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

Sokhela, Simiso, Bosch, Bronwyn, Hill, Andrew, Simmons, Bryony, Woods, Joana, Johnstone, Hilary, Akpomiemie, Godspower, Ellis, Leah, Owen, Andrew, Casas, Carmen Perez and Venter, Willem Daniel Francois (2022) Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection. The Journal of Antimicrobial Chemotherapy, 77 (10). 2706 - 2712. ISSN 0305-7453

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Item Type:	Article
Official URL:	https://academic.oup.com/jac
Additional Information:	© 2022 The Authors
Divisions:	LSE Health
Subjects:	R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine H Social Sciences > HV Social pathology. Social and public welfare. Criminology R Medicine > RM Therapeutics. Pharmacology
Date Deposited:	24 Oct 2022 13:18
Last Modified:	20 Sep 2025 02:17
URI:	http://eprintstest.lse.ac.uk/id/eprint/117167

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