Dexamethasone in Hospitalized COVID-19 Patients

Aug 03, 2020
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Authors:
The RECOVERY Collaborative Group.
Citation:
Dexamethasone in Hospitalized Patients With Covid-19 — Preliminary Report. N Engl J Med 2020;Jul 17:[Epub ahead of print].
Summary By:
Rachel Eshima McKay, MD

Quick Takes

  • The RECOVERY trial is a large-scale effort to rapidly assess possible effectiveness of existing medications to reduce mortality in patients hospitalized with COVID-19 in the United Kingdom.
  • Preliminary findings from the substudy of dexamethasone versus standard medical care were published, showing apparent mortality benefit of patients receiving dexamethasone compared to standard medical care.
  • Subgroup analysis by initial symptom severity suggests that predominant benefit from dexamethasone was derived by patients already requiring supplemental oxygen or invasive ventilatory support at the time of enrollment.

Study Questions:

Does use of dexamethasone decrease mortality among patients hospitalized with coronavirus disease 2019 (COVID-19) infection?

Methods:

Patients hospitalized with COVID-19 across 176 National Health Service organizations in the United Kingdom were enrolled in the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, a controlled, open-label randomized study evaluating the possible impact of one of four different medications (dexamethasone, hydroxychloroquine, lopinavir-ritonavir, or azithromycin) on outcome. In the dexamethasone study, participants were randomized to receive dexamethasone 6 mg daily, for 10 days or until time of hospital discharge if discharged (whichever occurred first), versus standard medical care. The primary outcome was all-cause mortality within 28 days of randomization, and secondary outcomes included time to hospital discharge and rates of progression to ventilatory dependency during the study period among patients not requiring invasive ventilatory support at time of randomization. Analysis was by intention-to-treat.

Results:

  • 11,303 patients were randomized to the RECOVERY trial between March 19 and June 8, 2020, among whom 6,425 participated in the dexamethasone study.
  • Of these 6,425, 2,104 were randomized to dexamethasone, and 4,321 were assigned to receive usual care.
  • Between-group mortality difference varied significantly according to dependency on respiratory support (supplemental oxygen or mechanical ventilation) at the time of randomization.
  • In the overall study population, death occurred in 482 of 2,104 (22.9%) patients assigned to receive dexamethasone versus 1,110 of 4,321 (25.7%) assigned to standard care (rate ratio, 0.83 [0.75-0.93]).
  • In patients receiving invasive mechanical ventilation at the time of randomization, the outcome difference was more pronounced, with death occurring in 29.3% of patients receiving dexamethasone versus 41.4% with standard care (rate ratio, 0.61 [95% confidence interval, 0.51-0.81]).
  • In patients requiring supplemental oxygen (± noninvasive ventilatory support) at the time of randomization, death occurred in 23.3% receiving dexamethasone versus 26.2% receiving standard care (rate ratio, 0.82 [0.72-0.94]).
  • In patients receiving neither supplemental oxygen nor ventilatory support at the time of randomization, all-cause mortality did not differ significantly according to randomization, occurring in 17.8% receiving dexamethasone versus 14.0% receiving standard care (rate ratio, 1.19 [0.91-1.55]).
  • Patients in the dexamethasone arm had shorter hospitalization (median 12 vs. 13 days), greater chance of remaining alive until discharge (rate ratio, 1.10 [1.03-1.17]), and lower risk of subsequent need for invasive mechanical ventilation (risk ratio, 0.92 [0.84-1.01]) compared to patients in the standard care group.

Conclusions:

These preliminary findings indicate that among patients hospitalized with COVID-19, a protocol of 6 mg daily dexamethasone resulted in lesser risk of death among individuals requiring supplemental oxygen and/or ventilatory support compared to standard care.

Perspective:

The principal benefit of dexamethasone in patients with severe symptoms of COVID-19 is thought to occur by mitigating the process of inflammatory-mediated lung injury; this mechanism of action would explain the apparent relationship between symptom severity and probability of clinically beneficial response for patients in the RECOVERY study. However, these preliminary findings will require further analysis to determine possible benefits or harms of dexamethasone for patients with early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who have not progressed to needing supplemental oxygen or ventilatory support.

Clinical Topics: COVID-19 Hub, Prevention, Novel Agents, Statins

Keywords: Azithromycin, Coronavirus, COVID-19, Dexamethasone, Hydroxychloroquine, Inflammation, Length of Stay, Lopinavir, Lung Injury, Patient Discharge, Primary Prevention, Respiration, Artificial, Ritonavir, severe acute respiratory syndrome coronavirus 2, Ventilators, Mechanical


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