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 - Funding Information:
This study is funded by the Novo Nordisk Foundation, Grant/Award Number: 0062998 and supported by Rigshospitalet's Research Council, Grant/Award Number: E‐22703‐06 and Pfizer, Grant/Award Number: 60473019. The funding sources were not involved in designing, conducting, analysing or reporting of the COVID STEROID trial.
Funding Information:
The Department of Intensive Care, Rigshospitalet, has received funds for other research projects from the Novo Nordisk Foundation, Ferring and Fresenius Kabi. TB reports grants from Novo Nordisk Foundation, grants from Lundbeck Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, grants from Kai Hansen Foundation, outside the submitted work. CSU has received personal fees from AstraZeneca, GSK, Chiesi, TEVA, ALK‐Abello, Orion Pharma, Boehringer‐Ingelheim, Sanofi‐Genzyme, Novartis and Actelion outside the submitted work. The Department of Intensive Care Medicine, Bern University Hospital (Inselspital), has or has had research & development/consulting contracts with Edwards Lifesciences Services GmbH, Phagenesis Limited and Nestlé. The money was paid into a departmental fund, and none of the authors received any financial gain. The Department of Intensive Care Medicine, Bern University Hospital (Inselspital), has received unrestricted educational grants from the following organisations for organising bi‐annual postgraduate courses in the fields of critical care ultrasound, management of extracorporeal membrane oxygenation (ECMO) and mechanical ventilation: Pierre Fabre Pharma AG (formerly known as RobaPharm), Pfizer AG, Bard Medica SA, Abbott AG, Anandic Medical Systems, PanGas AG Healthcare, Orion Pharma, Bracco, Edwards Lifesciences AG, Hamilton Medical AG, Fresenius Kabi (Schweiz) AG, Getinge Group Maquet AG, Dräger Schweiz AG, and Teleflex Medical GmbH. The remaining authors have no conflicts of interest to declare.
Publisher Copyright:
© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
PY - 2021/11
Y1 - 2021/11
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
UR - http://www.scopus.com/inward/record.url?scp=85115113342&partnerID=8YFLogxK
U2 - 10.1111/aas.13941
DO - 10.1111/aas.13941
M3 - Journal article
C2 - 34138478
AN - SCOPUS:85115113342
SN - 0001-5172
VL - 65
SP - 1421
EP - 1430
JO - Acta Anaesthesiologica Scandinavica
JF - Acta Anaesthesiologica Scandinavica
IS - 10
ER -