Efficacy of Nitazoxanide in reducing the viral ad in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel-group, pilot study.

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8-Apr-3364.pdf
Published Feb 28, 2023
DOI: https://doi.org/10.18103/mra.v11i2.3364

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Marcelo Silva
Hospital Universitario Austral, Pilar, Argentina.
Andrés Espejo
Hospital Universitario Austral, Pilar, Argentina.
María L Pereyra
Hospital Universitario Austral, Pilar, Argentina.
Martín Lynch
Hospital Universitario Austral, Pilar, Argentina.
Marcos Thompson
Hospital Universitario Austral, Pilar, Argentina.
Luciana Laborde
Hospital Universitario Austral, Pilar, Argentina.
Hernán Taconelli
Sanatorio Nuestra Señora del Pilar, Ciudadela, Argentina.
Patricia Patricia
IIHEMA, IMEX-CONICET, Academia Nacional de Medicina.
Matías J Pereson
IIHEMA, IMEX-CONICET, Academia Nacional de Medicina.
Marcelo Garbini
Departamento de Investigación Clínica, Laboratorios Roemmers.
Pablo Crucci
Departamento de Investigación Clínica, Laboratorios Roemmers.
Diego Enriquez
Departamento de Investigación Clínica, Laboratorios Roemmers.

Abstract

The fast spread of COVID-19 has overcrowded Public Health Systems facilities in major countries due to the large number of seriously ill patients, particularly those requiring admission to intensive care units. Reducing viral load, along with other recommended epidemiological measures, such as social distancing and home confinement, can in time significantly help to reduce the infection R0 (Basic Reproductive Rate) and then mitigate disease burden.


Early negativization or otherwise reduction of the viral load can potentially diminish disease severity, resulting in a better-controlled public health response, avoiding collapse of healthcare systems. Nitazoxanide, a widely used thiazolide approved by the FDA as an antiparasitic drug, also approved in Brazil for Norovirus and Rotavirus treatments, has an excellent safety record for a variety of indications. Nitazoxanide exhibits activity in vitro against MERS-CoV and other coronaviruses; and a specific antiviral effect (in micro molar doses) against SARS-CoV-2.


The objective of this study was to evaluate the efficacy and safety of Nitazoxanide in reducing the SARS-COV 2 viral load within 7 days of treatment in respiratory samples from COVID-19-infected patients with mild to moderate disease, compared to placebo.


An interim analysis showed that the ratio of patients with a viral load reduction ≥ 35% from baseline up to day 7 of treatment was significantly greater for Nitazoxanide compared to placebo (47.8% vs. 15.4%; Δ 34.6%; 95% CI: 64.7; 4.6: p = 0.037).

Keywords: Nitazoxanide, COVID-19, viral load,, antiviral, SARS-Cov-2

Article Details

How to Cite
SILVA, Marcelo et al. Efficacy of Nitazoxanide in reducing the viral ad in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel-group, pilot study.. Medical Research Archives, [S.l.], v. 11, n. 2, feb. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3364>. Date accessed: 03 dec. 2023. doi: https://doi.org/10.18103/mra.v11i2.3364.
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Issue
Vol 11 No 2 (2023): February Issue, Vol.11 Issue 2
Section
Case Reports

