Early treatment with nitazoxanide prevents worsening of mild and moderate COVID-19 and subsequent hospitalization

Abstract

Background: There is an urgent need for treatments to prevent the progression to severe COVID-19 and hospitalization. Methods: This is a double-blind randomized multicenter study in 36 centers in the U.S. and Puerto Rico investigating the potential of a five-day treatment with nitazoxanide 300 mg extended release tablets in 379 outpatients with mild or moderate laboratory-confirmed COVID-19 with an onset of symptoms no more than 72 hours before inclusion. Key objectives were reduction of duration of symptoms (primary), progression to severe illness (key secondary), hospitalization and viral load. Results: Time to sustained response was not reduced by nitazoxanide (median: 13.28 and 12.35 days for nitazoxanide and placebo). Nitazoxanide treatment provided an 85% reduction in the progression to severe COVID-19 (1/184, [0.5%] nitazoxanide vs. 7/195, [3.6%] placebo). In subjects at high-risk according to CDC criteria, 1/112 (0.9%) of nitazoxanide-treated subjects and 7/126 (5.6%) of placebo-treated subjects experienced progression to severe COVID-19. Treatment led to a 79% reduction in the rate of hospitalization (1/184 [0.5%] nitazoxanide vs. 5/195 [2.6%] placebo). The proportions positive for SARS-CoV-2 RNA and viral load at days 4 and 10 were not reduced. Nitazoxanide was safe and well tolerated. Conclusions: Treatment of mild or moderate COVID-19 with a five-day course of oral nitazoxanide was safe and well tolerated and was associated with an 85% reduction in the progression to severe illness.