AUTHOR=Rocco Patricia R. M. , Silva Pedro L. , Cruz Fernanda F. , Tierno Paulo F. G. M. M. , Rabello Eucir , Junior Jéfiton Cordeiro , Haag Firmino , de Ávila Renata E. , da Silva Joana D. G. , Mamede Mariana M. S. , Buchele Konrad S. , Barbosa Luiz C. V. , Cabral Anna C. , Junqueira Antônio A. F. , Araújo-Filho João A. , da Costa Lucianna A. T. J. , Alvarenga Pedro P. M. , Moura Alexandre S. , Carajeleascow Ricardo , de Oliveira Mirella C. , Silva Roberta G. F. , Soares Cynthia R. P. , Fernandes Ana Paula S. M. , Fonseca Flavio Guimarães , Camargos Vidyleison Neves , Reis Julia de Souza , Franchini Kleber G. , Luiz Ronir R. , Morais Sirlei , Sverdloff Carlos , Martins Camila Marinelli , Felix Nathane S. , Mattos-Silva Paula , Nogueira Caroline M. B. , Caldeira Dayene A. F. , Pelosi Paolo , Lapa-e-Silva José R. TITLE=Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.844728 DOI=10.3389/fmed.2022.844728 ISSN=2296-858X ABSTRACT=Background

Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.

Methods

A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days.

Results

Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38–1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21–3.43], p < 0.0001), time to hospital discharge (1.37 [1.11–1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64–0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed.

Conclusions

Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.

Clinical Trial Registration

Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.