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Randomized Controlled Trial
. 2022 Oct 20;60(4):2200025.
doi: 10.1183/13993003.00025-2022. Print 2022 Oct.

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial

Carlo Salvarani  1   2   3 , Marco Massari  4   3 , Massimo Costantini  5 , Domenico Franco Merlo  6 , Gabriella Lucia Mariani  6 , Pierluigi Viale  7 , Stefano Nava  8 , Giovanni Guaraldi  9 , Giovanni Dolci  9 , Luca Boni  10 , Luisa Savoldi  6 , Paolo Bruzzi  10 , Caterina Turrà  11 , Mariagrazia Catanoso  12 , Anna Maria Marata  13 , Chiara Barbieri  14 , Annamaria Valcavi  11 , Francesca Franzoni  6 , Silvio Cavuto  6 , Giorgio Mazzi  15 , Romina Corsini  4 , Fabio Trapani  7 , Alessandro Bartoloni  16   17 , Emanuela Barisione  18 , Chiara Barbieri  19 , Giulia Jole Burastero  9 , Angelo Pan  20 , Walter Inojosa  21 , Raffaele Scala  22 , Cecilia Burattini  23 , Fabrizio Luppi  24 , Mauro Codeluppi  25 , Kamal Eldin Tarek  26 , Giovanni Cenderello  27 , Mario Salio  28 , Giuseppe Foti  29 , Roberto Dongilli  30 , Gianluigi Bajocchi  12 , Emanuele Alberto Negri  31 , Giacomo Ciusa  4   9 , Giacomo Fornaro  7 , Ilaria Bassi  8 , Lorenzo Zammarchi  16   17 , Teresita Aloè  18 , Nicola Facciolongo  19
Affiliations
Randomized Controlled Trial

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial

Carlo Salvarani et al. Eur Respir J. .

Abstract

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia.

Methods: In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival.

Results: Overall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0-17.0 days and 16 days, 95% CI 13.8-18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71-1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0% versus 16.1%; HR 1.26, 95% CI 0.74-2.16; p=0.176) or overall mortality (10.0% versus 12.2%; HR 0.83, 95% CI 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups.

Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia.

Trial registration: ClinicalTrials.gov NCT04673162.

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Conflict of interest statement

Conflict of interest: The authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
The Consolidated Standards of Reporting Trials flow diagram of the study. ITT: intention to treat; SAE: serious adverse event.
FIGURE 2
FIGURE 2
Kaplan–Meier estimates of a) hospital discharge without oxygen; b) orotracheal intubation or death; and c) death. S: standard treatment; MTP: methylprednisolone; HR: hazard ratio.
See this image and copyright information in PMC

Comment in

References

    1. Welte T, Ambrose LJ, Sibbring GC, et al. . Current evidence for COVID-19 therapies: a systematic literature review. Eur Respir Rev 2021; 30: 200384. doi:10.1183/16000617.0384-2020 - DOI - PMC - PubMed
    1. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids – new mechanisms for old drugs. N Engl J Med 2005; 353: 1711–1723. doi:10.1056/NEJMra050541 - DOI - PubMed
    1. Gustine JN, Jones D. Immunopathology of hyperinflammation in COVID-19. Am J Pathol 2021; 191: 4–17. doi:10.1016/j.ajpath.2020.08.009 - DOI - PMC - PubMed
    1. Cassone G, Dolci G, Besutti G, et al. . Acute-phase reactants during tocilizumab therapy for severe COVID-19 pneumonia. Clin Exp Rheumatol 2020; 38: 1215–1222. - PubMed
    1. Fauci AS, Dale DC, Balow JE. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 1976; 84: 304–315. doi:10.7326/0003-4819-84-3-304 - DOI - PubMed

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