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/day) versus 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 1,000 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 versus placebo group were 7 versus 10 (adjusted mean difference: ‐1.1 days, 95% CI ‐9.5 to 7.3, p = 0.79); mortality was 6/16 versus 2/14; and the number of serious adverse reactions 1/16 versus 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.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial

“…The authors thank everyone involved in the COVID STEROID 2 trial (patients and relatives, research staff, clinical staff, investigators, funding sources, and regulatory authorities), and everyone involved in the first COVID STEROID trial [ 28 ], which served as the foundation for the COVID STEROID 2 trial.…”

Systemic administration of glucocorticoids, cardiovascular complications and mortality in patients hospitalised with COVID-19, SARS, MERS or influenza: A systematic review and meta-analysis of randomised trials

“…We included 11 randomised trials that enrolled 8,109 patients ( Table 1 ). Eight randomised trials 4 , 19 , 20 , 21 , 22 , 23 , 24 , 25 were multi-centre, with RECOVERY [4] contributing 80% of all patients to the meta-analysis. The remaining trials 26 , 27 , 28 were conducted in single sites in Iran, Brazil, and Egypt.…”

“… 28-day mortality. Munch 2021 COVID STEROID (Denmark) [23] 30 16:14 Hydrocortisone (IV) (200 mg/day for 7 days) Placebo Hospitalised IMV for > 48 hours prior to screening, pregnancy. Days alive without use of life support at day 28.…”

“…Five trials 19 , 20 , 21 , 23 , 25 were discontinued or terminated early following the positive report from the RECOVERY trial [4] . The trial led by Tang and colleagues [24] was terminated early due to slow recruitment.…”

“…Five trials 4 , 19 , 21 , 25 , 27 , including RECOVERY, enrolled patients with suspected or laboratory confirmed COVID-19. Six trials 20 , 22 , 23 , 24 , 26 , 28 only included patients with confirmed SARS-CoV-2 by PCR testing. Interventions varied across randomised trials: three trials evaluated hydrocortisone 19 , 21 , 23 , four dexamethasone 4 , 25 , 26 , 28 , and four methylprednisolone 20 , 22 , 24 , 27 .…”