Low‐dose hydrocortisone in patients with COVID‐19 and severe hypoxia: The COVID STEROID randomised, placebo‐controlled trial
Authors: Munch Marie Warrer , Meyhoff Tine Sylvest , Helleberg Marie , Kjær Maj‐Brit Nørregaard , Granholm Anders , Hjortsø Carl Johan Steensen , Jensen Thomas Steen , Møller Morten Hylander , Hjortrup Peter Buhl , Wetterslev Mik , Vesterlund Gitte Kingo , Russell Lene , Jørgensen Vibeke Lind , Kristiansen Klaus Tjelle , Benfield Thomas , Ulrik Charlotte Suppli , Andreasen Anne Sofie , Bestle Morten Heiberg , Poulsen Lone Musaeus , Hildebrandt Thomas , Knudsen Lene Surland , Møller Anders , Sølling Christoffer Grant , Brøchner Anne Craveiro , Rasmussen Bodil Steen , Nielsen Henrik , Christensen Steffen , Strøm Thomas , Cronhjort Maria , Wahlin Rebecka Rubenson , Jakob Stephan M. , Cioccari Luca , Venkatesh Balasubramanian , Hammond Naomi , Jha Vivekanand , Myatra Sheila Nainan , Jensen Marie Qvist , Leistner Jens Wolfgang , Mikkelsen Vibe Sommer , Svenningsen Jens S. , Laursen Signe Bjørn , Hatley Emma Victoria , Kristensen Camilla Meno , Al‐Alak Ali , Clapp Esben , Jonassen Trine Bak , Bjerregaard Caroline Løkke , Østerby Niels Christian Haubjerg , Jespersen Mette Mindedahl , Abou‐Kassem Dalia , Lassen Mathilde Languille , Zaabalawi Reem , Daoud Mohammed Mahmoud , Abdi Suhayb , Meier Nick , la Cour Kirstine , Derby Cecilie Bauer , Damlund Birka Ravnholt , Laigaard Jens , Andersen Lene Lund , Mikkelsen Johan , Jensen Jeppe Lundholm Stadarfeld , Rasmussen Anders Hørby , Arnerlöv Emil , Lykke Mathilde , Holst‐Hansen Mikkel Zacharias Bystrup , Tøstesen Boris Wied , Schwab Janne , Madsen Emilie Kabel , Gluud Christian , Lange Theis , Perner Anders 
Published: June 2021

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.