Nitazoxanide Therapy for Patients With COVID-19 Pneumonia

NCT04561219 | Completed Phase 2 DMC

• 3 other identifiers: SARITA-1RBR-88bs9x30662420.0.1001.0008
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms. Population: 500 Hospitalized patients with pneumonia derived from COVID-19 (Coronavirus Disease-19), either confirmed by RT-PCR (Real Time polymerase chain reaction), or suggested by typical findings on the computed tomography scan symptomatic. Experimental group: nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: placebo 8/8 hours for 5 days.

Conditions

Covid19; Corona Virus Infection; Pneumonia, Viral

Keywords

covid19; coronavirus; clinical trial; placebo-controlled; randomized; brazil; nitazoxanide; hospitalized patients; covid-19; sars-cov-2; new coronavirus; multicenter; double-blind

Outcome Measures

Primary Outcomes (1)

• Orotracheal intubation rate

  Compare the intubation rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by percentage.

  14 days

Secondary Outcomes (45)

• Hospitalisation days

  14 days

• ICU days

  14 days

• Intranasal oxygen support days

  14 days

• Mortality rate

  14 days

• Days with fever

  14 days

Other Outcomes (4)

• Adverse events - percentage

  Day 14

• Adverse events - absolute number

  Day 14

• Treatment discontinuation rate - absolute number

  Day 14

Study Arms (2)

Nitazoxanide

EXPERIMENTAL

Patients received nitazoxanide 500mg 8/8hours, for 5 days.

Drug: Nitazoxanide

Placebo

PLACEBO COMPARATOR

Patients received placebo 500mg 8/8hours, for 5 days

Drug: Placebo

Interventions

Nitazoxanide DRUG

Nitazoxanide 500mg three times a day for 5 days

Also known as: annita, azox, irose, tanisea, trinida, zoxany

Nitazoxanide

Placebo DRUG

Placebo three times a day for 5 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients requiring supplemental oxygen \[peripheral oxygen saturation (SpO2) \< 93%\], admitted to hospital with COVID-19 symptoms associated with chest computed tomography (CT) scan suggestive of viral pneumonia or positive nasopharyngeal swab test for SARS-CoV2 (RT-PCR)
• Age equal or superior to 18 years
• Non-pregnant women
• Willingness to receive study treatment
• Providing written and informed consent or the same consent signed by a family member

You may not qualify if:

• Impossibility to use oral medications
• History of severe liver disease (Child Pugh C class)
• Previous renal failure
• Severe heart failure (NYHA 3 or 4)
• COPD (GOLD 3 and 4)
• Neoplasia in the last 5 years
• Known autoimmune disease
• Individuals with known hypersensitivity to study drug
• Previous treatment with the study medication during the last 30 days
• Clinical suspicion of tuberculosis and bacterial pneumonia

Sponsors & Collaborators

• Universidade Federal do Rio de Janeiro: lead
• Ministry of Science and Technology, Brazil: collaborator
• National Research Council, Brazil: collaborator
• Financiadora de Estudos e Projetos: collaborator
• ATCGen: collaborator
• Hospital Central da Aeronáutica, Rio de Janeiro: collaborator
• Hospital da Força Aérea do Galeão: collaborator
• Hospital Naval Marcilio Dias: collaborator
• Hospital Universitario Pedro Ernesto: collaborator
• Hospital de Força Aérea de São Paulo: collaborator
• Hospital das Clínicas Luzia de Pinho Melo: collaborator
• Complexo Hospitalar Municipal de São Caetano do Sul: collaborator
• Hospital Municipal de Barueri Dr Francisco Moran: collaborator
• Hospital Regional de Sorocaba Dr Adib Domingos Jatene: collaborator
• Hospital Geral de São Mateus Dr Manoel Bifulco: collaborator
• Santa Casa de Misericórdia de Belo Horizonte: collaborator
• Mater Dei Hospital, Brazil: collaborator
• Hospital Eduardo de Menezes: collaborator
• Hospital das Clínicas da Universidade Federal de Pernambuco: collaborator
• Hospital das Forças Armadas, Brazil: collaborator
• Hospital Regional da Asa Norte, Brazil: collaborator
• Complexo Hospitalar do Trabalhador de Curitiba: collaborator
• Hospital Estadual de Doenças Tropicais Dr Anuar Auad: collaborator
• Hospital Geral de Fortaleza: collaborator

Study Sites (1)

Universidade Federal do Rio de Janeiro

Rio de Janeiro, 21941902, Brazil

Location

Related Publications (7)

• Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016 May-Jun;9(3):227-30. doi: 10.1016/j.jiph.2016.04.001. Epub 2016 Apr 16.

