IMPORTANCE: The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. OBJECTIVE: To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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). MAIN OUTCOMES AND MEASURES: The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days. RESULTS: Among 160 randomized patients (mean age, 57 years; women, 43%), 156 received 1 or more dose(s) of treatment, and 132 (85%) completed the study. The mean between-group change in IL-6 level was not significantly different. Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group. The ganciclovir group had more VFDs in both the intention-to-treat population and in the prespecified sepsis subgroup. There were no significant between-group differences in other secondary outcomes. (Table Presented) CONCLUSIONS AND RELEVANCE: Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01335932.
|Original language||English (US)|
|Number of pages||10|
|Journal||JAMA - Journal of the American Medical Association|
|State||Published - Aug 22 2017|
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