TY - JOUR

T1 - Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia

T2 - The COVID STEROID randomised, placebo-controlled trial

AU - Munch, Marie Warrer

AU - Meyhoff, Tine Sylvest

AU - Helleberg, Marie

AU - Kjær, Maj Brit Nørregaard

AU - Granholm, Anders

AU - Hjortsø, Carl Johan Steensen

AU - Jensen, Thomas Steen

AU - Møller, Morten Hylander

AU - Hjortrup, Peter Buhl

AU - Wetterslev, Mik

AU - Vesterlund, Gitte Kingo

AU - Russell, Lene

AU - Jørgensen, Vibeke Lind

AU - Kristiansen, Klaus Tjelle

AU - Benfield, Thomas

AU - Ulrik, Charlotte Suppli

AU - Andreasen, Anne Sofie

AU - Bestle, Morten Heiberg

AU - Poulsen, Lone Musaeus

AU - Hildebrandt, Thomas

AU - Knudsen, Lene Surland

AU - Møller, Anders

AU - Sølling, Christoffer Grant

AU - Brøchner, Anne Craveiro

AU - Rasmussen, Bodil Steen

AU - Nielsen, Henrik

AU - Christensen, Steffen

AU - Strøm, Thomas

AU - Cronhjort, Maria

AU - Wahlin, Rebecka Rubenson

AU - Jakob, Stephan M.

AU - Cioccari, Luca

AU - Venkatesh, Balasubramanian

AU - Hammond, Naomi

AU - Jha, Vivekanand

AU - Myatra, Sheila Nainan

AU - Jensen, Marie Qvist

AU - Leistner, Jens Wolfgang

AU - Mikkelsen, Vibe Sommer

AU - Svenningsen, Jens S.

AU - Laursen, Signe Bjørn

AU - Hatley, Emma Victoria

AU - Kristensen, Camilla Meno

AU - Al-Alak, Ali

AU - Clapp, Esben

AU - Jonassen, Trine Bak

AU - Bjerregaard, Caroline Løkke

AU - Østerby, Niels Christian Haubjerg

AU - Jespersen, Mette Mindedahl

AU - Abou-Kassem, Dalia

AU - Lassen, Mathilde Languille

AU - Zaabalawi, Reem

AU - Daoud, Mohammed Mahmoud

AU - Abdi, Suhayb

AU - Meier, Nick

AU - la Cour, Kirstine

AU - Derby, Cecilie Bauer

AU - Damlund, Birka Ravnholt

AU - Laigaard, Jens

AU - Andersen, Lene Lund

AU - Mikkelsen, Johan

AU - Jensen, Jeppe Lundholm Stadarfeld

AU - Rasmussen, Anders Hørby

AU - Arnerlöv, Emil

AU - Lykke, Mathilde

AU - Holst-Hansen, Mikkel Zacharias Bystrup

AU - Tøstesen, Boris Wied

AU - Schwab, Janne

AU - Madsen, Emilie Kabel

AU - Gluud, Christian

AU - Lange, Theis

AU - Perner, Anders

N1 - Publisher Copyright: © 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd

PY - 2021

Y1 - 2021

N2 - Background: In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred outcomes in adults with COVID-19 and severe hypoxia. Methods: In this multicentre, parallel-group, placebo-controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID-19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/d) vs a matching placebo for 7 days or until hospital discharge. The primary outcome was the number of days alive without life support at day 28 after randomisation. Results: The trial was terminated early when 30 out of 1000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID-19. At day 28, the median number of days alive without life support in the hydrocortisone vs placebo group were 7 vs 10 (adjusted mean difference: −1.1 days, 95% CI −9.5 to 7.3, P =.79); mortality was 6/16 vs 2/14; and the number of serious adverse reactions 1/16 vs 0/14. Conclusions: In this trial of adults with COVID-19 and severe hypoxia, we were unable to provide precise estimates of the benefits and harms of hydrocortisone as compared with placebo as only 3% of the planned sample size were enrolled. Trial registration: ClinicalTrials.gov: NCT04348305. European Union Drug Regulation Authorities Clinical Trials (EudraCT) Database: 2020-001395-15.

AB - Background: In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred outcomes in adults with COVID-19 and severe hypoxia. Methods: In this multicentre, parallel-group, placebo-controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID-19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/d) vs a matching placebo for 7 days or until hospital discharge. The primary outcome was the number of days alive without life support at day 28 after randomisation. Results: The trial was terminated early when 30 out of 1000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID-19. At day 28, the median number of days alive without life support in the hydrocortisone vs placebo group were 7 vs 10 (adjusted mean difference: −1.1 days, 95% CI −9.5 to 7.3, P =.79); mortality was 6/16 vs 2/14; and the number of serious adverse reactions 1/16 vs 0/14. Conclusions: In this trial of adults with COVID-19 and severe hypoxia, we were unable to provide precise estimates of the benefits and harms of hydrocortisone as compared with placebo as only 3% of the planned sample size were enrolled. Trial registration: ClinicalTrials.gov: NCT04348305. European Union Drug Regulation Authorities Clinical Trials (EudraCT) Database: 2020-001395-15.

KW - corticosteroids

KW - COVID-19

KW - hydrocortisone

KW - placebo-controlled trial

KW - randomised clinical trial

KW - SARS-CoV-2

U2 - 10.1111/aas.13941

DO - 10.1111/aas.13941

M3 - Journal article

C2 - 34138478

AN - SCOPUS:85115113342

VL - 65

SP - 1421

EP - 1430

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 10

ER -