A Randomized Double-Blind Placebo-Controlled Trial of Ganciclovir/Valganciclovir for Prevention of Cytomegalovirus Reactivation in Acute Injury of the Lung and Respiratory Failure: The GRAIL Study

PI: Boeckh

The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. This research aimed to determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill.

Design, setting, and method: Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States.

Intervention: Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76).

Outcome: The primary outcome was changed in IL-6 level from day 1 to 14. Secondary outcomes were the incidence of CMV reactivation in plasma, mechanical ventilation days, the incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days.