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

Huimin Wu; Salim Daouk; Jad Kebbe; Fawad Chaudry; Jarrod Harper; Brent Brown

Abstract: Citation: WuH, Daouk S, Kebbe J, Chaudry F, Harper J, Brown B (2022) Low-dose versus highdose dexamethasone for hospitalized patients with COVID-19 pneumonia: A randomized clinical trial. PLoS ONE 17(10): e0275217. https://doi.org/ 10.1371/journal.pone.0275217 Editor: Davor Plavec, Srebrnjak Children's Hospital, CROATIA Received: July 11, 2022 Accepted: September 9, 2022 Published: October 3, 2022 Copyright: © 2022 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. 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 RESEARCHARTICLE Low-dose versus high-dose dexamethasone for hospitalized patients with COVID-19 pneumonia: A randomized clinical trial Huimin WuID 1 * , Salim DaoukID 1 , Jad Kebbe 1 , Fawad Chaudry 1 , Jarrod Harper 2 , Brent Brown 1 1 Pulmonary, Critical Care and Sleep Medicine Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 2 College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America * Huimin-Wu@ouhsc.edu 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 mgdaily vs. 20 mg daily of dexamethasone in hospitalized patients with COVID-19 pneumonia. Methods Weconducted 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 highflow oxygen or noninvasive ventilation at randomization received immune modulators. did not support authors' salary. There was no additional external funding received for this study. Competing interests: The authors have declared that no..

DOI record: { "DOI": "10.1371/journal.pone.0275217", "ISSN": [ "1932-6203" ], "URL": "http://dx.doi.org/10.1371/journal.pone.0275217", "abstract": "\nBackground\nDexamethasone 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.\n\n\nMethods\nWe 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.\n\n\nResults\nOf 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.\n\n\nConclusions\nDexamethasone 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.\n\n\nTrial registration\nClinialtrials.gov number, NCT04707534, registered January 13, 2021\n", "author": [ { "ORCID": "https://orcid.org/0000-0001-7023-8362", "affiliation": [], "authenticated-orcid": true, "family": "Wu", "given": "Huimin", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0002-9427-6504", "affiliation": [], "authenticated-orcid": true, "family": "Daouk", "given": "Salim", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Kebbe", "given": "Jad", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Chaudry", "given": "Fawad", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Harper", "given": "Jarrod", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Brown", "given": "Brent", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" } ], "container-title": "PLOS ONE", "container-title-short": "PLoS ONE", "content-domain": { "crossmark-restriction": false, "domain": [ "www.plosone.org" ] }, "created": { "date-parts": [ [ 2022, 10, 3 ] ], "date-time": "2022-10-03T17:47:20Z", "timestamp": 1664819240000 }, "deposited": { "date-parts": [ [ 2022, 10, 3 ] ], "date-time": "2022-10-03T17:47:56Z", "timestamp": 1664819276000 }, "editor": [ { "affiliation": [], "family": "Plavec", "given": "Davor", "role": [ { "role": "editor", "vocabulary": "crossref" } ], "sequence": "first" } ], "funder": [ { "DOI": "10.13039/100007927", "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100007927", "id-type": "DOI" } ], "name": "University of Oklahoma Health Sciences Center" } ], "indexed": { "date-parts": [ [ 2026, 3, 5 ] ], "date-time": "2026-03-05T11:52:53Z", "timestamp": 1772711573423, "version": "3.50.1" }, "is-referenced-by-count": 35, "issue": "10", "issued": { "date-parts": [ [ 2022, 10, 3 ] ] }, "journal-issue": { "issue": "10", "published-online": { "date-parts": [ [ 2022, 10, 3 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 10, 3 ] ], "date-time": "2022-10-03T00:00:00Z", "timestamp": 1664755200000 } } ], "link": [ { "URL": "https://dx.plos.org/10.1371/journal.pone.0275217", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "340", "original-title": [], "page": "e0275217", "prefix": "10.1371", "published": { "date-parts": [ [ 2022, 10, 3 ] ] }, "published-online": { "date-parts": [ [ 2022, 10, 3 ] ] }, "publisher": "Public Library of Science (PLoS)", "reference": [ { "author": "Infectious Diseases Society of America.", "journal-title": "IDSA Guidelines on the Treatment and Management of Patients with COVID-19", "key": "pone.0275217.ref001", "year": "2022" }, { "article-title": "Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19", "author": "WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.", "first-page": "1330", "issue": "13", "journal-title": "A Meta-analysis. 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