Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial

Rocco, Patricia R. M.; Silva, Pedro L.; Cruz, Fernanda F.; Junior, Marco Antonio C. M.; Tierno, Paulo F. G. M. M.; Moura, Marcos A.; De Oliveira, Luís Frederico G.; Lima, Cristiano C.; Dos Santos, Ezequiel A.; Junior, Walter F.; Fernandes, Ana Paula S. M.; Franchini, Kleber G.; Magri, Erick; de Moraes, Nara F.; Gonçalves, José Mário J.; Carbonieri, Melanie N.; Dos Santos, Ivonise S.; Paes, Natália F.; Maciel, Paula V. M.; Rocha, Raissa P.; de Carvalho, Alex F.; Alves, Pedro Augusto; Modena, José Luiz P.; Cordeiro, Artur T.; Trivella, Daniela B. B.; Marques, Rafael E.; Luiz, Ronir R.; Pelosi, Paolo; Lapa e Silva, Jose Roberto

Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on SARS-CoV-2 infection. In a multicenter, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of Covid-19 symptoms (dry cough, fever, and/or fatigue) were enrolled. After confirmation of SARS-CoV2 infection by RT-PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, TID, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation, and hospitalisation rate. Adverse events were also assessed. From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median time from symptom onset to first dose of study drug was 5 (4–5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was also reduced after nitazoxanide compared to placebo (p=0.006). The percent viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. In patients with mild Covid-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.