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

项目总结/摘要 令人信服的证据表明，巨细胞病毒（CMV）的再激活是导致 败血症相关呼吸衰竭的发病率和死亡率。一项III期随机安慰剂对照试验 一项名为“GRAIL第三阶段”的计划旨在确定一种名为更昔洛韦的抗病毒药物的使用是否可以 安全有效地预防CMV再激活并改善脓毒症成人的临床结局- 急性呼吸衰竭。 作为UG 3 GRAIL 3期临床协调中心（CCC）申请的配套产品，该U24 申请建议建立和运营U24 GRAIL第3阶段数据协调中心（DCC）， 为拟定的GRAIL III期试验提供统计和数据管理支持。DCC应用 有四个目标： ·目标1。总体试验管理和协调。DCC将协助CCC进行总体试验 运作、互动和职能，包括CCC之间的沟通和协调， 国家心脏、肺和血液研究所（NHLBI）。 ·目标2。方案开发、数据管理和统计支持。DCC将在以下方面开展合作： GRAIL第3阶段的方案开发。它将在试验设计、选择 终点、把握度/样本量计算、中期安全性监测计划和统计分析计划。的 发展协调委员会还将使用最先进的电子工具进行灵活和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DCC将协助审查和建立所需的NHLBI流程， 质量保证。DCC将与GRAIL第3阶段DSMB合作，协助开发DSMB 章程，并准备开放和封闭的DSMB报告。DCC将建立一个程序， 记录和处理GRAIL III期试验期间的方案偏离/违背。 目标4。收尾活动和GRAIL III期后数据管理。发展协调委员会将协助 试验结束活动的CCC。它将协助准备，审查和提交GRAIL第3阶段 及时传播试验结果的文稿和介绍。DCC还将准备最后的 资源共享的注释数据集。

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.