Salton F, Confalonieri P, Centanni S, Mondoni M, Petrosillo N, Bonfanti P, Lapadula G, Lacedonia D, Voza A, Carpenè N, Montico M, Reccardini N, Meduri GU, Ruaro B, Confalonieri M, Citton GM, Lapadula G, Bozzi C, Tavano S, Pozzan R, Andrisano AG, Jaber M, Mari M, Trotta L, Mondini L, Barbieri M, Ruggero L, Antonaglia C, Soave S, Torregiani C, Bogatec T, Baccelli A, Nalesso G, Re B, Pavesi S, Barbaro MPF, Giuliani A, Ravaglia C, Poletti V, Scala R, Guidelli L, Golfi N, Vianello A, Achille A, Lucernoni P, Gaccione AT, Romagnoli M, Fraccaro A, Malacchini N, Malerba M, Ragnoli B, Zamparelli AS, Bocchino M, Blasi F, Spotti M, Miele C, Piedepalumbo F, Barone I, Baglioni S, Dodaj M, Franco C, Andrani F, Mangia A, Mancini A, Carrozzi L, Rafanelli A, Casto E, Rogliani P, Ora J, Carpagnano GE, Di Lecce V, Tamburrini M, Papi A, Contoli M, Luzzati R, Zatta M, Di Bella S, Caraffa E, Francisci D, Tosti A, Pallotto C, De Rosa FG, Pecori A, Franceschini M, Carlin M, Orsini V, Spolti A, Inannace M, Santantonio T, Meli R, Sauro S, Fedeli C, Mangini E, Biolo G, Nunnari A, Pietrangelo A, Corradini E, Bocchi D, Boarini C, Zucchetto A, and Lanini S
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 ( P aO 2 / F IO 2 ) 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 P aO 2 / F IO 2 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., Competing Interests: Conflict of interest: F. Salton, P. Confalonieri, S. Centanni, M. Mondoni, N. Petrosillo, D. Lacedonia, A. Voza, N. Carpenè, M. Montico, N. Reccardini, G.U. Meduri, B. Ruaro and M. Confalonieri have no conflicts of interest to disclose. P. Bonfanti received personal fees from ViiV Healthcare, Gilead, Janssen, Merck and Pfizer, not related to this work. G. Lapadula received personal fees from ViiV Healthcare and Pfizer, not related to this work., (Copyright ©The authors 2023.)