Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: A systematic review and meta-analysis of blinded, placebo- controlled, randomized clinical trials

Purpose: Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study synthesized the best evidence on the efficacy and safety of nitazoxanide in COVID-19. Methods: : Searches for studies were performed in peer-reviewed and grey-literature. The following elements were used to define eligibility criteria: (1) Population, individuals with COVID-19; (2) Intervention, nitazoxanide; (3) Comparison, placebo; (4) Outcomes: viral load, positive RT-PCR status, composite measure of disease progression (ICU admission or invasive mechanical ventilation), death, serum biomarkers of inflammation, and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Results: : Five blinded, placebo-controlled RCTs were included and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in reducing viral load and frequency of positive RTP-PCR results. In addition, there was no decreased risk for disease progression and death among patients receiving nitazoxanide. Patients with COVID-19 treated with nitazoxanide had decreased levels of white blood cells, lactate dehydrogenase, and D-dimer compared to placebo, but the magnitude of effect was considered small to moderate. Conclusion: Available evidence based on the results of blinded, placebo-controlled, RCTs showed no clinical benefits of nitazoxanide in COVID-19.