Effect of ganciclovir on IL-6 levels among cytomegalovirus-seropositive adults with critical illness: A randomized clinical trial

Ajit P. Limaye*, Renee D. Stapleton, Lili Peng, Scott R. Gunn, Louise E. Kimball, Robert Hyzy, Matthew C. Exline, D. Clark Files, Peter E. Morris, Stephen K. Frankel, Mark E. Mikkelsen, Duncan Hite, Kyle B. Enfield, Jay Steingrub, James O’Brien, Polly E. Parsons, Joseph Cuschieri, Richard G. Wunderink, David L. Hotchkin, Ying Q. ChenGordon D. Rubenfeld, Michael Boeckh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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 languageEnglish (US)
Pages (from-to)731-740
Number of pages10
JournalJAMA - Journal of the American Medical Association
Issue number8
StatePublished - Aug 22 2017

ASJC Scopus subject areas

  • Medicine(all)


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