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

Abstract

Background The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates’ drugs. Nitazoxanide (NTZ) has a broad antiviral effect. Methods This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg 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 20 th , 2020, to September 21 st , 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. Findings Two patients died in the NTZ arm compared to 6 in the placebo arm ( p = 0.564). NTZ was superior to placebo when considering SSD ( p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 ( p = 0.035), whereas the placebo group presented more adverse events ( p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo ( p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group ( p = 0.04). A decrease from baseline was higher in the NTZ group for d -Dimer ( p = 0.001), US-RCP ( p < 0.002), TNF ( p < 0.038), IL-6 ( p < 0.001), IL-8 ( p = 0.014), HLA DR. on CD4 + T lymphocytes ( p < 0.05), CD38 in CD4 + and CD8 + T (both p < 0.05), and CD38 and HLA-DR. on CD4+ ( p < 0.01) Interpretation 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.

A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19

“…In a multicenter, randomized, double-blind, placebo-controlled trial in patients hospitalized with moderate-to-severe COVID-19, treatment with nitazoxanide 600 mg twice daily for seven days was associated with reductions in rates of mortality and mechanical ventilation, duration of supplemental oxygen and time to hospital discharge compared to placebo. 20 …”

Drug Repurposing Against SARS-CoV-1, SARS-CoV-2 and MERS-CoV

“…A single 500 mg dose treatment of nitazoxanide reaches within 1–4 h to tizoxanide (active metabolite of nitazoxanide) plasma concentrations greater than 10 μM, with a half-life of 1.3–1.8 h and good tolerance [ 141 ]. Nitazoxanide 600 mg BID for 7 days has been evaluated in a randomized, double-blind pilot clinical trial versus Placebo among 50 hospitalized patients (25 in each arm) with mild respiratory insufficiency due to SARS-COV-2 infection ( ClinicalTrials.gov NCT04348409) [ 142 ]. Nitazoxanide showed superiority for the mean time of hospital discharge arm (6.6 vs 14 days, p = 0.021) and of negativation of the RT-PCR.…”

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview

“…(b) From 20 May to 21 September 2020, a randomized clinical trial comparing NTZ (600 mg, twice) against placebo for seven days in 50 COVID-19 patients with mild respiratory insufficiency. Interestingly, a decrease in the time for hospital discharge, faster clinical swab negativity, and a significant reduction in the levels of inflammatory and lymphocyte T cells activation markers were documented among NTZ-treated patients compared to placebo [162].…”