Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial
BackgroundNitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.MethodsA multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospital...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-04-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.844728/full |
| _version_ | 1818050532359536640 |
|---|---|
| author | Patricia R. M. Rocco Pedro L. Silva Fernanda F. Cruz Paulo F. G. M. M. Tierno Eucir Rabello Jéfiton Cordeiro Junior Firmino Haag Renata E. de Ávila Joana D. G. da Silva Mariana M. S. Mamede Konrad S. Buchele Luiz C. V. Barbosa Anna C. Cabral Antônio A. F. Junqueira João A. Araújo-Filho Lucianna A. T. J. da Costa Pedro P. M. Alvarenga Alexandre S. Moura Ricardo Carajeleascow Mirella C. de Oliveira Roberta G. F. Silva Cynthia R. P. Soares Ana Paula S. M. Fernandes Flavio Guimarães Fonseca Vidyleison Neves Camargos Julia de Souza Reis Kleber G. Franchini Ronir R. Luiz Sirlei Morais Carlos Sverdloff Camila Marinelli Martins Nathane S. Felix Paula Mattos-Silva Caroline M. B. Nogueira Dayene A. F. Caldeira Paolo Pelosi Paolo Pelosi José R. Lapa-e-Silva |
| author_facet | Patricia R. M. Rocco Pedro L. Silva Fernanda F. Cruz Paulo F. G. M. M. Tierno Eucir Rabello Jéfiton Cordeiro Junior Firmino Haag Renata E. de Ávila Joana D. G. da Silva Mariana M. S. Mamede Konrad S. Buchele Luiz C. V. Barbosa Anna C. Cabral Antônio A. F. Junqueira João A. Araújo-Filho Lucianna A. T. J. da Costa Pedro P. M. Alvarenga Alexandre S. Moura Ricardo Carajeleascow Mirella C. de Oliveira Roberta G. F. Silva Cynthia R. P. Soares Ana Paula S. M. Fernandes Flavio Guimarães Fonseca Vidyleison Neves Camargos Julia de Souza Reis Kleber G. Franchini Ronir R. Luiz Sirlei Morais Carlos Sverdloff Camila Marinelli Martins Nathane S. Felix Paula Mattos-Silva Caroline M. B. Nogueira Dayene A. F. Caldeira Paolo Pelosi Paolo Pelosi José R. Lapa-e-Silva |
| author_sort | Patricia R. M. Rocco |
| collection | DOAJ |
| description | BackgroundNitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.MethodsA 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.ResultsOf 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.ConclusionsNitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.Clinical Trial RegistrationBrazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219. |
| first_indexed | 2024-12-10T10:54:58Z |
| format | Article |
| id | doaj.art-9d9290159d524fa783e9416ee099101a |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-10T10:54:58Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-9d9290159d524fa783e9416ee099101a2022-12-22T01:51:55ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-04-01910.3389/fmed.2022.844728844728Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled TrialPatricia R. M. Rocco0Pedro L. Silva1Fernanda F. Cruz2Paulo F. G. M. M. Tierno3Eucir Rabello4Jéfiton Cordeiro Junior5Firmino Haag6Renata E. de Ávila7Joana D. G. da Silva8Mariana M. S. Mamede9Konrad S. Buchele10Luiz C. V. Barbosa11Anna C. Cabral12Antônio A. F. Junqueira13João A. Araújo-Filho14Lucianna A. T. J. da Costa15Pedro P. M. Alvarenga16Alexandre S. Moura17Ricardo Carajeleascow18Mirella C. de Oliveira19Roberta G. F. Silva20Cynthia R. P. Soares21Ana Paula S. M. Fernandes22Flavio Guimarães Fonseca23Vidyleison Neves Camargos24Julia de Souza Reis25Kleber G. Franchini26Ronir R. Luiz27Sirlei Morais28Carlos Sverdloff29Camila Marinelli Martins30Nathane S. Felix31Paula Mattos-Silva32Caroline M. B. Nogueira33Dayene A. F. Caldeira34Paolo Pelosi35Paolo Pelosi36José R. Lapa-e-Silva37Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilHospital Municipal de Barueri Dr. Francisco Moran, Barueri, BrazilHospital da Força Aérea do Galeão, Rio de Janeiro, BrazilHospital Regional de Sorocaba Dr. Adib D Jatene- Bata Branca, São Paulo, BrazilHospital Geral de São Mateus – Dr. Manoel Bifulco, São Mateus, BrazilHospital Eduardo Menezes, Belo Horizonte, BrazilHospital Regional da Asa Norte, Brasília, BrazilHospital das Forças Armadas, Brasília, BrazilHospital Naval Marcilio Dias, Rio de Janeiro, Brazil0Hospital das Clínicas Luzia de Pinho Melo, Mogi das Cruzes, Brazil1Hospital Universitário Pedro Ernesto, Rio de Janeiro, Brazil2Hospital Central da Aeronáutica, Rio de Janeiro, Brazil3Hospital Estadual de Doenças Tropicais Dr. Anuar Auad, Anápolis, Brazil4Hospital Geral de Fortaleza, Fortaleza, Brazil5Hospital Mater Dei, Belo Horizonte, Brazil6Santa Casa de Misericórdia de Belo Horizonte, Belo Horizonte, Brazil7Complexo Hospitalar Municipal de São Caetano do Sul, Sao Caetano do Sul, Brazil8Complexo do Trabalhador de Curitiba, Curitiba, Brazil9Hospital da Força Aérea de São Paulo, São Paulo, Brazil0Hospital das Clínicas da Universidade Federal do Pernambuco, Recife, Brazil1Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil1Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil1Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil1Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil2Brazilian Centre for Research in Energy and Materials, Campinas, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil3ATCGEN, Campinas, Brazil3ATCGEN, Campinas, Brazil4AAC&T Research Consulting