Methylprednisolone vs. Dexamethasone in COVID-19 Pneumonia (MEDEAS RCT)

Summary

Low-dose glucocorticoid treatment is the only intervention shown to significantly reduce mortality in cases of COVID-19 pneumonia requiring oxygen supplementation or ventilatory support. In particular, a large UK randomized controlled trial (RECOVERY trial) demonstrated the efficacy of dexamethasone at a dosage of 6mg/day for 10 days in reducing mortality compared to usual therapy, with a greater impact on patients requiring mechanical ventilation (36% reduction) or oxygen therapy (18% reduction) than on those who did not need respiratory support (doi: 10.1056/NEJMoa2021436). However, there is still paucity of information guiding glucocorticoid administration in severe pneumonia/ARDS and no evidence of the superiority of a steroid drug -nor of a therapeutic scheme- compared to the others, which led to a great heterogeneity of treatment protocols and misinterpretation of available findings. In a recent longitudinal observational study conducted in Italian respiratory high-dependency units, a protocol with prolonged low-dose methylprednisolone demonstrated a 71% reduction in mortality and the achievement of other secondary endpoints such as an increase in ventilation-free days by study day 28 in a subgroup of patients with severe pneumonia and high levels of systemic inflammation (doi: 10.1093/ofid/ofaa421). The treatment was well tolerated and did not affect viral shedding from the airways. In light of these data, the present study aims to compare the efficacy of a methylprednisolone protocol and that of a dexamethasone protocol based on previous evidence in increasing survival by day 28, as well as in reducing the need and duration for mechanical ventilation, among hospitalized patients requiring noninvasive respiratory support (oxygen supplementation and/or noninvasive ventilation).

Timeline

Start

2021-04-14

Primary completion

2022-05-04

Completion

2022-05-04

Publications

• Background RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17.
• Background Arabi YM, Chrousos GP, Meduri GU. The ten reasons why corticosteroid therapy reduces mortality in severe COVID-19. Intensive Care Med. 2020 Nov;46(11):2067-2070. doi: 10.1007/s00134-020-06223-y. Epub 2020 Oct 7. No abstract available.
• Background WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LCP, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JPT, Horby P, Juni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Moller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Oct 6;324(13):1330-1341. doi: 10.1001/jama.2020.17023.
• Background Meduri GU, Annane D, Confalonieri M, Chrousos GP, Rochwerg B, Busby A, Ruaro B, Meibohm B. Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS. Intensive Care Med. 2020 Dec;46(12):2284-2296. doi: 10.1007/s00134-020-06289-8. Epub 2020 Nov 4.
• Background Salton F, Confalonieri P, Meduri GU, Santus P, Harari S, Scala R, Lanini S, Vertui V, Oggionni T, Caminati A, Patruno V, Tamburrini M, Scartabellati A, Parati M, Villani M, Radovanovic D, Tomassetti S, Ravaglia C, Poletti V, Vianello A, Gaccione AT, Guidelli L, Raccanelli R, Lucernoni P, Lacedonia D, Foschino Barbaro MP, Centanni S, Mondoni M, Davi M, Fantin A, Cao X, Torelli L, Zucchetto A, Montico M, Casarin A, Romagnoli M, Gasparini S, Bonifazi M, D'Agaro P, Marcello A, Licastro D, Ruaro B, Volpe MC, Umberger R, Confalonieri M. Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia. Open Forum Infect Dis. 2020 Sep 12;7(10):ofaa421. doi: 10.1093/ofid/ofaa421. eCollection 2020 Oct.
• Background WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. doi: 10.1016/S1473-3099(20)30483-7. Epub 2020 Jun 12.
• Background Dimairo M, Pallmann P, Wason J, Todd S, Jaki T, Julious SA, Mander AP, Weir CJ, Koenig F, Walton MK, Nicholl JP, Coates E, Biggs K, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG; ACE Consensus Group. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ. 2020 Jun 17;369:m115. doi: 10.1136/bmj.m115.
• Reccardini N, Confalonieri M, Ruaro B, Confalonieri P, Da Re B, Rocca A, Salton F. Early C-reactive protein reduction predicts survival in COVID-19 severe pneumonia treated with glucocorticoids. BMC Pulm Med. 2025 Sep 30;25(1):436. doi: 10.1186/s12890-025-03874-9.
• Salton F, Confalonieri P, Centanni S, Mondoni M, Petrosillo N, Bonfanti P, Lapadula G, Lacedonia D, Voza A, Carpene N, Montico M, Reccardini N, Meduri GU, Ruaro B; MEDEAS Collaborative Group; Confalonieri M; MEDEAS Collaborative Group; 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, Lanini S. Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS). Eur Respir J. 2023 Apr 20;61(4):2201514. doi: 10.1183/13993003.01514-2022. Print 2023 Apr.

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