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 ORCID: 0000-0002-9819-7651, Casas, Carmen Perez
et al (show 1 more authors) (2022) Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 77 (10). pp. 2706-2712.

[thumbnail of Randomized clinical trial of nitazoxanide or sofosbuvirdaclatasvir for the prevention of SARS-CoV-2 infection.pdf] PDF
Randomized clinical trial of nitazoxanide or sofosbuvirdaclatasvir for the prevention of SARS-CoV-2 infection.pdf - Published version

Download (229kB) | Preview

Abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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
Uncontrolled Keywords: Humans, Carbamates, Nitro Compounds, Imidazoles, Pyrrolidines, Thiazoles, Valine, Antiviral Agents, Treatment Outcome, South Africa, Sofosbuvir, COVID-19, SARS-CoV-2
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 28 Oct 2022 15:04
Last Modified: 18 Jan 2023 19:48
DOI: 10.1093/jac/dkac266
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165852