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

Clinical update on COVID-19 for the emergency and critical care clinician: Medical management

“…The COVID STEROID 2 trial included 982 patients and compared dexamethasone 12 mg versus 6 mg in patients with COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. Authors found no difference in median number of days alive without life support (adjusted mean difference 1.3 days, 95% CI 0 to 2.6 days) or mortality at 28 days (27.1% vs. 32.3%, adjusted relative risk 0.86, 95% CI 0.68 to 1.08) [ 14 ]. However, this study may have been underpowered to detect a difference in delays alive without life support or mortality [ 14 ].…”

“…Authors found no difference in median number of days alive without life support (adjusted mean difference 1.3 days, 95% CI 0 to 2.6 days) or mortality at 28 days (27.1% vs. 32.3%, adjusted relative risk 0.86, 95% CI 0.68 to 1.08) [ 14 ]. However, this study may have been underpowered to detect a difference in delays alive without life support or mortality [ 14 ]. A preplanned secondary analysis of the COVID STEROID 2 trial including patients with severe hypoxia (those requiring >10 L of oxygen or on noninvasive ventilation) found that when compared with 6 mg daily, 12 mg daily for up to 10 days increased days alive without life support by 1.3 days, with no difference in adverse events [ 14 ].…”

Effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia: the COVID STEROID 2 randomized trial

“…The COVID STEROID 2 randomized controlled trial did not identify a significant benefit for higher-dose corticosteroids in COVID-19 patients with severe hypoxemia. Following the results of this trial, a pre-planned Bayesian analysis demonstrated a high probability of benefit with the intervention [ 3 ]. Further studies with sufficient power should be performed to better identify the effects of high dose corticosteroids and delineate which COVID-19 patient populations may benefit from higher-dose corticosteroids.…”

Randomised clinical trials in critical care: past, present and future

“…In Bayesian re-analyses of EOLIA and ANDROMEDA-SHOCK, there were 96% and 98% probabilities of benefit with the interventions, respectively, using minimally informative or neutral priors [ 59 , 60 ]; while thresholds for adopting interventions may vary depending on resources/availability, preferences, and cost, these re-analyses led to more nuanced interpretations, with the use of multiple priors allowing readers to form their own context-dependent conclusions. Several Bayesian analyses have been conducted post hoc [ 59 , 60 , 64 – 66 ], sometimes motivated by apparently clinically important effect sizes that did not reach statistical significance, while others have been pre-specified [ 61 , 62 , 67 ], which is preferable as selection driven by trial results is thus avoided.…”