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

Introduction Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to the anti-inflammatory effects and in vitro anti-viral activity and promising clinical benefits against influenza and other viruses. The aim of this study was to synthesize the best evidence on the efficacy and safety of nitazoxanide as treatment for patients with COVID-19. Methods Searches for studies were performed in peer-reviewed and gray literature. The following elements were used to define eligibility criteria: (1) Population, individuals with laboratory-confirmed SARS-CoV-2 infection; (2) Intervention, nitazoxanide; (3) Comparison, placebo; (4) Outcomes: positive RT-PCR status, composite measure of disease progression (severe COVID-19, ICU admission or invasive mechanical ventilation), death, serum biomarkers of inflammation (C-reactive protein, IL-6, and IL-8), and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCT). Treatment effects were reported as relative risk (RR) and mean difference (MD) with 95% confidence intervals (CI). Results Four blinded, placebo-controlled RCT were included in the meta-analysis and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in the frequency of positive RTP-PCR results (RR = 0.83; 95% CI 0.58 to 1.17) and there was no decreased risk for disease progression (severe COVID-19, ICU admission or invasive mechanical ventilation) (RR = 0.40; 95% CI 0.08 to 2.13) and deaths (RR = 0.55; 95% CI 0.18 to 1.68) among patients receiving nitazoxanide. There were no differences for patients treated with nitazoxanide and placebo in the levels of inflammatory markers. Conclusions In this study, we found no current evidence from blinded, placebo-controlled, RCT on the efficacy of nitazoxanide in treating patients with COVID-19. This living systematic review should be updated as soon as the results of ongoing RCT are published.