Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance

DOI record: { "DOI": "10.1016/j.ijantimicag.2021.106428", "ISSN": [ "0924-8579" ], "URL": "http://dx.doi.org/10.1016/j.ijantimicag.2021.106428", "alternative-id": [ "S0924857921002065" ], "article-number": "106428", "assertion": [ { "label": "This article is maintained by", "name": "publisher", "value": "Elsevier" }, { "label": "Article Title", "name": "articletitle", "value": "Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance" }, { "label": "Journal Title", "name": "journaltitle", "value": "International Journal of Antimicrobial Agents" }, { "label": "CrossRef DOI link to publisher maintained version", "name": "articlelink", "value": "https://doi.org/10.1016/j.ijantimicag.2021.106428" }, { "label": "Content Type", "name": "content_type", "value": "article" }, { "label": "Copyright", "name": "copyright", "value": "© 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved." } ], "author": [ { "ORCID": "http://orcid.org/0000-0002-5002-0953", "affiliation": [], "authenticated-orcid": false, "family": "Rodrigues", "given": "Cristhieni", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0002-4604-4549", "affiliation": [], "authenticated-orcid": false, "family": "Freitas-Santos", "given": "Rodrigo S.", "sequence": "additional" }, { "affiliation": [], "family": "Levi", "given": "José Eduardo", "sequence": "additional" }, { "affiliation": [], "family": "Senerchia", "given": "Andreza A.", "sequence": "additional" }, { "affiliation": [], "family": "Lopes", "given": "Ana Tarina A.", "sequence": "additional" }, { "affiliation": [], "family": "Santos", "given": "Sergio R.", "sequence": "additional" }, { "affiliation": [], "family": "Siciliano", "given": "Rinaldo F.", "sequence": "additional" }, { "affiliation": [], "family": "Pierrotti", "given": "Lígia C.", "sequence": "additional" } ], "container-title": "International Journal of Antimicrobial Agents", "container-title-short": "International Journal of Antimicrobial Agents", "content-domain": { "crossmark-restriction": true, "domain": [ "clinicalkey.jp", "clinicalkey.com", "clinicalkey.es", "clinicalkey.com.au", "clinicalkey.fr", "elsevier.com", "sciencedirect.com" ] }, "created": { "date-parts": [ [ 2021, 8, 25 ] ], "date-time": "2021-08-25T15:20:06Z", "timestamp": 1629904806000 }, "deposited": { "date-parts": [ [ 2021, 10, 25 ] ], "date-time": "2021-10-25T16:10:32Z", "timestamp": 1635178232000 }, "indexed": { "date-parts": [ [ 2024, 1, 22 ] ], "date-time": "2024-01-22T11:39:47Z", "timestamp": 1705923587338 }, "is-referenced-by-count": 10, "issue": "5", "issued": { "date-parts": [ [ 2021, 11 ] ] }, "journal-issue": { "issue": "5", "published-print": { "date-parts": [ [ 2021, 11 ] ] } }, "language": "en", "license": [ { "URL": "https://www.elsevier.com/tdm/userlicense/1.0/", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 11, 1 ] ], "date-time": "2021-11-01T00:00:00Z", "timestamp": 1635724800000 } } ], "link": [ { "URL": "https://api.elsevier.com/content/article/PII:S0924857921002065?httpAccept=text/xml", "content-type": "text/xml", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://api.elsevier.com/content/article/PII:S0924857921002065?httpAccept=text/plain", "content-type": "text/plain", "content-version": "vor", "intended-application": "text-mining" } ], "member": "78", "original-title": [], "page": "106428", "prefix": "10.1016", "published": { "date-parts": [ [ 2021, 11 ] ] }, "published-print": { "date-parts": [ [ 2021, 11 ] ] }, "publisher": "Elsevier BV", "reference": [ { "key": "10.1016/j.ijantimicag.2021.106428_bib0001", "unstructured": "Organization GWH. WHO coronavirus disease (COVID-19) dashboard. Available at: https://covid19.who.int/[accessed 07 June 2021 ]." }, { "DOI": "10.5582/ddt.2020.01012", "article-title": "Discovering drugs to treat coronavirus disease 2019 (COVID-19)", "author": "Dong", "doi-asserted-by": "crossref", "first-page": "58", "issue": "1", "journal-title": "Drug Discov