Introduction: Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking. Methods: We conducted a multi-center, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. Primary outcome: reduction in 28-day mortality. Secondary outcomes: mechanical ventilation-free days at 28 days, need for ICU referral, length of hospitalisation, need for tracheostomy, changes in PaO2:FiO2 ratio, C-reactive protein levels and WHO 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 the median mechanical ventilation-free days (23[14] versus 24[16]; 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 hospitalisation (15[11] versus 14[11] days; p=0.005) and experienced an improvement in C-reactive protein levels, but not in PaO2:FiO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified timepoints. Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared to conventional dexamethasone in COVID-19 pneumonia.

Salton, F., Confalonieri, P., Centanni, S., Mondoni, M., Petrosillo, N., Bonfanti, P., et al. (2022). Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS). EUROPEAN RESPIRATORY JOURNAL [10.1183/13993003.01514-2022].

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Bonfanti, Paolo;Lapadula, Giuseppe;
2022

Abstract

Introduction: Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking. Methods: We conducted a multi-center, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. Primary outcome: reduction in 28-day mortality. Secondary outcomes: mechanical ventilation-free days at 28 days, need for ICU referral, length of hospitalisation, need for tracheostomy, changes in PaO2:FiO2 ratio, C-reactive protein levels and WHO 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 the median mechanical ventilation-free days (23[14] versus 24[16]; 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 hospitalisation (15[11] versus 14[11] days; p=0.005) and experienced an improvement in C-reactive protein levels, but not in PaO2:FiO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified timepoints. Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared to conventional dexamethasone in COVID-19 pneumonia.
Articolo in rivista - Articolo scientifico
COVID-19
English
Salton, F., Confalonieri, P., Centanni, S., Mondoni, M., Petrosillo, N., Bonfanti, P., et al. (2022). Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS). EUROPEAN RESPIRATORY JOURNAL [10.1183/13993003.01514-2022].
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, G; Ruaro, B; Confalonieri, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/396611
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