Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial-Protocol and statistical analysis plan.

Abstract

INTRODUCTION:

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

METHODS:

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

DISCUSSION:

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

• Authors: Marie Warrer Petersen, Tine Sylvest Meyhoff, Marie Helleberg, Maj-Brit Nørregaard Kjaer, Anders Granholm, Carl Johan Steensen Hjortsø, Thomas Steen Jensen, Morten Hylander Møller, Peter Buhl Hjortrup, Mik Wetterslev, Gitte Kingo Vesterlund, Lene Russell, Vibeke Lind Jørgensen, Klaus Tjelle, Thomas Benfield, Charlotte Suppli Ulrik, Anne Sofie Andreasen, Thomas Mohr, Morten H Bestle, Lone Musaeus Poulsen, Mette Friberg Hitz, Thomas Hildebrandt, Lene Surland Knudsen, Anders Møller, Christoffer Grant Sølling, Anne Craveiro Brøchner, Bodil Steen Rasmussen, Henrik Nielsen, Steffen Christensen, Thomas Strøm, Maria Cronhjort, Rebecka Rubenson Wahlin, Stephan Jakob, Luca Cioccari, Balasubramanian Venkatesh, Naomi Hammond, Vivekanand Jha, Sheila Nainan Myatra, Christian Gluud, Theis Lange, Anders Perner
• Journal: Acta anaesthesiologica Scandinavica (Acta Anaesthesiol Scand) Vol. 64 Issue 9 Pg. 1365-1375 (10 2020) ISSN: 1399-6576 [Electronic] England
• PMID: 32779728 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Chemical References

• Anti-Inflammatory Agents
• Hydrocortisone

Topics

• Adult
• Anti-Inflammatory Agents (therapeutic use)
• COVID-19 (complications)
• Humans
• Hydrocortisone (therapeutic use)
• Hypoxia (complications, drug therapy)
• Research Design
• Treatment Outcome
• COVID-19 Drug Treatment