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Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus-Seropositive Adults With Critical Illness: A Randomized Clinical Trial.
- Source :
-
JAMA: Journal of the American Medical Association . 8/22/2017, Vol. 318 Issue 8, p731-740. 10p. 1 Diagram, 3 Charts, 3 Graphs. - Publication Year :
- 2017
-
Abstract
- <bold>Importance: </bold>The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown.<bold>Objective: </bold>To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill.<bold>Design, Setting, and Participants: </bold>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.<bold>Interventions: </bold>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).<bold>Main Outcomes and Measures: </bold>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.<bold>Results: </bold>Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups 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, CMV reactivation in plasma was significantly lower 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. The ganciclovir group had 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). There were no significant differences between the ganciclovir and placebo groups in 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).<bold>Conclusions and Relevance: </bold>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.<bold>Trial Registration: </bold>clinicaltrials.gov Identifier: NCT01335932. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GANCICLOVIR
*CYTOMEGALOVIRUSES
*INTERLEUKIN-6
*VIRUS reactivation
*MEDICAL care of HIV-positive persons
*CRITICALLY ill
*BLOOD plasma
*INTENSIVE care patients
*PHYSIOLOGY
*THERAPEUTICS
*MEDICAL care
*CYTOMEGALOVIRUS disease prevention
*INJURY complications
*ANTIVIRAL agents
*ARTIFICIAL respiration
*CATASTROPHIC illness
*CLINICAL trials
*COMPARATIVE studies
*CYTOMEGALOVIRUS diseases
*LENGTH of stay in hospitals
*INTERLEUKINS
*LONGITUDINAL method
*RESEARCH methodology
*MEDICAL cooperation
*RESEARCH
*RESPIRATORY insufficiency
*STATISTICAL sampling
*SEPSIS
*WOUNDS & injuries
*EVALUATION research
*RANDOMIZED controlled trials
*TREATMENT effectiveness
*BLIND experiment
*DISEASE complications
*PHARMACODYNAMICS
RESPIRATORY insufficiency treatment
Subjects
Details
- Language :
- English
- ISSN :
- 00987484
- Volume :
- 318
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- JAMA: Journal of the American Medical Association
- Publication Type :
- Academic Journal
- Accession number :
- 124813748
- Full Text :
- https://doi.org/10.1001/jama.2017.10569