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.
The GRAIL Phase 3 study is a confirmatory randomized placebo-controlled clinical trial to examine whether the use of an antiviral drug called ganciclovir can safely and effectively prevent reactivation of a common virus called cytomegalovirus and improve clinical outcomes in adults with sepsis-associated acute respiratory failure. This U24 application proposes to establish and operate a U24 Data Coordinating Center, to provide statistical and data management support for the proposed GRAIL Phase 3 study.
