Abstract
BackgroundThe effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation.MethodsThis double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37).ResultsThe primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0–51] and 0 [0–43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups.ConclusionsIn patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.
Highlights
It is generally reported that 60 to 80% of immunocompetent adults are human cytomegalovirus (CMV) seropositive [1, 2]
An interventional trial aiming to determine whether antiviral therapy is safe and effective for preventing CMV reactivation showed that valacyclovir or low-dose valganciclovir were able to decrease CMV reactivation in a general population of critically ill patients [14]
A multicenter double-blind, placebo-controlled, randomized clinical trial conducted in 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure concluded that the prophylactic use of ganciclovir was able to reduce CMV reactivation and increase the number of ventilator-free days, but was unable to lower interleukin-6 levels [15]
Summary
It is generally reported that 60 to 80% of immunocompetent adults are human cytomegalovirus (CMV) seropositive [1, 2]. An interventional trial aiming to determine whether antiviral therapy is safe and effective for preventing CMV reactivation showed that valacyclovir or low-dose valganciclovir were able to decrease CMV reactivation in a general population of critically ill patients [14]. A multicenter double-blind, placebo-controlled, randomized clinical trial conducted in 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure concluded that the prophylactic use of ganciclovir was able to reduce CMV reactivation and increase the number of ventilator-free days, but was unable to lower interleukin-6 levels (main objective) [15]. The present study was designed to assess whether preemptive ganciclovir is able to increase the number of ventilator-free days in patients with CMV reactivation in blood after at least 4 days of invasive mechanical ventilation. The main objec‐ tive of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilatorfree days in patients with CMV blood reactivation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