LTDA, Curitiba, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil5Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy6Anesthesia and Critical Care, San Martino Policlinico Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) for Oncology and Neurosciences, Genoa, ItalyCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilBackgroundNitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.MethodsA 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.ResultsOf 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.ConclusionsNitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.Clinical Trial RegistrationBrazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.https://www.frontiersin.org/articles/10.3389/fmed.2022.844728/fullD-dimeroxygenationpneumoniaSARS-CoV-2COVID-19 |
| spellingShingle | Patricia R. M. Rocco Pedro L. Silva Fernanda F. Cruz Paulo F. G. M. M. Tierno Eucir Rabello Jéfiton Cordeiro Junior Firmino Haag Renata E. de Ávila Joana D. G. da Silva Mariana M. S. Mamede Konrad S. Buchele Luiz C. V. Barbosa Anna C. Cabral Antônio A. F. Junqueira João A. Araújo-Filho Lucianna A. T. J. da Costa Pedro P. M. Alvarenga Alexandre S. Moura Ricardo Carajeleascow Mirella C. de Oliveira Roberta G. F. Silva Cynthia R. P. Soares Ana Paula S. M. Fernandes Flavio Guimarães Fonseca Vidyleison Neves Camargos Julia de Souza Reis Kleber G. Franchini Ronir R. Luiz Sirlei Morais Carlos Sverdloff Camila Marinelli Martins Nathane S. Felix Paula Mattos-Silva Caroline M. B. Nogueira Dayene A. F. Caldeira Paolo Pelosi Paolo Pelosi José R. Lapa-e-Silva Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial Frontiers in Medicine D-dimer oxygenation pneumonia SARS-CoV-2 COVID-19 |
| title | Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial |
| title_full | Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial |
| title_fullStr | Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial |
| title_full_unstemmed | Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial |
| title_short | Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial |
| title_sort | nitazoxanide in patients hospitalized with covid 19 pneumonia a multicentre randomized double blind placebo controlled trial |
| topic | D-dimer oxygenation pneumonia SARS-CoV-2 COVID-19 |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.844728/full |
| work_keys_str_mv | AT patriciarmrocco nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT pedrolsilva nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT fernandafcruz nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT paulofgmmtierno nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT eucirrabello nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT jefitoncordeirojunior nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT firminohaag nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT renataedeavila nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT joanadgdasilva nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT marianamsmamede nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT konradsbuchele nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT luizcvbarbosa nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT annaccabral nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT antonioafjunqueira nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT joaoaaraujofilho nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT luciannaatjdacosta nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT pedropmalvarenga nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT alexandresmoura nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT ricardocarajeleascow nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT mirellacdeoliveira nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT robertagfsilva nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT cynthiarpsoares nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT anapaulasmfernandes nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT flavioguimaraesfonseca nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT vidyleisonnevescamargos nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT juliadesouzareis nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT klebergfranchini nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT ronirrluiz nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT sirleimorais nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT carlossverdloff nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT camilamarinellimartins nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT nathanesfelix nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT paulamattossilva nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT carolinembnogueira nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT dayeneafcaldeira nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT paolopelosi nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT paolopelosi nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial AT joserlapaesilva nitazoxanideinpatientshospitalizedwithcovid19pneumoniaamulticentrerandomizeddoubleblindplacebocontrolledtrial |