Ther", "key": "10.1016/j.ijantimicag.2021.106428_bib0002", "volume": "14", "year": "2020" }, { "DOI": "10.1038/s41421-019-0132-8", "article-title": "Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "author": "Liu", "doi-asserted-by": "crossref", "first-page": "1", "issue": "1", "journal-title": "Cell Disc", "key": "10.1016/j.ijantimicag.2021.106428_bib0003", "volume": "6", "year": "2020" }, { "DOI": "10.1016/j.ijantimicag.2020.105949", "article-title": "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial", "author": "Gautret", "doi-asserted-by": "crossref", "issue": "1", "journal-title": "Int J Antimicrob Agents", "key": "10.1016/j.ijantimicag.2021.106428_bib0004", "volume": "56", "year": "2020" }, { "DOI": "10.1038/s41422-020-0282-0", "article-title": "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "269", "issue": "3", "journal-title": "Cell Res", "key": "10.1016/j.ijantimicag.2021.106428_bib0005", "volume": "30", "year": "2020" }, { "article-title": "In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication", "author": "Touret", "first-page": "1", "issue": "1", "journal-title": "Sci Reports", "key": "10.1016/j.ijantimicag.2021.106428_bib0006", "volume": "10", "year": "2020" }, { "DOI": "10.1002/cpt.1857", "article-title": "Clinical pharmacology perspectives on the antiviral activity of azithromycin and use in COVID-19", "author": "Damle", "doi-asserted-by": "crossref", "first-page": "201", "issue": "2", "journal-title": "Clin Pharmacol Therapeut", "key": "10.1016/j.ijantimicag.2021.106428_bib0007", "volume": "108", "year": "2020" }, { "DOI": "10.3389/fimmu.2018.00302", "article-title": "The immunomodulatory effects of macrolides—a systematic review of the underlying mechanisms", "author": "Zimmermann", "doi-asserted-by": "crossref", "first-page": "302", "journal-title": "Front Immunol", "key": "10.1016/j.ijantimicag.2021.106428_bib0008", "volume": "9", "year": "2018" }, { "DOI": "10.1093/cid/ciaa1009", "article-title": "Hydroxychloroquine for early treatment of adults with mild Covid-19: a randomized-controlled trial", "author": "Mitjà", "doi-asserted-by": "crossref", "first-page": "ciaa1009", "journal-title": "Clin Infect Dis", "key": "10.1016/j.ijantimicag.2021.106428_bib0009", "volume": "2000", "year": "2020" }, { "article-title": "Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial", "author": "Tang", "first-page": "369", "journal-title": "BMJ", "key": "10.1016/j.ijantimicag.2021.106428_bib0010", "year": "2020" }, { "DOI": "10.1056/NEJMoa2012410", "article-title": "Observational study of hydroxychloroquine in hospitalized patients with Covid-19", "author": "Geleris", "doi-asserted-by": "crossref", "first-page": "2411", "issue": "25", "journal-title": "N Eng J Med", "key": "10.1016/j.ijantimicag.2021.106428_bib0011", "volume": "382", "year": "2020" }, { "DOI": "10.1001/jama.2020.8630", "article-title": "Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State", "author": "Rosenberg", "doi-asserted-by": "crossref", "first-page": "2493", "issue": "24", "journal-title": "JAMA", "key": "10.1016/j.ijantimicag.2021.106428_bib0012", "volume": "323", "year": "2020" }, { "DOI": "10.1056/NEJMoa2019014", "article-title": "Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19", "author": "Cavalcanti", "doi-asserted-by": "crossref", "first-page": "2041", "issue": "21", "journal-title": "N Eng J Med", "key": "10.1016/j.ijantimicag.2021.106428_bib0013", "volume": "383", "year": "2020" }, { "article-title": "No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial", "author": "Mahevas", "journal-title": "Medrxiv", "key": "10.1016/j.ijantimicag.2021.106428_bib0014", "year": "2020" }, { "DOI": "10.1016/j.tmaid.2020.101738", "article-title": "Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France", "author": "Million", "doi-asserted-by": "crossref", "journal-title": "Travel Med Infect Dis", "key": "10.1016/j.ijantimicag.2021.106428_bib0015", "volume": "35", "year": "2020" }, { "key": "10.1016/j.ijantimicag.2021.106428_bib0016", "unstructured": "Trial R. