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients with Acute Respiratory Failure and Sepsis

项目摘要/摘要 有令人信服的证据表明，巨细胞病毒(CMV)的重新激活是导致 脓毒症相关性呼吸衰竭的发病率和死亡率。3期随机安慰剂对照试验 被称为GRAIL第三阶段的计划是为了确定使用一种名为更昔洛韦的抗病毒药物是否可以 安全有效地预防巨细胞病毒再激活并改善成人脓毒症患者的临床预后- 相关的急性呼吸衰竭。 作为UG3 GRAIL第三阶段临床协调中心(CCC)应用程序的配套，这款U24 应用程序建议建立并运营U24 GRAIL三期数据协调中心(DCC)，以 为拟议的GRAIL第三阶段试验提供统计和数据管理支持。DCC应用程序 有四个目标： ·目标1.总体审判管理和协调。DCC将协助CCC进行全面试验 运营、互动和职能，包括CCC之间的沟通和协调，试验 地点和国家心肺血液研究所(NHLBI)。 ·目标2.协议制定、数据管理和统计支持。DCC将在 GRAIL阶段3的方案开发。它将在试验设计、选择 终点、功率/样本量计算、临时安全监测计划、统计分析计划。这个 数据中心还将使用最先进的电子工具进行灵活可靠的数据收集和管理。 ·目标3.质量保证、数据和安全监测委员会(DSMB)服务和文件 管理层。DCC将协助审查和建立所需的NHLBI流程 质量保证。DCC将与GRAIL第三阶段dsmb合作，协助开发dsmb 宪章，并准备打开和关闭的DSMB报告。DCC将为以下事项制定程序 记录和处理GRAIL第三阶段试验期间的协议偏差/违规。 ·目标4.收尾活动和GRAIL第三阶段后的数据管理。DCC将协助 用于试验收尾活动的CCC。它将协助准备、审查和提交GRAIL第三阶段 用于及时传播审判结果的手稿和演示文稿。DCC还将准备最终的 用于资源共享的带注释的数据集。

PROJECT SUMMARY/ABSTRACT Compelling evidence has emerged to implicate cytomegalovirus (CMV) reactivation as a causal contributor to morbidity and mortality in sepsis-associated respiratory failure. A phase 3 randomized placebo-controlled trial called “GRAIL Phase 3” is planned to determine whether the use of an antiviral drug called ganciclovir can safely and effectively prevent reactivation of CMV and improve clinical outcomes in adults with sepsis- associated acute respiratory failure. As a companion to the UG3 GRAIL Phase 3 Clinical Coordinating Center (CCC) application, this U24 application proposes to establish and operate a U24 GRAIL Phase 3 Data Coordinating Center (DCC) to provide statistical and data management support for the proposed GRAIL Phase 3 trial. The DCC application has four aims: • Aim 1. Overall trial administration and coordination. The DCC will assist the CCC with overall trial operations, interactions and functions, including communication and coordination among the CCC, trial sites, and the National Heart, Lung, and Blood Institute (NHLBI). • Aim 2. Protocol development, data management, and statistical Support. The DCC will collaborate in protocol development for GRAIL Phase 3. It will provide statistical leadership in trial design, choice of endpoint, power/sample size calculation, interim safety monitoring plan, and statistical analysis plan. The DCC will also use state-of-the-art electronic tools for flexible and reliable data collection and management. • Aim 3. Quality assurance, Data and Safety Monitoring Board (DSMB) service, and document management. The DCC will assist with reviewing and establishing the required NHLBI processes for quality assurance. Working with the GRAIL Phase 3 DSMB, the DCC will assist with developing the DSMB Charter, and preparing open and closed DSMB reports. The DCC will establish a procedure for documenting and handling protocol deviations/violations during the GRAIL Phase 3 trial. • Aim 4. Close-out activities and post GRAIL Phase 3 data management. The DCC will assist with the CCC for trial close-out activities. It will assist with preparing, reviewing, and submitting GRAIL Phase 3 manuscripts and presentations for timely dissemination of trial results. The DCC will also prepare final annotated datasets for resource sharing.