Limaye AP, et al. – This study aimed at determining whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL–6) levels in cytomegalovirus (CMV)–seropositive adults who are critically ill due to sepsis or trauma. Among these patients, ganciclovir seemed not reducing IL–6 levels and thus the current study did not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Researchers suggest additional research to determine the clinical efficacy and safety of CMV suppression in this setting.

Methods

• Researchers performed double–blind, placebo–controlled, randomized clinical trial (conducted March 10, 2011–April 29, 2016) with a follow–up of 180 days (November 10, 2016).
• This study included 160 CMV–seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States
• Randomization of patients (1:1) was performed 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).
• Change in IL–6 level from day 1 to 14 was observed as the primary outcome measure.
• For this study, secondary outcomes assessed 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

• 160 patients (mean age, 57 years; women, 43%) were randomized; 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study.
• Between groups, the mean change in plasma IL–6 levels was -0.79 log₁₀ units (-2.06 to 0.48) in the ganciclovir group and -0.79 log₁₀ units (-2.14 to 0.56) in the placebo group (point estimate of difference, 0 [95% CI, -0.3 to 0.3]; P > .99).
• Among secondary outcomes, significantly lower CMV reactivation in plasma was evident in the ganciclovir group (12% [10 of 84 patients] vs 39% [28 of 72 patients]); absolute risk difference, -27 (95% CI, -40 to -14), P<.001.
• In this study, the ganciclovir group indicated more median VFDs in both the intention–to–treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03).
• Findings revealed no marked difference between the ganciclovir and placebo groups regarding duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54).