Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients.
Fiche publication
Date publication
mars 2020
Journal
Trials
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Pr SAULEAU Erik-André, Dr CARAPITO Raphaël, Pr GENY Bernard
Tous les auteurs :
Pottecher J, Noll E, Borel M, Audibert G, Gette S, Meyer C, Gaertner E, Legros V, Carapito R, Uring-Lambert B, Sauleau E, Land WG, Bahram S, Meyer A, Geny B, Diemunsch P
Lien Pubmed
Résumé
Acute respiratory distress syndrome continues to drive significant morbidity and mortality after severe trauma. The incidence of trauma-induced, moderate-to-severe hypoxaemia, according to the Berlin definition, could be as high as 45%. Its pathophysiology includes the release of damage-associated molecular patterns (DAMPs), which propagate tissue injuries by triggering neutrophil extracellular traps (NETs). NETs include a DNA backbone coated with cytoplasmic proteins, which drive pulmonary cytotoxic effects. The structure of NETs and many DAMPs includes double-stranded DNA, which prevents their neutralization by plasma. Dornase alfa is a US Food and Drug Administration-approved recombinant DNase, which cleaves extracellular DNA and may therefore break up the backbone of NETs and DAMPs. Aerosolized dornase alfa was shown to reduce trauma-induced lung injury in experimental models and to improve arterial oxygenation in ventilated patients.
Mots clés
Acute respiratory distress syndrome, Adult, Deoxyribonuclease I, Hypoxaemia, Multiple trauma, Neutrophil extracellular traps, Randomized controlled trial
Référence
Trials. 2020 Mar 18;21(1):274