Effect of early administration of dexamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome: EARLY-DEX COVID-19 trial

{ 'indexed': {'date-parts': [[2024, 7, 19]], 'date-time': '2024-07-19T00:24:31Z', 'timestamp': 1721348671372}, 'reference-count': 25, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2024, 7, 17]], 'date-time': '2024-07-17T00:00:00Z', 'timestamp': 1721174400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:sec><jats:title>Introduction and objectives</jats:title><jats:p>Corticosteroids are ' 'among the drugs demonstrating a mortality benefit for coronavirus disease 2019 (COVID-19). ' 'The RECOVERY trial highlighted that dexamethasone reduced 28-day mortality for hospitalized ' 'COVID-19 patients requiring either supplemental oxygen or mechanical ventilation. It is noted ' 'that approximately 30% of COVID-19 patients, initially presenting with mild symptoms, will ' 'advance to acute respiratory distress syndrome (ARDS), especially those with detectable ' 'laboratory markers of inflammation indicative of disease progression. Our research aimed to ' 'explore the efficacy of dexamethasone in preventing the progression to ARDS in patients ' 'hospitalized with COVID-19 pneumonia who do not yet require additional oxygen but are at high ' 'risk of developing ARDS, potentially leading to a reduction in ' 'morbimortality.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this ' 'multicenter, randomized, controlled trial, we evaluated the impact of dexamethasone on adult ' 'patients diagnosed with COVID-19 pneumonia who did not need supplementary oxygen at admission ' 'but were identified as having risk factors for ARDS. The risk of ARDS was determined based on ' 'specific criteria: elevated lactate dehydrogenase levels over 245\u2009U/L, C-reactive ' 'protein levels exceeding 100\u2009mg/L, and a lymphocyte count below 0.80 × ' '10<jats:sup>9</jats:sup>/L. Participants were randomly allocated to either receive ' 'dexamethasone or the standard care. The primary endpoints included the incidence of moderate ' 'or severe ARDS and all-cause mortality within 30\u2009days ' 'post-enrollment.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>One ' 'hundred twenty-six patients were randomized. Among them, 41 were female (30.8%), with a mean ' 'age of 48.8\u2009±\u200914.4\u2009years. Ten patients in the dexamethasone group (17.2%) and ' 'ten patients in the control group (14.7%) developed moderate ARDS with no significant ' 'differences. Mechanical ventilation was required in six patients (4.7%), with four in the ' 'treatment group and two in the control group. There were no deaths during hospitalization or ' 'during follow-up. An intermediate analysis for futility showed some differences between the ' 'control and treatment groups (Z\u2009=\u20090.0284). However, these findings were within the ' 'margins close to the region where the null hypothesis would not be ' 'rejected.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In patients ' 'with COVID-19 pneumonia without oxygen needs but at risk of progressing to severe disease, ' 'early dexamethasone administration did not lead to a decrease in ARDS ' 'development.</jats:p></jats:sec><jats:sec><jats:title>Clinical trial ' 'registration</jats:title><jats:p><jats:ext-link>ClinicalTrials.gov</jats:ext-link>, ' 'identifier NCT04836780.</jats:p></jats:sec>', 'DOI': '10.3389/fmed.2024.1385833', 'type': 'journal-article', 'created': {'date-parts': [[2024, 7, 18]], 'date-time': '2024-07-18T12:37:50Z', 'timestamp': 1721306270000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Effect of early administration of dexamethasone in patients with COVID-19 pneumonia without ' 'acute hypoxemic respiratory 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'article-title': 'Cytokine Storm', 'volume': '383', 'author': 'Fajgenbaum', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'key': 'ref3', 'doi-asserted-by': 'publisher', 'first-page': '607', 'DOI': '10.1016/j.jinf.2020.03.037', 'article-title': "The pathogenesis and treatment of the `cytokine Storm' in COVID-19", 'volume': '80', 'author': 'Ye', 'year': '2020', 'journal-title': 'J Infect'}, {'key': 'ref4', 'year': ''}, {'key': 'ref5', 'year': '2021'}, { 'key': 'ref6', 'doi-asserted-by': 'publisher', 'first-page': 'n526', 'DOI': '10.1136/bmj.n526', 'article-title': 'A living WHO guideline on drugs to prevent covid-19', 'volume': '372', 'author': 'Lamontagne', 'year': '2021', 'journal-title': 'BMJ'}, { 'key': 'ref7', 'doi-asserted-by': 'publisher', 'first-page': '693', 'DOI': '10.1056/NEJMoa2021436', 'article-title': 'Dexamethasone in hospitalized patients with Covid-19', 'volume': '384', 'author': 'Horby', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': 'ref8', 'doi-asserted-by': 'publisher', 'first-page': '1330', 'DOI': '10.1001/jama.2020.17023', 'article-title': 'Association between Administration of Systemic Corticosteroids and ' 'Mortality among Critically ill Patients with COVID-19: a Meta-analysis', 'volume': '324', 'author': 'JAC', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': 'ref9', 'doi-asserted-by': 'publisher', 'first-page': '30', 'DOI': '10.1186/s40001-020-00432-3', 'article-title': 'Laboratory features of severe vs. non-severe COVID-19 patients in Asian ' 'populations: a