Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection

DOI record: { "DOI": "10.1093/jac/dkac266", "ISSN": [ "0305-7453", "1460-2091" ], "URL": "http://dx.doi.org/10.1093/jac/dkac266", "abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>The COVER trial evaluated whether nitazoxanide or sofosbuvir/daclatasvir could lower the risk of SARS-CoV-2 infection. Nitazoxanide was selected given its favourable pharmacokinetics and in vitro antiviral effects against SARS-CoV-2. Sofosbuvir/daclatasvir had shown favourable results in early clinical trials.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>In this clinical trial in Johannesburg, South Africa, healthcare workers and others at high risk of infection were randomized to 24 weeks of either nitazoxanide or sofosbuvir/daclatasvir as prevention, or standard prevention advice only. Participants were evaluated every 4 weeks for COVID-19 symptoms and had antibody and PCR testing. The primary endpoint was positive SARS-CoV-2 PCR and/or serology ≥7 days after randomization, regardless of symptoms. A Poisson regression model was used to estimate the incidence rate ratios of confirmed SARS-CoV-2 between each experimental arm and control.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Between December 2020 and January 2022, 828 participants were enrolled. COVID-19 infections were confirmed in 100 participants on nitazoxanide (2234 per 1000 person-years; 95% CI 1837–2718), 87 on sofosbuvir/daclatasvir (2125 per 1000 person-years; 95% CI 1722–2622) and 111 in the control arm (1849 per 1000 person-years; 95% CI 1535–2227). There were no significant differences in the primary endpoint between the treatment arms, and the results met the criteria for futility. In the safety analysis, the frequency of grade 3 or 4 adverse events was low and similar across arms.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>In this randomized trial, nitazoxanide and sofosbuvir/daclatasvir had no significant preventative effect on infection with SARS-CoV-2 among healthcare workers and others at high risk of infection.</jats:p>\n </jats:sec>", "author": [ { "ORCID": "http://orcid.org/0000-0002-2707-1533", "affiliation": [ { "name": "Ezintsha, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg , South Africa" } ], "authenticated-orcid": false, "family": "Sokhela", "given": "Simiso", "sequence": "first" }, { "affiliation": [ { "name": "Ezintsha, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg , South Africa" } ], "family": "Bosch", "given": "Bronwyn", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pharmacology and Therapeutics, University of Liverpool , Liverpool , UK" } ], "family": "Hill", "given": "Andrew", "sequence": "additional" }, { "affiliation": [ { "name": "LSE Health, London School of Economics & Political Science , London , UK" } ], "family": "Simmons", "given": "Bryony", "sequence": "additional" }, { "affiliation": [ { "name": "Ezintsha, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg , South Africa" } ], "family": "Woods", "given": "Joana", "sequence": "additional" }, { "affiliation": [ { "name": "HJ-Clinical Trial Consultancy , George , South Africa" } ], "family": "Johnstone", "given": "Hilary", "sequence": "additional" }, { "affiliation": [ { "name": "Ezintsha, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg , South Africa" } ], "family": "Akpomiemie", "given": "Godspower", "sequence": "additional" }, { "affiliation": [ { "name": "Imperial College London, School of Public Health , London , UK" } ], "family": "Ellis", "given": "Leah", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-9819-7651", "affiliation": [ { "name": "Department of Pharmacology and Therapeutics, University of Liverpool , Liverpool , UK" } ], "authenticated-orcid": false, "family": "Owen", "given": "Andrew", "sequence": "additional" }, { "affiliation": [ { "name": "Unitaid, Global Health Campus , Chem. du Pommier 40, 1218 Le Grand-Saconnex , Switzerland" } ], "family": "Casas", "given": "Carmen Perez", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4157-732X", "affiliation": [ { "name": "Ezintsha, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg , South Africa" } ], "authenticated-orcid": false, "family": "Venter", "given": "Willem Daniel Francois", "sequence": "additional" } ], "container-title": "Journal of Antimicrobial Chemotherapy", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2022, 8, 12 ] ], "date-time": "2022-08-12T03:49:08Z", "timestamp": 1660276148000 }, "deposited": { "date-parts": [ [ 2022, 8, 12 ] ], "date-time": "2022-08-12T03:49:38Z", "timestamp": 1660276178000 }, "funder": [ { "award": [ "2016-07-Wits" ], "name": "RHI" } ], "indexed": { "date-parts": [ [ 2022, 8, 13 ] ], "date-time": "2022-08-13T04:28:59Z", "timestamp": 1660364939996 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2022, 8, 12 ] ] }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by-nc/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 8, 12 ] ], "date-time": "2022-08-12T00:00:00Z", "timestamp": 1660262400000 } } ], "link": [ { "URL": "https://academic.oup.com/jac/advance-article-pdf/doi/10.1093/jac/dkac266/45349402/dkac266.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "syndication" }, { "URL": "https://academic.oup.com/jac/advance-article-pdf/doi/10.1093/jac/dkac266/45349402/dkac266.pdf", "content-type": "unspecified", 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