A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19

Fowotade, Adeola, Bamidele, Folasade, Egbetola, Boluwatife, Fagbamigbe, Adeniyi F, Adeagbo, Babatunde A, Adefuye, Bolanle O, Olagunoye, Ajibola, Ojo, Temitope O, Adebiyi, Akindele O, Olagunju, Omobolanle I
et al (show 8 more authors) (2022) A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19. FRONTIERS IN MEDICINE, 9. 956123-.

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<h4>Background</h4>The nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19.<h4>Methods</h4>This is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286).<h4>Results</h4>There was no difference in time to clinical improvement between the SoC (<i>n</i> = 26) and SoC plus intervention arms (<i>n</i> = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492-1.638, <i>p</i> = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2-28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341-2.636, <i>p</i> = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251-1.140, <i>p</i> = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797-2,557), above its putative EC<sub>90</sub> in 54% of patients. Tizoxanide was undetectable in saliva.<h4>Conclusion</h4>Nitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial.<h4>Clinical trial registration</h4>[https://clinicaltrials.gov/ct2/show/NCT04459286], identifier [NCT04459286].

Item Type: Article
Uncontrolled Keywords: COVID-19, SARS-CoV-2, nitazoxanide (NTZ), atazanavir/ritonavir, pharmacokinetics
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: 09 Sep 2022 13:02
Last Modified: 18 Jan 2023 20:45
DOI: 10.3389/fmed.2022.956123
Open Access URL: https://www.frontiersin.org/articles/10.3389/fmed....
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3164014