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. Press release from the chief investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial (https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19). 2020 [last accessed 07 Jun 2021]." }, { "article-title": "A systematic review and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azithromycin in COVID-19 treatment", "author": "Ghazy", "first-page": "1", "issue": "1", "journal-title": "Sci Reports", "key": "10.1016/j.ijantimicag.2021.106428_bib0017", "volume": "10", "year": "2020" }, { "key": "10.1016/j.ijantimicag.2021.106428_bib0018", "unstructured": "ClinicalTrials.gov. ClinicalTrials.gov “Basic Results” Data Element Definitions. 2013. Available at: http://prsinfo.clinicaltrials.gov/results_definitions.html#AdverseEventsDefinition). [accessed 07 June 2021]." }, { "DOI": "10.1016/j.jbi.2019.103208", "article-title": "The REDCap consortium: Building an international community of software platform partners", "author": "Harris", "doi-asserted-by": "crossref", "journal-title": "J Biomed Informatics", "key": "10.1016/j.ijantimicag.2021.106428_bib0019", "volume": "95", "year": "2019" }, { "author": "Team", "key": "10.1016/j.ijantimicag.2021.106428_bib0020", "series-title": "R: A language and environment for statistical computing", "year": "2013" }, { "DOI": "10.2307/2531201", "article-title": "Evaluation of sample size and power for analyses of survival with allowance for nonuniform patient entry, losses to follow-up, noncompliance, and stratification", "author": "Lachin", "doi-asserted-by": "crossref", "first-page": "507", "journal-title": "Biometrics", "key": "10.1016/j.ijantimicag.2021.106428_bib0021", "year": "1986" }, { "DOI": "10.2807/1560-7917.ES.2020.25.3.2000045", "article-title": "Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR", "author": "Corman", "doi-asserted-by": "crossref", "issue": "3", "journal-title": "Eurosurveillance", "key": "10.1016/j.ijantimicag.2021.106428_bib0022", "volume": "25", "year": "2020" }, { "DOI": "10.1002/cpt.1993", "article-title": "Pharmacokinetics and Pharmacological Properties of Chloroquine and Hydroxychloroquine in the Context of COVID-19 Infection", "author": "Nicol", "doi-asserted-by": "crossref", "first-page": "1135", "issue": "6", "journal-title": "Clin Pharmacol Therapeut", "key": "10.1016/j.ijantimicag.2021.106428_bib0023", "volume": "108", "year": "2020" }, { "DOI": "10.1093/cid/ciaa237", "article-title": "In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)", "author": "Yao", "doi-asserted-by": "crossref", "first-page": "732", "issue": "15", "journal-title": "Clin Infect Dis", "key": "10.1016/j.ijantimicag.2021.106428_bib0024", "volume": "71", "year": "2020" }, { "DOI": "10.1093/cid/ciaa394", "article-title": "Towards optimization of hydroxychloroquine dosing in intensive care unit COVID-19 patients", "author": "Perinel", "doi-asserted-by": "crossref", "first-page": "2227", "issue": "16", "journal-title": "Clin Infect Dis", "key": "10.1016/j.ijantimicag.2021.106428_bib0025", "volume": "71", "year": "2020" }, { "DOI": "10.1056/NEJMoa2016638", "article-title": "A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19", "author": "Boulware", "doi-asserted-by": "crossref", "first-page": "517", "issue": "6", "journal-title": "N Eng J Med", "key": "10.1016/j.ijantimicag.2021.106428_bib0026", "volume": "383", "year": "2020" }, { "DOI": "10.1016/S1473-3099(20)30296-6", "article-title": "Chloroquine or hydroxychloroquine for prophylaxis of COVID-19", "author": "Principi", "doi-asserted-by": "crossref", "first-page": "1118", "issue": "10", "journal-title": "Lancet Infect Dis", "key": "10.1016/j.ijantimicag.2021.106428_bib0027", "volume": "20", "year": "2020" } ], "reference-count": 27, "references-count": 27, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S0924857921002065" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Pharmacology (medical)", "Infectious Diseases", "Microbiology (medical)", "General Medicine" ], "subtitle": [], "title": "Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy", "volume": "58" }