Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial
Patrícia R. M. Rocco, Pedro Leme Silva, Fernanda Ferreira Cruz, Marco Antonio C. Melo-Junior, Paulo F. G. M. M. Tierno, Marcos A. Moura, Luís Frederico G. De Oliveira, Cristiano C. Lima, Ezequiel Aparecido dos Santos, F. Walter, Ana Paula Fernandes, Kleber G. Franchini, Erick Magri, Nara Franzin de Moraes, José Mário J. Gonçalves, Melanie Nogueira Carbonieri, Ivonise S. Dos Santos, Natália F. Paes, Paula V. M. Maciel, Raíssa Prado Rocha, Alex F. Carvalho, Pedro Augusto Alves, José Luiz Proença‐Módena, Artur T. Cordeiro, Daniela Barretto Barbosa Trivella, Rafael Elias Marques, Ronir Raggio Luiz, Paolo Pelosi, José Roberto Lapa e Silva
Abstract
Background Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro . However, there is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods In a multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, three times daily, 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. Results From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median (interquartile range) 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 reduced after nitazoxanide compared to placebo (p=0.006). The percentage 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. Conclusions 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.