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0 0.5 1 1.5 2+ Mortality -3% Improvement Relative Risk Ventilation -16% ICU admission 9% ICU time -12% Hospitalization time -10% N-acetylcysteine  de Alencar et al.  LATE TREATMENT  DB RCT Is late treatment with N-acetylcysteine beneficial for COVID-19? Double-blind RCT 135 patients in Brazil (April - May 2020) No significant difference in outcomes seen de Alencar et al., Clinical Infectious.., Sep 2020 Favors N-acetylcysteine Favors control

Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)

de Alencar et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1443
Sep 2020  
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14th treatment shown to reduce risk in February 2021
*, now known with p = 0.000034 from 24 studies, recognized in 3 countries.
Lower risk for mortality, hospitalization, and cases.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-356
risk of death, 2.6% higher, RR 1.03, p = 0.94, treatment 9 of 67 (13.4%), control 9 of 68 (13.2%), odds ratio converted to relative risk.
risk of mechanical ventilation, 16.0% higher, RR 1.16, p = 0.64, treatment 16 of 67 (23.9%), control 14 of 68 (20.6%), odds ratio converted to relative risk.
risk of ICU admission, 8.5% lower, RR 0.91, p = 0.65, treatment 29 of 67 (43.3%), control 32 of 68 (47.1%), NNT 26, odds ratio converted to relative risk.
ICU time, 12.5% higher, relative time 1.12, p = 0.56, treatment 67, control 68.
hospitalization time, 10.0% higher, relative time 1.10, p = 0.87, treatment 67, control 68.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
de Alencar et al., 23 Sep 2020, Double Blind Randomized Controlled Trial, placebo-controlled, Brazil, peer-reviewed, median age 59.0, 65 authors, study period 10 April, 2020 - 25 May, 2020, average treatment delay 7.0 days.
This PaperN-acetylcys..All
Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)
Julio Cesar Garcia De Alencar, Claudia De Lucena Moreira, Alicia Dudy Müller, Cleuber Esteves Chaves, Marina Akemi Fukuhara, Elizabeth Aparecida Da Silva, Maria De Fátima Silva Miyamoto, Vanusa Barbosa Pinto, Cauê Gasparotto Bueno, Felippe Lazar Neto, Luz Marina Gomez Gomez, Maria Clara Saad Menezes, Julio Flavio Meirelles Marchini, Lucas Oliveira Marino, Rodrigo Antônio Brandão Neto, Heraldo Possolo Souza, Fernando Salvetti Valente, Hassan Rahhal, Juliana Batista Rodrigues Pereira, Eduardo Messias Hirano Padrão, Annelise Passos Bispos Wanderley, Bruno Marques, Luz Marina Gomez Gomez, Edwin Albert D’souza, Arthur Petrillo Bellintani, Rodrigo Cezar Miléo, Rodrigo Werner Toccoli, Fernanda Máximo Fonseca E Silva, João Martelleto Baptista, Marcelo De Oliveira Silva, Giovanna Babikian Costa, Rafael Berenguer Luna, Henrique Tibucheski Dos Santos, Mariana Mendes Gonçalves Cimatti De Calasans, Marcelo Petrof Sanches, Diego Juniti Takamune, Luiza Boscolo, Pedro Antonio Araújo Simões, Manuela Cristina Adsuara Pandolfi, Beatriz Larios Fantinatti, Gabriel Travessini, Matheus Finardi Lima De Faria, Ligia Trombetta Lima, Bianca Ruiz Nicolao, Gabriel De Paula Maroni Escudeiro, João Pedro Afonso Nascimento, Bruna Tolentino Caldeira, Laura De Góes Campos, Vitor Macedo Brito Medeiros, Tales Cabral Monsalvarga, Isabela Harumi Omori, Diogo Visconti Guidotte, Alexandre Lemos Bortolotto, Rodrigo De Souza Abreu, Nilo Arthur Bezerra Martins, Carlos Eduardo Umehara Juck, Lucas De Oliveira Utiyama, Felipe Mouzo Bortoleto, Renan Dourado Tinel, Gabriel Martinez Andreola, Natalia Paula Cardoso, Osvaldo Santistevan Claure, João Vitor Ziroldo Lopes, Sabrina Correa Da Costa Ribeiro
Clinical Infectious Diseases, doi:10.1093/cid/ciaa1443
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 . 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 <94% or respiratory rate >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 ( br/rg/RBR-8969zg/).
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Late treatment
is less effective
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