Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).
Eur Respir J
; 61(4)2023 04.
Article
em En
| MEDLINE
| ID: mdl-36356972
ABSTRACT
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 6â 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 80â mg as a continuous daily infusion for 8â days followed by slow tapering versus dexamethasone 6â mg once daily for up to 10â 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 28â 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 aO2 /F IO2 ) 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)â 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)â days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 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 28â days compared with conventional dexamethasone in COVID-19 pneumonia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
COVID-19
Tipo de estudo:
Clinical_trials
/
Guideline
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article