Nitazoxanide superiority to placebo to treat moderate COVID-19 – A Pilot prove of concept randomized double-blind clinical trial.

Abstract

\n Background\n The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates’ drugs. Nitazoxanide (NTZ) has a broad antiviral effect.\n \n Methods\n This was a randomized, double-blind pilot clinical trial comparing NTZ 600\xa0mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used.\n \n Findings\n Two patients died in the NTZ arm compared to 6 in the placebo arm (p\xa0=\xa00.564). NTZ was superior to placebo when considering SSD (p\xa0<\xa00001), the mean time for hospital discharge (6.6\xa0vs. 14 days, p\xa0=\xa00.021), and negative PCR at day 21 (p\xa0=\xa00.035), whereas the placebo group presented more adverse events (p\xa0=\xa00.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p\xa0=\xa00.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p\xa0=\xa00.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p\xa0=\xa00.001), US-RCP (p\xa0<\xa00.002), TNF (p\xa0<\xa00.038), IL-6 (p\xa0<\xa00.001), IL-8 (p\xa0=\xa00.014), HLA DR. on CD4+ \n T lymphocytes (p\xa0<\xa00.05), CD38 in CD4+ and CD8+ \n T (both p\xa0<\xa00.05), and CD38 and HLA-DR. on CD4+ (p\xa0<\xa00.01)\n \n Interpretation\n Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.\n