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. 2021 Feb 11;11(1):33.
doi: 10.1186/s13613-020-00793-2.

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation

Laurent Papazian  1 , Samir Jaber  2 , Sami Hraiech  3 , Karine Baumstarck  4 , Sophie Cayot-Constantin  5 , Nadia Aissaoui  6 , Boris Jung  7 , Marc Leone  8 , Bertrand Souweine  9 , Carole Schwebel  10 , Jérémy Bourenne  11 , Jérôme Allardet-Servent  12 , Toufik Kamel  13 , Qin Lu  14 , Christine Zandotti  15 , Anderson Loundou  4 , Christine Penot-Ragon  16 , Jean Chastre  17 , Jean-Marie Forel  3 , Charles-Edouard Luyt  17 ; Preemptive Herpesviridae Treatment Study Group, REVA Network
Affiliations

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation

Laurent Papazian et al. Ann Intensive Care. .

Abstract

Background: The 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.

Methods: This 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).

Results: The 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.

Conclusions: In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

Keywords: Clinical trial; Immunocompetent; Mechanical ventilation; Mortality; Randomized.

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported. The following conflicts of interest are outside the area of the article. Dr Papazian reports receiving lecture fees from Hamilton. Dr Jaber reports receiving consulting fees from Dräger, Fisher-Paykel, Xenios-Fresenius Medical and Medtronic. Dr Aissaoui reports receiving lecture fees from Astra-Zeneca and Thoratec. Dr Lu reports receiving lectures fees from Aerogen. Dr Chastre reports receiving lecture and consulting fees from Bayer Healthcare, Pfizer, Merck Sharp & Dohme, Aridis, the Medicines Company, Astra Zeneca, Tigenix, Accelerate Diagnotics, Inotrem and Glaxo Smith Kline. Dr Luyt reports receiving lecture fees from ThermoFisher Brahms, Biomérieux, Merck Sharp & Dohme and Aerogen, and consulting fees from Bayer Healthcare, Carmat and Faron. Dr Leone reports receiving fees for lectures from MSD, Pfizer, Octapharma, 3M, Biomérieux and for consulting from Amomed, Aguettant and Gilead. Dr Chastre has received honoraria for lectures, or for participating in advisory boards, from Accelerate Diagnostics, AstraZeneca/Medimmune, Bayer, Cubist/Merck, GSK, Inotrem, Kenta/Aridis, Shionogi and Tigenix.

Figures

Fig. 1
Fig. 1
Flowchart of the study
Fig. 2
Fig. 2
a Survival curves. b Cumulative proportion of patients weaned from invasive mechanical ventilation
Fig. 3
Fig. 3
a Kinetics of the Sequential Organ-Failure Assessment (SOFA) score from Randomization to Day 28 According to Study Group. b Evolution of PaO2/FiO2 ratio from Randomization to Day 28 According to Study Group. PaO2/FiO2 denotes partial oxygen pressure in arterial blood/fraction of inspired oxygen ratio
See this image and copyright information in PMC

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