Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: The COVID STEROID randomised, placebo-controlled trial

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; corticosteroids; hydrocortisone; placebo-controlled trial; randomised clinical trial.

Conflict of interest statement

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.

© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Screening, allocation and follow‐up [Colour figure can be viewed at wileyonlinelibrary.com]