PT - JOURNAL ARTICLE AU - Salton, Francesco AU - Confalonieri, Paola AU - Centanni, Stefano AU - Mondoni, Michele AU - Petrosillo, Nicola AU - Bonfanti, Paolo AU - Lapadula, Giuseppe AU - Lacedonia, Donato AU - Voza, Antonio AU - Carpenè, Nicoletta AU - Montico, Marcella AU - Reccardini, Nicolò AU - Meduri, Gianfranco Umberto AU - Ruaro, Barbara AU - MEDEAS Collaborative Group AU - Confalonieri, Marco AU - the MEDEAS Collaborative Group AU - Citton, Gloria Maria AU - Lapadula, Giulia AU - Bozzi, Chiara AU - Tavano, Stefano AU - Pozzan, Riccardo AU - Andrisano, Alessia Giovanna AU - Jaber, Mohamad AU - Mari, Marco AU - Trotta, Liliana AU - Mondini, Lucrezia AU - Barbieri, Mariangela AU - Ruggero, Luca AU - Antonaglia, Caterina AU - Soave, Sara AU - Torregiani, Chiara AU - Bogatec, Tjaša AU - Baccelli, Andrea AU - Nalesso, Giulia AU - Re, Beatrice AU - Pavesi, Stefano AU - Barbaro, Maria Pia Foschino AU - Giuliani, Antonella AU - Ravaglia, Claudia AU - Poletti, Venerino AU - Scala, Raffaele AU - Guidelli, Luca AU - Golfi, Nicoletta AU - Vianello, Andrea AU - Achille, Alessia AU - Lucernoni, Paolo AU - Gaccione, Anna Talia AU - Romagnoli, Micaela AU - Fraccaro, Alessia AU - Malacchini, Nicola AU - Malerba, Mario AU - Ragnoli, Beatrice AU - Zamparelli, Alessandro Sanduzzi AU - Bocchino, Marialuisa AU - Blasi, Francesco AU - Spotti, Maura AU - Miele, Carmen AU - Piedepalumbo, Federica AU - Barone, Ivan AU - Baglioni, Stefano AU - Dodaj, Meridiana AU - Franco, Cosimo AU - Andrani, Francesco AU - Mangia, Angelo AU - Mancini, Annalisa AU - Carrozzi, Laura AU - Rafanelli, Annalisa AU - Casto, Elisabetta AU - Rogliani, Paola AU - Ora, Josuel AU - Carpagnano, Giovanna Elisiana AU - Di Lecce, Valentina AU - Tamburrini, Mario AU - Papi, Alberto AU - Contoli, Marco AU - Luzzati, Roberto AU - Zatta, Marta AU - Di Bella, Stefano AU - Caraffa, Emanuela AU - Francisci, Daniela AU - Tosti, Andrea AU - Pallotto, Carlo AU - De Rosa, Francesco Giuseppe AU - Pecori, Alessio AU - Franceschini, Marta AU - Carlin, Massimiliano AU - Orsini, Valentina AU - Spolti, Anna AU - Inannace, Marta AU - Santantonio, Teresa AU - Meli, Rossella AU - Sauro, Sara AU - Fedeli, Carlo AU - Mangini, Elisabetta AU - Biolo, Gianni AU - Nunnari, Alessio AU - Pietrangelo, Antonello AU - Corradini, Elena AU - Bocchi, Davide AU - Boarini, Chiara AU - Zucchetto, Antonella AU - Lanini, Simone TI - Prolonged higher dose methylprednisolone <em>versus</em> conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS) AID - 10.1183/13993003.01514-2022 DP - 2023 Apr 01 TA - European Respiratory Journal PG - 2201514 VI - 61 IP - 4 4099 - https://publications.ersnet.org//content/61/4/2201514.short 4100 - https://publications.ersnet.org//content/61/4/2201514.full SO - Eur Respir J2023 Apr 01; 61 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