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

Article scientifique 2022 Anglais

Résumé

Background 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. Methods 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). Results There was no difference in time to clinical improvement between the SoC ( n = 26) and SoC plus intervention arms ( n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492–1.638, p = 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, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251–1.140, p = 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 90 in 54% of patients. Tizoxanide was undetectable in saliva. Conclusion 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. Clinical trial registration [ https://clinicaltrials.gov/ct2/show/NCT04459286 ], identifier [NCT04459286].

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Fowotade, A., Bamidele, F., Egbetola, B., Fagbamigbe, A., Adeagbo, B., Adefuye, B., Olagunoye, A., Ojo, T., Adebiyi, A., Olagunju, O., Ladipo, O., Akinloye, A., Onayade, A., Bolaji, O., Rannard, S., Happi, C., Owen, A., Olagunju, A. (2022). A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19. https://doi.org/10.3389/fmed.2022.956123

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Auteur(s)

Adeola Fowotade Folasade Bamidele Boluwatife Egbetola Adeniyi Francis Fagbamigbe Babatunde Ayodeji Adeagbo Bolanle Adefuye Ajibola Olagunoye Temitope Olumuyiwa Ojo Akindele O. Adebiyi Omobolanle Ibitayo Olagunju Olabode Taiwo Ladipo Abdulafeez Akinloye Adedeji Onayade Oluseye O. Bolaji Steve P. Rannard Christian Happi Andrew Owen Adeniyi Olagunju

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