Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoV-2 Virus Infection (COVID-19)

NCT04463264 | Unknown Phase 2 DMC

• 1 other identifier: NTZ-COVID ARG1
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation of the efficacy and safety of NTX in adult patients (≥18 years and \<60 years), with SARS-CoV-2 infection with mild symptoms of COVID-19, compared to a placebo control arm. 135 patients will be randomized to either Nitazoxanide (n=90) or placebo (n=45) (2:1). Simple blind design. Primary endpoint: eradication of virus from patients' respiratory tract secretions by the 7th day of treatment.

Conditions

COVID-19

Keywords

Nitazoxanide; Coronavirus Infections; RNA Virus Infections; Respiratory Tract Infections; Virus Diseases; Respiratory Tract Diseases; Antiparasitic Agents

Outcome Measures

Primary Outcomes (1)

• Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th.

  Erradication will be considered a reduction of the viral load on day 7 greater than 35% with respect to placebo. Extraction of genomic material will be performed using a QIAgen mini kit (QIAmp viral RNA) validated by the CDC (United States Center for Disease Control and Prevention (https://www.fda.gov/media/134922/download) (CDC-006-00019) Viral load will be quantified with the following detection kits: Commercial Kit: PCR-EUA-CDC-nCoV-IFU. Commercial KIT SENTINEL - STAT-NAT Covid 19B (Berlín). Rational: In mild cases of COVID-19, 50% of the patients eradicated the virus within a period of 3 weeks, 25% eradicated the virus before the 13th day, 75% during the first month and the rest were " late eradicators." This latter subgroup of patients has been associated with severe cases of COVID-19 disease.

  7 day

Secondary Outcomes (4)

• Comparative decrease of the viral load

  3 - 35 days

• Clinical improvement

  1 - 35 days

• Pneumonia patients meeting severity criteria.

  1 - 35 days

• Number of days with fever

  1 - 35 days

Other Outcomes (7)

• Patients requiring mechanical ventilation

  1 - 35 days

• Mortality rate.

  1- 35 days

• Lymphocyte recovery

  7 day

Study Arms (2)

NTX active treatment

EXPERIMENTAL

Intervention: NTX (500 mg every 6 hours for 14 days) orally with food (P.O.).

Drug: Nitazoxanide

Intervention: placebo

PLACEBO COMPARATOR

Placebo (1 tablet every 6 hours for 14 days) orally with food (P.O.).

Drug: Placebo

Interventions

Nitazoxanide DRUG

NTX (500 mg every 6 hours for 14 days) orally with food (P.O.).

NTX active treatment

Placebo DRUG

Placebo (1 tablet every 6 hours for 14 days) orally with food (P.O.).

Intervention: placebo

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult male and female patients (≥ 18 years and \<60 years).
• Signature of informed consent.
• Patients with a positive test for SARS-CoV-2 and mild symptoms of COVID-19 (without severity criteria as detailed by the Ministry of Health of Argentina - MSN)

You may not qualify if:

• Patients under 18 years of age and over 60 years of age.
• Breastfeeding or pregnant women (with positive pregnancy blood test in women of childbearing age).
• Patients with mild pneumonia in the presence of risk factors or moderate or severe pneumonia (based on the severity criteria set by the Ministry of Health of Argentina), or patients who require mechanical ventilation at screening.
• Patients in whom NTX and/or lactose is contraindicated.
• Any other contraindication based on the judgment of the treating physician.

Sponsors & Collaborators

• Laboratorios Roemmers S.A.I.C.F.: lead

Study Sites (1)

Hospital Universitario Austral

Presidente Derqui, Buenos Aires, Argentina, 1629, Argentina

RECRUITING

Related Publications (9)

• Ashiru O, Howe JD, Butters TD. Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. Virology. 2014 Aug;462-463:135-48. doi: 10.1016/j.virol.2014.05.015. Epub 2014 Jun 25.

  PMID: 24971706 BACKGROUND

• Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554776/

  PMID: 32150360 BACKGROUND

• Chen J, Lau YF, Lamirande EW, Paddock CD, Bartlett JH, Zaki SR, Subbarao K. 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. 2010 Feb;84(3):1289-301. doi: 10.1128/JVI.01281-09. Epub 2009 Nov 11.

  PMID: 19906920 BACKGROUND

• Chang D, Mo G, Yuan X, Tao Y, Peng X, Wang FS, Xie L, Sharma L, Dela Cruz CS, Qin E. Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection. Am J Respir Crit Care Med. 2020 May 1;201(9):1150-1152. doi: 10.1164/rccm.202003-0524LE. No abstract available.

  PMID: 32200654 BACKGROUND

• Frieman M, Baric R. Mechanisms of severe acute respiratory syndrome pathogenesis and innate immunomodulation. Microbiol Mol Biol Rev. 2008 Dec;72(4):672-85, Table of Contents. doi: 10.1128/MMBR.00015-08.

  PMID: 19052324 BACKGROUND

• Haffizulla J, Hartman A, Hoppers M, Resnick H, Samudrala S, Ginocchio C, Bardin M, Rossignol JF; US Nitazoxanide Influenza Clinical Study Group. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. 2014 Jul;14(7):609-18. doi: 10.1016/S1473-3099(14)70717-0. Epub 2014 May 19.

  PMID: 24852376 BACKGROUND

• Jasenosky LD, Cadena C, Mire CE, Borisevich V, Haridas V, Ranjbar S, Nambu A, Bavari S, Soloveva V, Sadukhan S, Cassell GH, Geisbert TW, Hur S, Goldfeld AE. The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus. iScience. 2019 Sep 27;19:1279-1290. doi: 10.1016/j.isci.2019.07.003. Epub 2019 Aug 8.

  PMID: 31402258 BACKGROUND

• Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014 Oct;110:94-103. doi: 10.1016/j.antiviral.2014.07.014. Epub 2014 Aug 7.

  PMID: 25108173 BACKGROUND

• Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. No abstract available.

  PMID: 32020029 BACKGROUND

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; RNA Virus Infections; Respiratory Tract Infections; Virus Diseases; Respiratory Tract Diseases

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Infections; Coronaviridae Infections; Nidovirales Infections; Lung Diseases

Study Officials

• Marcelo Silva, MD

  Austral University, Argentina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcelo Silva, MD

CONTACT

(+54 11) 6418-1701; MSILVA@cas.austral.edu.ar

Diego Enriquez, MD

CONTACT

(+54 11) 6432-3240; denriquez@roemmers.com.ar

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Simple blind design
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized. Nitazoxanide : Placebo (2:1), parallel-group study

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: July 9, 2020
• Study Start: June 26, 2020
• Primary Completion: November 15, 2020
• Study Completion: December 26, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)