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References

1. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30 (3):269– 271. doi:10.1038/s41422-020- 0282-0.
2. Cascella, M., Rajnik M, Cuomo A, et al. Features, Evaluation and Treatment Coronavirus (COVID- 19) [Updated 2020 Oct4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearlsPublishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/
3. Beigel JH, Tomashek KM, Dodd LE, et al; ACTT-1 Study Group Members. Remdesivir for the treatment of COVID-19: final report. N Engl J Med 2020;383:1813-26. DOI: 10.1056/NEJMoa2007764. Published online October 8 and updated on October 9, 2020, at NEJM.org, 2020.
4. Abella BS, Jolkovsky EL, Biney BT, et al. Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial. JAMA Intern Med. 2021;181(2):195–202. doi:10.1001/jamainternmed.2020.6319.
5. Kim PS, Read SW, Fauci AS. Therapy for Early COVID-19: A Critical Need. JAMA. 2020;324(21):2149–2150. doi:10.1001/jama.2020.22813.
6. Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014;110:94–103. doi:10.1016/j.antiviral.2014.07.014.
7. Hui DS, Lee N, Chan PK, Beigel JH. The role of adjuvant immunomodulatory agents for treatment of severe influenza. Antiviral Res. 2018;150:202‐216. doi:10.1016/j.antiviral. 2018.01.002.
8. Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016;9(3):227–230. doi:10.1016/j.jiph.2016.04.001.
9. Ashiru O, Howe JD, Butters TD. Nitazoxanide, an antiviral thiazolide, depletes ATP- sensitive intracelular Ca (2+) stores. Virology. 2014;462-463:135‐148. doi:10.1016/j.virol. 2014.05.015
10. Jasenosky LD, Cadena C, Mire CE, et al. The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus. iScience. 2019; 19:1279–1290. doi:10.1016/j.isci.2019.07.003.
11. Hong S, Kim HJ, Song CS et al Nitazoxanide suppresses IL-6 production in LPS-stimulated mouse macrophages and TG-injected mice. International Immunopharmacology, Volume 13, Issue 1,2012,Pages 23-27,ISSN 1567-5769, https://doi.org/10.1016/j.intimp.2012.03.002.
12. Chen J, Lau YF, Lamirande EW, et al. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. J Virol.Jan 2010;84(3):1289–1301. doi:10.1128/JVI.01281-0915.
13. Balderas-Acata J, Bueno E, Pérez-Becerril F, et al. (2011). Bioavailability of Two Oral-Suspension Formulations of a Single Dose of Nitazoxanide 500 mg: An Open-Label, Randomized-Sequence, Two-Period Crossover, Comparison in Healthy Fasted Mexican Adult Volunteers. Journal of Bioequivalence & Bioavailability. 03. 10.4172/jbb.1000056.
14. Rajoli, RKR, Pertinez, H, Arshad, U, et al. Dose prediction for repurposing nitazoxanide in SARS‐ CoV‐2 treatment or chemoprophylaxis. Br J Clin Pharmacol. 2021;1– 11. https://doi.org/10.1111/bcp.14619
15. Haffizulla J, Hartman A, Hoppers M, et al. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo controlled, phase 2b/3trial. Lancet Infect Dis. 2014;14(7):609–618. doi:10.1016/S1473-3099(14)70717-0.
16. Rocco PRM, Silva PL, Cruz FF, et al. Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial. Eur Respir J 2020; in press (https://doi.org/10.1183/13993003.03725-2020
17. ClinicalTrails.gov.https://clinicaltrials.gov/ct2/results?cond=COVID&term=Nitazoxanide&cntry= &state=&city=&dist=.
18. Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS- CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020 Apr 21;369:m1443. doi: 10.1136/bmj.m1443. PMID: 32317267; PMCID: PMC7190077.
19. De Chang D, Mo G, Yuan X, et al. Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection. Am J Respir Crit CareMed. 2020;201(9):1150‐1152. doi:10.1164/rccm.202003-0524LE.
20. Chen P, Nirula A, Heller b. et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med 2021;384:229-37. DOI: 10.1056/NEJMoa2029849.
21. Pujadas E, Chaudhry F, McBride R, et al. SARS-CoV-2 viral load predicts COVID-19 mortality. The Lancet Respiratory Medicine, Volume 8, Issue 9, e70.
22. Riediker M, Tsai D. Estimation of Viral Aerosol Emissions From Simulated Individuals With Asymptomatic to Moderate Coronavirus Disease 2019. JAMA Netw Open. 2020;3(7):e2013807. doi:10.1001/jamanetworkopen.2020.13807
23. Rocco P, Silva P, CruF, et al. Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. Front. Med. 9:844728. 2022. doi: 10.3389/fmed.2022.844728