Use of higher-dose corticosteroids is associated with increased mortality in patients with COVID-19 and hypoxia requiring simple or no oxygen, according to clinical trial findings published in The Lancet.
As part of the RECOVERY trial (ClinicalTrials.gov Identifier: NCT04381936), researchers assessed the effects of a corticosteroid dose that was higher than that of usual care in hospitalized patients with COVID-19 and hypoxia, including those requiring no oxygen or simple oxygen. The randomized, controlled, open-label, platform RECOVERY trial assessed the effects of potential treatments in patients hospitalized with COVID-19 on 3 continents.
The study included 1272 adult inpatients with clinically suspected or laboratory-confirmed SARS-CoV-2 infection and clinical evidence of hypoxia (receiving oxygen with or without other forms of respiratory support or with oxygen saturations <92% on room air). Participants were assigned 1:1 to the usual care plus higher-dose CS (n=659; mean [SD] age, 60.2 [18.3] years; 60% male) or usual care with low-dose CS (n=613; mean age, 62.1 [SD 16.6] years; 61% male). Usual care also typically included 6 mg dexamethasone once daily for 10 days or until discharge, if sooner. The primary outcome was 28-day all-cause mortality. Study recruitment occurred from May 25, 2021, to May 13, 2022.
Use of higher-dose corticosteroids was associated with a significant increase in 28-day mortality compared with usual care alone: 19% of patients in the higher-dose corticosteroid group died vs 12% of patients in the usual care group (rate ratio [RR] 1.59; 95% CI, 1.20-2.10; P =.0012). Notably, a similar risk increase was observed in analyses limited to participants with a positive SARS-CoV-2 polymerase chain reaction test, (RR 1.66; 95% CI, 1.25-2.20; P =.0005) and adjusted for baseline age (RR 1.62; 95% CI, 1.21-2.15; P =.0011). An increased risk of the composite secondary outcome of invasive mechanical ventilation or death was likewise associated with allocation to higher-dose corticosteroids vs usual care (20% vs 13%; RR 1.52; 95% CI, 1.18-1.97).
Notably, use of higher-dose corticosteroids vs usual care was also associated with an increase in pneumonia that was not due to COVID-19 (10% vs 6%, respectively; absolute risk increase 3.7%; 95% CI, 0.7-6.6) and with a higher rate of clinically significant hyperglycemia (22% vs 14%, respectively; absolute risk increase 7.4%; 95% CI, 3.2-11.5).
Study limitations include the open-label design and a lack of data on radiologic, virologic, or physiologic outcomes. Also, it is possible the hazards of higher-dose corticosteroid use were overestimated.
“[C]ompared with standard dose corticosteroids, use of higher dose corticosteroids increases mortality for patients with COVID-19 and hypoxia who are not receiving non-invasive or invasive mechanical ventilation,” the study authors concluded. “It remains unclear whether using a higher dose of corticosteroids is beneficial among patients requiring non-invasive or invasive ventilation — the RECOVERY trial continues to study this,” the researchers added.
RECOVERY Collaborative Group. Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2023;401(10387):1499-1507. doi:10.1016/S0140-6736(23)00510-X