COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients

DOI record: { "DOI": "10.1371/journal.pone.0248128", "ISSN": [ "1932-6203" ], "URL": "http://dx.doi.org/10.1371/journal.pone.0248128", "abstract": "<jats:sec id=\"sec001\">\n<jats:title>Background</jats:title>\n<jats:p>The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods</jats:title>\n<jats:p>Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results</jats:title>\n<jats:p>Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion</jats:title>\n<jats:p>Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.</jats:p>\n</jats:sec>", "author": [ { "affiliation": [], "family": "Stewart", "given": "Mark", "sequence": "first" }, { "affiliation": [], "family": "Rodriguez-Watson", "given": "Carla", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6436-3164", "affiliation": [], "authenticated-orcid": true, "family": "Albayrak", "given": "Adem", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-8991-3276", "affiliation": [], "authenticated-orcid": true, "family": "Asubonteng", "given": "Julius", "sequence": "additional" }, { "affiliation": [], "family": "Belli", "given": "Andrew", "sequence": "additional" }, { "affiliation": [], "family": "Brown", "given": "Thomas", "sequence": "additional" }, { "affiliation": [], "family": "Cho", "given": "Kelly", "sequence": "additional" }, { "affiliation": [], "family": "Das", "given": "Ritankar", "sequence": "additional" }, { "affiliation": [], "family": "Eldridge", "given": "Elizabeth", "sequence": "additional" }, { "affiliation": [], "family": "Gatto", "given": "Nicolle", "sequence": "additional" }, { "affiliation": [], "family": "Gelman", "given": "Alice", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6700-2129", "affiliation": [], "authenticated-orcid": true, "family": "Gerlovin", "given": "Hanna", "sequence": "additional" }, { "affiliation": [], "family": "Goldberg", "given": "Stuart L.", "sequence": "additional" }, { "affiliation": [], "family": "Hansen", "given": "Eric", "sequence": "additional" }, { "affiliation": [], "family": "Hirsch", "given": "Jonathan", "sequence": "additional" }, { "affiliation": [], "family": "Ho", "given": "Yuk-Lam", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-0456-5618", "affiliation": [], "authenticated-orcid": true, "family": "Ip", "given": "Andrew", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-1852-5342", "affiliation": [], "authenticated-orcid": true, "family": "Izano", "given": "Monika", "sequence": "additional" }, { "affiliation": [], "family": "Jones", "given": "Jason", "sequence": "additional" }, { "affiliation": [], "family": "Justice", "given": "Amy C.", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-2095-3661", "affiliation": [], "authenticated-orcid": true, "family": "Klesh", "given": "Reyna", "sequence": "additional" }, { "affiliation": [], "family": "Kuranz", "given": "Seth", "sequence": "additional" }, { "affiliation": [], "family": "Lam", "given": "Carson", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-6001-6723", "affiliation": [], "authenticated-orcid": true, "family": "Mao", "given": "Qingqing", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-3146-2243", "affiliation": [], "authenticated-orcid": true, "family": "Mataraso", "given": "Samson", "sequence": "additional" }, { "affiliation": [], "family": "Mera", "given": "Robertino", "sequence": "additional" }, { "affiliation": [], "family": "Posner", "given": "Daniel C.", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-4369-7381", "affiliation": [], "authenticated-orcid": true, "family": "Rassen", "given": "Jeremy A.", "sequence": "additional" }, { "affiliation": [], "family": "Siefkas", "given": "Anna", "sequence": "additional" }, { "affiliation": [], "family": "Schrag", "given": "Andrew", "sequence": "additional" }, { "affiliation": [], "family": "Tourassi", "given": "Georgia", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6227-6796", "affiliation": [], "authenticated-orcid": true, "family": "Weckstein", "given": "Andrew", "sequence": "additional" }, { "affiliation": [], "family": "Wolf", "given": "Frank", "sequence": "additional" }, { "affiliation": [], "family": "Bhat", "given": "Amar", "sequence": "additional" }, { "affiliation": [], "family": "Winckler", "given": "Susan", "sequence": "additional" }, { "affiliation": [], "family": "Sigal", "given": "Ellen V.", "sequence": "additional" }, { "affiliation": [], "family": "Allen", "given": "Jeff", "sequence": "additional" } ], "container-title": "PLOS ONE", "container-title-short": "PLoS ONE", "content-domain": { "crossmark-restriction": false, "domain": [ "www.plosone.org" ] }, "created": { "date-parts": [ [ 2021, 3, 17 ] ], "date-time": "2021-03-17T17:51:06Z", "timestamp": 1616003466000 }, "deposited": { "date-parts": [ [ 2021, 3, 17 ] ], "date-time": "2021-03-17T17:51:29Z", "timestamp": 1616003489000 }, "editor": [ { "affiliation": [], "family": "Di Gennaro", "given": "Francesco", "sequence": "first" } ], "indexed": { "date-parts": [ [ 2024, 3, 26 ] ], "date-time": "2024-03-26T02:41:12Z", "timestamp": 1711420872074 }, "is-referenced-by-count": 9, "issue": "3", "issued": { "date-parts": [ [ 2021, 3, 17 ] ] }, "journal-issue": { "issue": "3", "published-online": { "date-parts": [ [ 2021, 3, 17 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/publicdomain/zero/1.