Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial
MD, PhD Patricia R M Rocco, PhD Pedro Leme Silva, MD, PhD Fernanda F Cruz, Marco Antonio, MD, MSc C M Junior, MD Paulo F G M M Tierno, MD, PhD Marcos A Moura, Frederico G Luís, Cristiano C De Oliveira, Ezequiel A Dos Lima, Walter F Santos, Ana Junior, S M Paula, Kleber G Fernandes, Erick Franchini, Nara F Magri, José De Moraes, José Mário, Melanie N Gonçalves, Ivonise S Dos Carbonieri, Natália F Santos, Paula V M Paes, Raissa P Maciel, Alex F Rocha, Pedro Augusto De Carvalho, José Alves, Paolo Luiz, Artur T Modena, Daniela B B Cordeiro, Rafael E Trivella, Ronir R Marques, Jose Roberto Pelosi, Lapa, ; Luís, MD Frederico G De Oliveira, ; Cristiano, Cristiano Cleidson Lima, MSc Ezequiel A Dos Santos, BDS Walter F Junior, Ana Paula, PhD S M Fernandes, ; Kleber, MD, PhD G Franchini, Elisabete Erick Magri, MD Nara F De Moraes, J Gonçalves, MD Melanie N Carbonieri, BDS Ivonise S Dos Santos, MSc Natália F Paes, Paula V M Maciel, PhD Raissa Prado Rocha, PhD Alex F De Carvalho, PhD Pedro Augusto Alves, José Roberto Luiz, PhD Proença Modena, PhD Artur T Cordeiro, PhD Daniela B B Trivella, Rafael E Marques, ; Ronir, PhD Ronir R Luiz, MD, FERS Paolo Pelosi, ; Jose, Roberto Lapa, Prof Patricia Rieken, MD Macedo Rocco, Prof R M Patricia, Rocco, ; Paula, MD V M Maciel, PhD Rafael E Marques, Jose Roberto Lapa, MD, PhD Silva, PhD Pedro Leme Silva, MD, PhD). Fernanda Ferreira Cruz, Prof Marcus Conde, Prof Faria Hugo Caire, MD, PhD Neto, Prof Hugo Oliveira, Cássia Lisboa Braga, Soraia Carvalho Abreu, André Benedito Da Silva, Heloísa Leal Setta, Leila Muniz De Almeida Spelta, Raggio Ronir, Albert Sabin, São Caetano, : Marco, Antonio Cezario De Melo Junior, Ariane Da, Roseli Bernardo Mendes, Marli Monteiro, Hospital Municipal de Antonio Barueri, Dr Francisco Moran, Paulo Fernando, Guimarães Morando, Marzocchi Tierno, Alves Tonelli, Fernando Carvalho Sacchetin, Igor Silva, Fernandes Machado, Silva Marques, Patricia Carvalho, Pereira Beloti, Ana Luiza, Borges Cabral, Leandro Oliveira De Morais, Ivonise Sampaio, Dos Santos, Paulo Ricardo, Ramos Cardoso, Dina Laine Coutinho, Castro Azevedo, Katherine Dos, Santos Borges, Steyce Raphaelle, Morais Nunes, Zildene Dos Santos, Moreira Bitencourt, Lívia Batista, Silva Carvalho, Marcela Silva, Ferreira Fiadeiro, Lissandra Lima, Kelly Cristine, Barros Melo, Patrícia Augusto Nunes, Cananda Ferreira Cavalcante, Christiane Silva Pinheiro, Moises Batista De Azevedo, Michele Catherine Salles Bueno, Cristina Vermelho, Freitas Junior, Paula Veronica, Martini Maciel, Silvia Ferreira De Souza, Luis Cleverson, Rodrigo Rodrigues, Leandro Jose Sarago De Moura, Lucas De, Amanda Lima, Agra Loos, Renart Larry Takada, Gustavo Jose Goda Fernández, Senechal Le, Marta Salatino, Gomes Da Silva, Ana Paula Fernandes, Alex Fiorini De Carvalho, Leopoldo Ferreira, Marques Machado, Rafael Elias Marques, Alexander Borin, Laís D Coimbra, Gabriela Souza, Stefanie Muraro, Juliana H C Smetana, Fabrício F Naciuk, Matheus Martini, Julia Forato, Leandro O Bortot, Celso E Benedetti, Paulo S Oliveira, Fabiana Granja, Marjorie Bruder, Carlos Sverdloff, Claudia Viana, Vinicius Rezende, Laura Tavares, Regiane Xavier, Luis Bueno, Sirlei Siani, Ricardo Cassiano, PharmD Magalhães De Oliveira Berto, MD. Lahmann
doi:10.1183/13993003.03725-2020)
Take home message This was the first study to evaluate the effect of early nitazoxanide therapy in mild Covid-19. Nitazoxanide did not accelerate symptom resolution after 5 days of therapy but did reduce viral load significantly with no serious adverse events.
Conflict of interest Dr. Rocco reports personal fees from SANOFI as a DSMB member. The other authors declare no competing interests.
Supplementary Appendix to the Manuscript Early use of nitazoxanide in mild Covid-19 disease: randomized, placebocontrolled trial FBS, 1% L-glutamine and 1% penicillin/streptomycin, and maintained as described above.
Virus and preparation of viral stock The SARS-CoV- Upon registration of a patient in the system, a unique trial identifier and barcode number (for laboratory tests) were generated and the patient was randomly allocated into group A or B, as mentioned above. Forms within the system were divided into sections that allowed registration were given a thermometer and instructed to complete a self-administered questionnaire, which consisted of a list of symptoms and scales on which to record their intensity on each day of therapy (Table S2 ). Patients were also instructed to return to the study site if any adverse event occurred. One day before completion of therapy, patients received a phone call to remind them to come back to the study site on the next day for final evaluation. Every included patient was followed according to the following data collection plan: 1. Clinical evaluation (fever, dry cough, fatigue): daily during the course of therapy (via selfadministered questionnaire).
RNA extraction and real-time polymerase chain reaction (qPCR) Nasopharyngeal swab samples obtained from each patient were collected in a single..
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Por Favor, utilize o termômetro e informe a sua temperatura corporal? ( ) Menor que 37º ( ) 37º a
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'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>Nitazoxanide is widely available and '
'exerts broad-spectrum antiviral activity <jats:italic>in vitro</jats:italic>. However, there '
'is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) '
'infection.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In a '
'multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up '
'to 3\u2005days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever '
'and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse '
'transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either '
'nitazoxanide (500\u2005mg) or placebo, three times daily, for 5\u2005days. The primary '
'outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory '
'tests, serum biomarkers of inflammation and hospitalisation rate. Adverse events were also '
'assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>From June 8 to '
'August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) '
'were analysed. Median (interquartile range) time from symptom onset to first dose of study '
'drug was 5 (4–5)\u2005days. At the 5-day study visit, symptom resolution did not differ '
'between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in '
'29.9% of patients in the nitazoxanide arm <jats:italic>versus</jats:italic> 18.2% in the '
'placebo arm (p=0.009). Viral load was reduced after nitazoxanide compared to placebo '
'(p=0.006). The percentage viral load reduction from onset to end of therapy was higher with '
'nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not '
'significantly different. No serious adverse events were '
'observed.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In '
'patients with mild COVID-19, symptom resolution did not differ between nitazoxanide and '
'placebo groups after 5\u2005days of therapy. However, early nitazoxanide therapy was safe and '
'reduced viral load significantly.</jats:p></jats:sec>',
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