Laurent Papazian1, Samir Jaber2, Sami Hraiech3, Karine Baumstarck4, Sophie Cayot-Constantin5, Nadia Aissaoui6, Boris Jung7, Marc Leone8, Bertrand Souweine9, Carole Schwebel10, Jérémy Bourenne11, Jérôme Allardet-Servent12, Toufik Kamel13, Qin Lu14, Christine Zandotti15, Anderson Loundou4, Christine Penot-Ragon16, Jean Chastre17, Jean-Marie Forel3, Charles-Edouard Luyt17. 1. Médecine Intensive Réanimation, Aix-Marseille Université, Hôpital Nord, Chemin des Bourrely, 13015, Marseille, France. laurent.papazian@ap-hm.fr. 2. Réanimation Chirurgicale, Centre Hospitalier Universitaire de Montpellier, Hôpital St-Eloi, Montpellier, France. 3. Médecine Intensive Réanimation, Aix-Marseille Université, Hôpital Nord, Chemin des Bourrely, 13015, Marseille, France. 4. Laboratoire de Santé Publique, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Marseille, France. 5. Département de Médecine Periopératoire, CHU Clermont-Ferrand, Clermont-Ferrand, France. 6. Médecine Intensive Réanimation, Hôpital Européen Georges-Pompidou, APHP, Paris, France. 7. Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Montpellier, Hôpital Lapeyronie, Montpellier, France. 8. Service d'Anesthésie-Réanimation, Aix-Marseille Université, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Marseille, France. 9. Réanimation Médicale, CHU Gabriel-Montpied, Clermont-Ferrand, France. 10. Médecine Intensive Réanimation, CHU Grenoble Alpes, La Tronche, France. 11. Réanimation des Urgences et Médicale, Aix-Marseille Université, Hôpital Timone, APHM, Marseille, France. 12. Réanimation, Hôpital Européen, Marseille, France. 13. Médecine Intensive Réanimation, Centre Hospitalier Régional, Orléans, France. 14. Réanimation Chirurgicale Polyvalente, Département d'Anesthésie-Réanimation, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, APHP, Paris, France. 15. Laboratoire de Virologie, IHU Méditerranée Infection, CHU Timone UMR190-Emergence des Pathologies Virales, Marseille, France. 16. Pharmacie, Hôpitaux Sud, APHM, Marseille, France. 17. Sorbonne Université, INSERM, Médecine Intensive Réanimation, Institut de Cardiologie, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France.
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.
RCT Entities:
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.
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