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, progression to severe illness, 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. The availability of a safe, oral, scalable, host-directed antiviral for the early treatment of COVID-19 could play an important role in reducing the number of severe illnesses and hospitalizations during this ongoing major public health crisis.Trial Registration Details: ClinicalTrials.gov Identifier: NCT04486313.Funding Information: This study was funded by the Romark Institute of Medical Research.Declaration of Interests: Jean-Francois Rossignol is an employee of and owns equity interest in Romark, L.C. Matthew Bardin, Jessica Fulgencio and Dena Mogelnicki are employees of Romark, L.C.; Christian Brechot is a senior adviser for Romark, L.C., an adviser for the Theravectys, Shanghai Vivo Biosciences and the chairman of The Healthy Aging company. Ethics Approval Statement: The central institutional review board (IRB) or a local IRB at each center approved the protocol.