systematic review and meta-analysis', 'volume': '25', 'author': 'Ghahramani', 'year': '2020', 'journal-title': 'Eur J Med Res'}, { 'key': 'ref10', 'doi-asserted-by': 'publisher', 'first-page': 'e23315', 'DOI': '10.1097/MD.0000000000023315', 'article-title': 'Association of elevated inflammatory markers and severe COVID-19: a ' 'meta-analysis', 'volume': '99', 'author': 'Ji', 'year': '2020', 'journal-title': 'Medicine (Baltimore)'}, { 'key': 'ref11', 'doi-asserted-by': 'publisher', 'first-page': '1239', 'DOI': '10.1001/jama.2020.2648', 'article-title': 'Characteristics of and important lessons from the coronavirus disease ' '2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases ' 'from the Chinese Center for Disease Control and Prevention', 'volume': '323', 'author': 'Wu', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': 'ref12', 'doi-asserted-by': 'publisher', 'first-page': '389', 'DOI': '10.1080/10408363.2020.1770685', 'article-title': 'Biomarkers associated with COVID-19 disease progression', 'volume': '57', 'author': 'Ponti', 'year': '2020', 'journal-title': 'Crit Rev Clin Lab Sci'}, { 'key': 'ref13', 'doi-asserted-by': 'publisher', 'first-page': '422', 'DOI': '10.1136/postgradmedj-2020-139542', 'article-title': 'Prognostic value of elevated lactate dehydrogenase in patients with ' 'COVID-19: a systematic review and meta-analysis', 'volume': '98', 'author': 'Martha', 'year': '2022', 'journal-title': 'Postgrad Med J'}, { 'key': 'ref14', 'doi-asserted-by': 'publisher', 'first-page': '869', 'DOI': '10.1515/jom-2021-0103', 'article-title': 'C-reactive protein levels associated with COVID-19 outcomes in the ' 'United States', 'volume': '121', 'author': 'Lentner', 'year': '2021', 'journal-title': 'J Osteopath Med'}, { 'key': 'ref15', 'doi-asserted-by': 'publisher', 'first-page': '55', 'DOI': '10.1186/s12890-021-01422-9', 'article-title': 'Association between peripheral lymphocyte count and the mortality risk ' 'of COVID-19 inpatients', 'volume': '21', 'author': 'Wang', 'year': '2021', 'journal-title': 'BMC Pulm Med'}, { 'key': 'ref16', 'doi-asserted-by': 'publisher', 'first-page': '784', 'DOI': '10.1186/s13063-022-06722-x', 'article-title': 'Effect of EARLY administration of DEXamethasone in patients with ' 'COVID-19 pneumonia without acute hypoxemic respiratory failure and risk ' 'of development of acute respiratory distress syndrome (EARLY-DEX ' 'COVID-19): study protocol for a randomized controlled trial', 'volume': '23', 'author': 'Franco-Moreno', 'year': '2022', 'journal-title': 'Trials'}, { 'key': 'ref17', 'doi-asserted-by': 'publisher', 'first-page': '2191', 'DOI': '10.1001/jama.2013.281053', 'article-title': 'World medical association declaration of Helsinki: ethical principles ' 'for medical research involving human subjects', 'volume': '310', 'year': '2013', 'journal-title': 'JAMA'}, {'key': 'ref18', 'year': ''}, {'key': 'ref19', 'year': ''}, { 'key': 'ref20', 'doi-asserted-by': 'publisher', 'first-page': '2526', 'DOI': '10.1001/jama.2012.5669', 'article-title': 'Acute respiratory distress syndrome: the Berlin Definition', 'volume': '307', 'author': 'Definition Task Force', 'year': '2012', 'journal-title': 'JAMA'}, { 'key': 'ref21', 'doi-asserted-by': 'publisher', 'first-page': '116', 'DOI': '10.1159/000512063', 'article-title': 'Early use of corticosteroid may prolong SARS-CoV-2 shedding in ' 'non-intensive care unit patients with COVID-19 pneumonia: a ' 'multicenter, single-blind, randomized control trial', 'volume': '100', 'author': 'Tang', 'year': '2021', 'journal-title': 'Respiration'}, { 'key': 'ref22', 'doi-asserted-by': 'publisher', 'first-page': '2100048', 'DOI': '10.1183/13993003.00048-2021', 'article-title': 'Management of hospitalised adults with coronavirus disease 2019 ' '(COVID-19): a European Respiratory Society living guideline', 'volume': '57', 'author': 'Chalmers', 'year': '2021', 'journal-title': 'Eur Respir J'}, { 'key': 'ref23', 'doi-asserted-by': 'publisher', 'first-page': 'e238516', 'DOI': '10.1001/jamanetworkopen.2023.8516', 'article-title': 'Dexamethasone for inpatients with COVID-19 in a National Cohort', 'volume': '6', 'author': 'Mourad', 'year': '2023', 'journal-title': 'JAMA Netw Open'}, { 'key': 'ref24', 'doi-asserted-by': 'publisher', 'first-page': '807981', 'DOI': '10.3389/fmed.2022.807981', 'article-title': 'Methylprednisolone pulses in hospitalized COVID-19 patients without ' 'respiratory failure: a randomized controlled trial', 'volume': '9', 'author': 'Les', 'year': '2022', 'journal-title': 'Front Med (Lausanne)'}, { 'key': 'ref25', 'doi-asserted-by': 'publisher', 'first-page': '273', 'DOI': '10.5582/ddt.2021.01081', 'article-title': 'Role of systemic corticosteroids in preventing hypoxia among patients ' 'with mild COVID-19: an observational study', 'volume': '15', 'author': 'Aggarwal', 'year': '2021', 'journal-title': 'Drug Discov Ther'}], 'container-title': 'Frontiers in Medicine', 'original-title': [], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2024.1385833/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 7, 18]], 'date-time': '2024-07-18T12:37:54Z', 'timestamp': 1721306274000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2024.1385833/full'}}, 'subtitle': [], 'short-title': [], 'issued': 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