RT Journal Article
SR Electronic
T1 Prolonged higher dose methylprednisolone <em>versus</em> conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2201514
DO 10.1183/13993003.01514-2022
VO 61
IS 4
A1 Salton, Francesco
A1 Confalonieri, Paola
A1 Centanni, Stefano
A1 Mondoni, Michele
A1 Petrosillo, Nicola
A1 Bonfanti, Paolo
A1 Lapadula, Giuseppe
A1 Lacedonia, Donato
A1 Voza, Antonio
A1 Carpenè, Nicoletta
A1 Montico, Marcella
A1 Reccardini, Nicolò
A1 Meduri, Gianfranco Umberto
A1 Ruaro, Barbara
A1 MEDEAS Collaborative Group
A1 Confalonieri, Marco
A1 the MEDEAS Collaborative Group
A1 Citton, Gloria Maria
A1 Lapadula, Giulia
A1 Bozzi, Chiara
A1 Tavano, Stefano
A1 Pozzan, Riccardo
A1 Andrisano, Alessia Giovanna
A1 Jaber, Mohamad
A1 Mari, Marco
A1 Trotta, Liliana
A1 Mondini, Lucrezia
A1 Barbieri, Mariangela
A1 Ruggero, Luca
A1 Antonaglia, Caterina
A1 Soave, Sara
A1 Torregiani, Chiara
A1 Bogatec, Tjaša
A1 Baccelli, Andrea
A1 Nalesso, Giulia
A1 Re, Beatrice
A1 Pavesi, Stefano
A1 Barbaro, Maria Pia Foschino
A1 Giuliani, Antonella
A1 Ravaglia, Claudia
A1 Poletti, Venerino
A1 Scala, Raffaele
A1 Guidelli, Luca
A1 Golfi, Nicoletta
A1 Vianello, Andrea
A1 Achille, Alessia
A1 Lucernoni, Paolo
A1 Gaccione, Anna Talia
A1 Romagnoli, Micaela
A1 Fraccaro, Alessia
A1 Malacchini, Nicola
A1 Malerba, Mario
A1 Ragnoli, Beatrice
A1 Zamparelli, Alessandro Sanduzzi
A1 Bocchino, Marialuisa
A1 Blasi, Francesco
A1 Spotti, Maura
A1 Miele, Carmen
A1 Piedepalumbo, Federica
A1 Barone, Ivan
A1 Baglioni, Stefano
A1 Dodaj, Meridiana
A1 Franco, Cosimo
A1 Andrani, Francesco
A1 Mangia, Angelo
A1 Mancini, Annalisa
A1 Carrozzi, Laura
A1 Rafanelli, Annalisa
A1 Casto, Elisabetta
A1 Rogliani, Paola
A1 Ora, Josuel
A1 Carpagnano, Giovanna Elisiana
A1 Di Lecce, Valentina
A1 Tamburrini, Mario
A1 Papi, Alberto
A1 Contoli, Marco
A1 Luzzati, Roberto
A1 Zatta, Marta
A1 Di Bella, Stefano
A1 Caraffa, Emanuela
A1 Francisci, Daniela
A1 Tosti, Andrea
A1 Pallotto, Carlo
A1 De Rosa, Francesco Giuseppe
A1 Pecori, Alessio
A1 Franceschini, Marta
A1 Carlin, Massimiliano
A1 Orsini, Valentina
A1 Spolti, Anna
A1 Inannace, Marta
A1 Santantonio, Teresa
A1 Meli, Rossella
A1 Sauro, Sara
A1 Fedeli, Carlo
A1 Mangini, Elisabetta
A1 Biolo, Gianni
A1 Nunnari, Alessio
A1 Pietrangelo, Antonello
A1 Corradini, Elena
A1 Bocchi, Davide
A1 Boarini, Chiara
A1 Zucchetto, Antonella
A1 Lanini, Simone
YR 2023
UL https://publications.ersnet.org//content/61/4/2201514.abstract
AB Background Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7–10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking.Methods We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (PaO2/FIO2) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14.Results 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in PaO2/FIO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points.Conclusion Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.Infusive methylprednisolone did not show major advantages over conventional dexamethasone in severe COVID-19 pneumonia, confirming the favourable drug class effect of prolonged, low-dose glucocorticoids postulated by current guidelines https://bit.ly/3zxSwMn