1. Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)
- Author
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de Alencar, Julio Cesar Garcia, Moreira, Claudia de Lucena, Müller, Alicia Dudy, Chaves, Cleuber Esteves, Fukuhara, Marina Akemi, da Silva, Elizabeth Aparecida, Miyamoto, Maria de Fátima Silva, Pinto, Vanusa Barbosa, Bueno, Cauê Gasparotto, Lazar Neto, Felippe, Gomez Gomez, Luz Marina, Menezes, Maria Clara Saad, Marchini, Julio Flavio Meirelles, Marino, Lucas Oliveira, Brandão Neto, Rodrigo Antônio, Souza, Heraldo Possolo, Valente, Fernando Salvetti, Rahhal, Hassan, Pereira, Juliana Batista Rodrigues, Padrão, Eduardo Messias Hirano, Wanderley, Annelise Passos Bispos, Marques, Bruno, Gomez, Luz Marina Gomez, D’Souza, Edwin Albert, Bellintani, Arthur Petrillo, Miléo, Rodrigo Cezar, Toccoli, Rodrigo Werner, Silva, Fernanda Máximo Fonseca e, Baptista, João Martelleto, Silva, Marcelo de Oliveira, Costa, Giovanna Babikian, Luna, Rafael Berenguer, dos Santos, Henrique Tibucheski, De Calasans, Mariana Mendes Gonçalves Cimatti, Sanches, Marcelo Petrof, Takamune, Diego Juniti, Boscolo, Luiza, Simões, Pedro Antonio Araújo, Pandolfi, Manuela Cristina Adsuara, Fantinatti, Beatriz Larios, Travessini, Gabriel, de Faria, Matheus Finardi Lima, Lima, Ligia Trombetta, Nicolao, Bianca Ruiz, Escudeiro, Gabriel de Paula Maroni, Nascimento, João Pedro Afonso, Caldeira, Bruna Tolentino, Campos, Laura de Góes, Medeiros, Vitor Macedo Brito, Monsalvarga, Tales Cabral, Omori, Isabela Harumi, Guidotte, Diogo Visconti, Bortolotto, Alexandre Lemos, Abreu, Rodrigo de Souza, Martins, Nilo Arthur Bezerra, Juck, Carlos Eduardo Umehara, Utiyama, Lucas de Oliveira, Bortoleto, Felipe Mouzo, Tinel, Renan Dourado, Andreola, Gabriel Martinez, Cardoso, Natalia Paula, Claure, Osvaldo Santistevan, Lopes, João Vitor Ziroldo, and da Costa Ribeiro, Sabrina Correa
- Subjects
0301 basic medicine ,Microbiology (medical) ,Mechanical ventilation ,business.industry ,medicine.medical_treatment ,Placebo-controlled study ,Emergency department ,Intensive care unit ,law.invention ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Infectious Diseases ,Respiratory failure ,law ,Anesthesia ,medicine ,Clinical endpoint ,030212 general & internal medicine ,Respiratory system ,business - Abstract
Background A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19). Methods This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation 24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. Results Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. Conclusions Administration of NAC in high doses did not affect the evolution of severe COVID-19. Clinical Trials Registration Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).
- Published
- 2020
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