Low-dose versus high-dose dexamethasone for hospitalized patients with COVID-19 pneumonia: A randomized clinical trial

PLoS One. 2022 Oct 3;17(10):e0275217. doi: 10.1371/journal.pone.0275217. eCollection 2022.

Abstract

Background: Dexamethasone 6 mg daily for 10 days is the recommended treatment for patients with severe or critical coronavirus disease 2019 (COVID-19). The evidence on the benefit of high-dose dexamethasone is limited. The goal of this study was to assess the effects of 6 mg daily vs. 20 mg daily of dexamethasone in hospitalized patients with COVID-19 pneumonia.

Methods: We conducted a single-center, randomized, clinical trial involving hospitalized patients with COVID-19 pneumonia. Participants were randomized 1:1 to dexamethasone 6 mg daily or dexamethasone 20 mg daily, and were stratified by the WHO-Ordinal Scale for Clinical Improvement (OSCI). The primary outcome was clinical improvement equal to or greater than 2 points by OSCI on day 28. Secondary outcomes were 28-day mortality, intensive care unit-free days, and ventilator-free days on day 28.

Results: Of the 107 patients who enrolled and completed the follow up, 55 patients enrolled in the low-dose group and 52 patients enrolled in the high-dose group. Treatment with dexamethasone 20 mg daily compared with dexamethasone 6 mg daily did not result in better clinical improvement based on OSCI on day 28 (71.2% vs. 78.2%; odds ratio, 1.45 [0.55-3.86]; p = 0.403). For participants who required high-flow oxygen or noninvasive ventilation at randomization, the 6-mg group had better survival than the 20-mg group on day 28 (100% vs. 57.1%; p = 0.025). Although more participants in the 6-mg group received immune modulators (40% vs. 21.2%; p = 0.035), 50% of death cases in the 20-mg group who required high-flow oxygen or noninvasive ventilation at randomization received immune modulators.

Conclusions: Dexamethasone 20 mg daily did not result in better clinical outcome improvement, and was probably associated with higher 28-day mortality in patients on high-flow oxygen or noninvasive ventilation, compared with dexamethasone 6 mg daily.

Trial registration: Clinialtrials.gov number, NCT04707534, registered January 13, 2021.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 Drug Treatment*
  • Dexamethasone / therapeutic use
  • Humans
  • Oxygen
  • SARS-CoV-2

Substances

  • Dexamethasone
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT04707534

Grants and funding

This study was supported by the University of Oklahoma Health Sciences Center COVID-19 research grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The grant supported the research staff salary and research equipment and supplies, but did not support authors' salary. There was no additional external funding received for this study.