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

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 taperingversusdexamethasone 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)versusdexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%)versus41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14)versus24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%)versus45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%)versus9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11)versus14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not inPaO2/FIO2ratio, 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.