Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection
Simiso Sokhela, Bronwyn Bosch, Andrew Hill, Bryony Simmons, Joana Woods, Hilary Johnstone, Godspower Akpomiemie, Leah Ellis, Andrew Owen, Carmen Perez Casas, Willem Daniel Francois Venter
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkac266
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.
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doi:10.1136/postgradmedj-2021-140287{ 'indexed': {'date-parts': [[2022, 8, 13]], 'date-time': '2022-08-13T04:28:59Z', 'timestamp': 1660364939996},
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'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\u2005weeks of either '
'nitazoxanide or sofosbuvir/daclatasvir as prevention, or standard prevention advice only. '
'Participants were evaluated every 4\u2005weeks for COVID-19 symptoms and had antibody and PCR '
'testing. The primary endpoint was positive SARS-CoV-2 PCR and/or serology ≥7\u2005days 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>',
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