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 3, 17 ] ], "date-time": "2021-03-17T00:00:00Z", "timestamp": 1615939200000 } } ], "link": [ { "URL": "https://dx.plos.org/10.1371/journal.pone.0248128", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "340", "original-title": [], "page": "e0248128", "prefix": "10.1371", "published": { "date-parts": [ [ 2021, 3, 17 ] ] }, "published-online": { "date-parts": [ [ 2021, 3, 17 ] ] }, "publisher": "Public Library of Science (PLoS)", "reference": [ { "DOI": "10.1016/j.jcrc.2020.03.005", "article-title": "A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19", "author": "A Cortegiani", "doi-asserted-by": "crossref", "first-page": "279", "journal-title": "J Crit Care", "key": "pone.0248128.ref001", "volume": "57", "year": "2020" }, { "article-title": "Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis", "author": "T Fiolet", "journal-title": "Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis", "key": "pone.0248128.ref002", "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": "X Yao", "doi-asserted-by": "crossref", "first-page": "732", "issue": "15", "journal-title": "Clin Infect Dis an Off Publ Infect Dis Soc Am", "key": "pone.0248128.ref003", "volume": "71", "year": "2020" }, { "DOI": "10.1016/j.dsx.2020.05.017", "article-title": "Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis", "author": "AK Singh", "doi-asserted-by": "crossref", "first-page": "589", "issue": "4", "journal-title": "Diabetes Metab Syndr.", "key": "pone.0248128.ref004", "volume": "14", "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": "P Gautret", "doi-asserted-by": "crossref", "first-page": "105949", "issue": "1", "journal-title": "Int J Antimicrob Agents", "key": "pone.0248128.ref005", "volume": "56", "year": "2020" }, { "key": "pone.0248128.ref006", "unstructured": "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19—RECOVERY Trial [Internet]. 2020. Available from: 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-co" }, { "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": "ES Rosenberg", "doi-asserted-by": "crossref", "first-page": "2493", "issue": "24", "journal-title": "JAMA", "key": "pone.0248128.ref007", "volume": "323", "year": "2020" }, { "DOI": "10.1371/journal.pone.0237693", "article-title": "Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study", "author": "A Ip", "doi-asserted-by": "crossref", "first-page": "e0237693", "issue": "8", "journal-title": "PLoS One", "key": "pone.0248128.ref008", "volume": "15", "year": "2020" }, { "article-title": "Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19", "author": "AB Cavalcanti", "journal-title": "N Engl J Med", "key": "pone.0248128.ref009", "year": "2020" }, { "key": "pone.0248128.ref010", "unstructured": "Coronavirus Disease 2019 (COVID-19) Treatment Guidelines [Internet]. 2020. Available from: Coronavirus Disease 2019 (COVID-19)%0ATreatment Guidelines" }, { "DOI": "10.1126/science.abb5793", "article-title": "Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period", "author": "SM Kissler", "doi-asserted-by": "crossref", "first-page": "860", "issue": "6493", "journal-title": "Science", "key": "pone.0248128.ref011", "volume": "368", "year": "2020" }, { "article-title": "A Natural Language Processing System for National COVID-19 Surveillance in the US Department of Veterans Affairs", "author": "A Chapman", "key": "pone.0248128.ref012", "year": "2020" }, { "article-title": "Generalized Boosted Models: A guide to the gbm package", "author": "G Ridgeway", "first-page": "2007", "issue": "1", "journal-title": "Update", "key": "pone.0248128.ref013", "volume": "1" }, { "article-title": "gbm: Generalized boosted regression models", "author": "B Greenwell", "issue": "5", "journal-title": "R Packag version", "key": "pone.0248128.ref014", "volume": "2", "year": "2019" }, { "article-title": "WeightIt: Weighting for Covariate Balance in Observational Studies", "author": "N Greifer", "key": "pone.0248128.ref015", "year": "2020" } ], "reference-count": 15, "references-count": 15, "relation": {}, "resource": { "primary": { "URL": "https://dx.plos.org/10.1371/journal.pone.0248128" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Multidisciplinary" ], "subtitle": [], "title": "COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1371/journal.pone.corrections_policy", "volume": "16" }