Treatment with dexamethasone resulted in lower rates of 28-day mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation but not in those who received no respiratory support, according to findings published in the New England Journal of Medicine.
Researchers conducted a controlled, open-label clinical trial (RECOVERY; ClinicalTrials.gov Identifier: NCT04381936) to evaluate the effects of potential treatments in patients hospitalized with COVID-19 in the United Kingdom. The primary outcome was 28-day mortality, with secondary outcomes being the time until hospital discharge and subsequent receipt of invasive ventilation or death in patients who did not receive mechanical ventilation at the beginning of the study.
A total of 6425 patients were randomly assigned to receive oral or intravenous dexamethasone (n=2104) at 6 mg once daily for up to 10 days or usual care alone (n=4321). Mean patient age was 66.1 years and 36% were women. More than half of the patients had ≥1 major coexisting medical condition, including heart disease, chronic lung disease, and diabetes.
At 28 days, mortality was significantly lower in the patients who received dexamethasone compared with patients who received usual care (22.9% vs 25.7%, respectively; rate ratio, 0.83; 95% CI, 0.75-0.93; P <.001). In patients who received invasive mechanical ventilation, mortality was lower in the dexamethasone group compared with the usual care group (29.3% vs 41.4%, respectively; rate ratio, 0.64; 95% CI, 0.51-0.81), which was also true in patients who received oxygen without invasive mechanical ventilation (23.3% vs 26.2%, respectively; rate ratio, 0.82; 95% CI, 0.72-0.94).
Researchers reported that dexamethasone had no clear effect in patients who did not receive any respiratory support at randomization (17.8% vs 14.0%; rate ratio, 1.19; 95% CI, 0.91-1.55). Furthermore, patients with longer duration of symptoms — who were therefore more likely to have been receiving mechanical ventilation — had an increased mortality benefit with dexamethasone.
Compared with patients in the usual care group, patients who received dexamethasone had shorter duration of hospitalization (median, 13 vs 12 days, respectively) and a greater chance of being discharged alive within 28 days (rate ratio, 1.10; 95% CI, 1.03-1.17). Patients in the usual care group who did not receive invasive mechanical ventilation at the start of the study compared with those in dexamethasone group were more likely to progress to the secondary outcome of invasive mechanical ventilation or death (risk ratio, 0.92; 95% CI, 0.84-1.01).
Researchers concluded that while their preliminary results provide evidence that dexamethasone may reduce 28-day mortality in patients with COVID-19 who receive respiratory support, they found no benefit (and the possibility of harm) in patients who did not require oxygen.
The RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19—preliminary report [published online July 17, 2020]. N Engl J Med. doi:10.1056/NEJMoa2021436