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| [PMID]: | 28829877 |
| [Au] Autor: | Limaye AP; Stapleton RD; Peng L; Gunn SR; Kimball LE; Hyzy R; Exline MC; Files DC; Morris PE; Frankel SK; Mikkelsen ME; Hite D; Enfield KB; Steingrub J; O'Brien J; Parsons PE; Cuschieri J; Wunderink RG; Hotchkin DL; Chen YQ; Rubenfeld GD; Boeckh M |
| [Ad] Endereço: | Division of Allergy and Infectious Diseases, University of Washington, Seattle. |
| [Ti] Título: | Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus-Seropositive Adults With Critical Illness: A Randomized Clinical Trial. |
| [So] Source: | JAMA;318(8):731-740, 2017 08 22. | | [Is] ISSN: | 1538-3598 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | 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 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). 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. |
| [Mh] Termos MeSH primário: |
Antivirais/uso terapêutico
Infecções por Citomegalovirus/prevenção & controle
Citomegalovirus/isolamento & purificação
Ganciclovir/uso terapêutico
Interleucina-6/sangue
Sepse/tratamento farmacológico
Ferimentos e Lesões/tratamento farmacológico
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| [Mh] Termos MeSH secundário: |
Adulto
Idoso
Antivirais/farmacologia
Estado Terminal/mortalidade
Citomegalovirus/fisiologia
Infecções por Citomegalovirus/sangue
Método Duplo-Cego
Feminino
Seguimentos
Ganciclovir/análogos & derivados
Ganciclovir/farmacologia
Seres Humanos
Análise de Intenção de Tratamento
Tempo de Internação
Masculino
Meia-Idade
Respiração Artificial/estatística & dados numéricos
Insuficiência Respiratória/etiologia
Insuficiência Respiratória/terapia
Sepse/sangue
Sepse/complicações
Resultado do Tratamento
Ativação Viral/efeitos dos fármacos
Ferimentos e Lesões/sangue
Ferimentos e Lesões/complicações
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| [Pt] Tipo de publicação: | CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, N.I.H., EXTRAMURAL |
[Nm] Nome de substância:
| 0 (Antiviral Agents); 0 (IL6 protein, human); 0 (Interleukin-6); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir) |
| [Em] Mês de entrada: | 1708 |
| [Cu] Atualização por classe: | 170920 |
[Lr] Data última revisão:
| 170920 |
| [Sb] Subgrupo de revista: | AIM; IM |
| [Da] Data de entrada para processamento: | 170823 |
| [Cl] Clinical Trial: | ClinicalTrial
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| [St] Status: | MEDLINE |
| [do] DOI: | 10.1001/jama.2017.10569 |
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