  PMID: 27095301 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

• Rajoli RK, Pertinez H, Arshad U, Box H, Tatham L, Curley P, Neary M, Sharp J, Liptrott NJ, Valentijn A, David C, Rannard SP, Aljayyoussi G, Pennington SH, Hill A, Boffito M, Ward SA, Khoo SH, Bray PG, O'Neill PM, Hong WD, Biagini G, Owen A. Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis. medRxiv [Preprint]. 2020 May 6:2020.05.01.20087130. doi: 10.1101/2020.05.01.20087130.

  PMID: 32511548 BACKGROUND

• Pepperrell T, Pilkington V, Owen A, Wang J, Hill AM. Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19. J Virus Erad. 2020 Apr 30;6(2):52-60. doi: 10.1016/S2055-6640(20)30017-0.

  PMID: 32405422 BACKGROUND

• Conceicao CCS, Martins CM, Medeiros Silva M, Neto HCCF, Chiumello D, Rocco PRM, Cruz FF, Silva PL. Predicting clinical outcomes at hospital admission of patients with COVID-19 pneumonia using artificial intelligence: a secondary analysis of a randomized clinical trial. Front Med (Lausanne). 2025 May 2;12:1561980. doi: 10.3389/fmed.2025.1561980. eCollection 2025.

  PMID: 40385586 DERIVED

• Silva PL, Cruz FF, Martins CM, Herrmann J, Gerard SE, Xin Y, Cereda M, Ball L, Pelosi P, Rocco PRM. A specific combination of laboratory data is associated with overweight lungs in patients with COVID-19 pneumonia at hospital admission: secondary cross-sectional analysis of a randomized clinical trial. Front Med (Lausanne). 2023 May 16;10:1137784. doi: 10.3389/fmed.2023.1137784. eCollection 2023.

  PMID: 37261117 DERIVED

• Rocco PRM, Silva PL, Cruz FF, Tierno PFGMM, Rabello E, Junior JC, Haag F, de Avila RE, da Silva JDG, Mamede MMS, Buchele KS, Barbosa LCV, Cabral AC, Junqueira AAF, Araujo-Filho JA, da Costa LATJ, Alvarenga PPM, Moura AS, Carajeleascow R, de Oliveira MC, Silva RGF, Soares CRP, Fernandes APSM, Fonseca FG, Camargos VN, Reis JS, Franchini KG, Luiz RR, Morais S, Sverdloff C, Martins CM, Felix NS, Mattos-Silva P, Nogueira CMB, Caldeira DAF, Pelosi P, Lapa-E-Silva JR. Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. Front Med (Lausanne). 2022 Apr 13;9:844728. doi: 10.3389/fmed.2022.844728. eCollection 2022.

  PMID: 35492335 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Pneumonia, Viral

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Pedro L Silva, PhD

  Universidade Federal do Rio de Janeiro

  STUDY CHAIR

• Patricia RM Rocco, MD, PhD

  Universidade Federal do Rio de Janeiro

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Patients were randomly allocated into one of the two groups: A or B. Patients received labelled medication: A or B, by the pharmacist. Patients received an identification number, so care providers, outcomes assessors and investigators did not know anything regarding the patients' groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Investigator

Model Details: Hospitalized patients with clinical signs of COVID-19, and either chest tomography scans suggestive of COVID-19 or confirmed by RT-PCR molecular tests, will be randomly divided into 2 groups: experimental and control groups. Experimental group: 250 hospitalized patients diagnosed with COVID-19 derived pneumonia will receive nitazoxanide 500mg 8/8 hs for 5 days. Control group: 250 hospitalized patients diagnosed with COVID-19 derived pneumonia will receive placebo 8/8 hs for 5 days.

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 23, 2020
• Study Start: April 19, 2020
• Primary Completion: October 2, 2020
• Study Completion: October 2, 2020
• Last Updated: July 22, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Available as soon as the editorial board of the journal accepting the manuscript requires.
• Access Criteria: Editorial board of the Journal accepting the manuscript.

Locations

BR (1)