High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure
RENOVATE Investigators and the BRICNet Authors, Fabiano Frâncio, Renata Monteiro Weigert, Edna Daldania Biolchi Mattei, Cíntia Magalhães Carvalho Grion, Josiane Festti, Ana Luiza Mezzaroba, Ary Serpa Neto, Karina Tavares Timenetsky, Adriana Maria Simoes Orfao Nogueira, Marcus Vinicius Camargo Brito, Iuri Dheloi Oliveira Lima, Rodrigo Alexandre Dona, Marina Monica Bahl Mafra, Ana Carolina Starke, Thiago Lisboa, Caroline Fachini, André P. Torelly, Rodrigo Biondi, Adriano Lopes de Souza, Anderson Luiz Mendes Fernandes, Gustavo Neves de Araújo, Vicente Ponte, Maria Helena Moraes Antunes, Fabio Fernandes Cardoso Cardoso, Alice Bertotto Poersch, Yuri Carlotto Ramires, Lúcio Requião‐Moura, Maria Bethania Peruzzo, Jonas Sposito, Daniele Martins Piekala, Iuri Christmann Wawrzeniak, Léa Fialkow, Marcela Dutra, Maiara Suelen Mazera, Cassia P. B. Martins, Daniela Helena Machado Freitas, Luciana Coelho Sanches, Márcio Pereira, Mariana Regina da Cunha, Israel Silva Maia, Letícia Kawano-Dourado, Lucas Tramujas, Neymar Elias de Oliveira, Rafael Naoki Souza, D. F. Signorini, Mariângela Pimentel Pincelli, Cássio Luis Zandonai, Regiane Tamires Blasius, Fabricio Jocundo Calado Freires, Vanessa Marques Ferreira, Marcelo Luz Pereira Romano, Mieko Cláudia Miura, Caroline Maschio de Censo, Eliana Bernadete Caser, Beatriz Mendes Abib da Silva, Daniela Correia Santos Bonomo, Jussara Alencar Arraes, Meton Soares de Alencar Filho, Jacques Gabriel Álvares Horta, Deborah Campos Oliveira, Emerson Boschi, Rafael Lessa da Costa, Glauco Adrieno Westphal, Juliano Ramos, Fábio Holanda Lacerda, Conrado Roberto Hoffmann Filho, Bruno Valle Pinheiro, Leonardo Bugarin de Andrade Neumamm, Mário Roberto Rezende Guimarães Júnior, Davi Tamamaru de Souza, Juliana Carvalho Ferreira, Louis Nakayama Ohe, Daniel Almeida Schettini, Marlus Muri Thompson, Maria Cristina França de Oliveira, Viviane Cordeiro Veiga, Karina Leal Negrelli, Renato Hideo Nakagawa Santos, Lucas Petri Damiani, Rodrigo M. Gurgel, Samara P. C. Gomes, Lucas Martins de Lima, Tamiris Abait Miranda, Lígia Nasi Laranjeira, Pedro Gabriel Melo de Barros e Silva, Flávia Ribeiro Machado, Mark Fitzgerald, Anna Bosse, Joe Marion, Carlos Roberto Ribeiro de Carvalho, Laurent Brochard, Roger J. Lewis, Alexandre Biasi Cavalcanti
Abstract
Importance: High-flow nasal oxygen (HFNO) and noninvasive ventilation (NIV) are commonly used respiratory support therapies for patients with acute respiratory failure (ARF). Objective: To assess whether HFNO is noninferior to NIV on the rates of endotracheal intubation or death at 7 days in 5 patient groups with ARF. Design, Setting, and Participants: This noninferiority, randomized clinical trial enrolled hospitalized adults (aged ≥18 years; classified as 5 patient groups with ARF: nonimmunocompromised with hypoxemia, immunocompromised with hypoxemia, chronic obstructive pulmonary disease [COPD] exacerbation with respiratory acidosis, acute cardiogenic pulmonary edema [ACPE], or hypoxemic COVID-19, which was added as a separate group on June 26, 2023) at 33 hospitals in Brazil between November 2019 and November 2023 (final follow-up: April 26, 2024). Interventions: High-flow nasal oxygen (n = 883) or NIV (n = 883). Main Outcomes and Measures: The primary outcome was endotracheal intubation or death within 7 days assessed using a bayesian hierarchical model with dynamic borrowing across patient groups. Noninferiority was defined by a posterior probability of 0.992 or greater for an odds ratio (OR) less than 1.55. Results: Among 1800 patients, 1766 completed the study (mean age, 64 [SD, 17] years; 707 [40%] were women). The primary outcome of endotracheal intubation or death at 7 days occurred in 39% (344/883) in the HFNO group vs 38% (336/883) in the NIV group. In the immunocompromised with hypoxemia patient group, the primary outcome occurred in 57.1% (16/28) in the HFNO group vs 36.4% (8/22) in the NIV group; enrollment was stopped for futility (final OR, 1.07; 95% credible interval [CrI], 0.81-1.39; noninferiority posterior probability [NPP], 0.989). In the nonimmunocompromised with hypoxemia group, the primary outcome occurred in 32.5% (81/249) in the HFNO group vs 33.1% (78/236) in the NIV group (OR, 1.02 [95% CrI, 0.81-1.26]; NPP, 0.999). In the ACPE group, the primary outcome occurred in 10.3% (14/136) in the HFNO group vs 21.3% (29/136) in the NIV group (OR, 0.97 [95% CrI, 0.73-1.23]; NPP, 0.997). In the hypoxemic COVID-19 group, the primary outcome occurred in 51.3% (223/435) in the HFNO group vs 47.0% (210/447) in the NIV group (OR, 1.13 [95% CrI, 0.94-1.38]; NPP, 0.997). In the COPD exacerbation with respiratory acidosis group, the primary outcome occurred in 28.6% (10/35) in the HFNO group vs 26.2% (11/42) in the NIV group (OR, 1.05 [95% CrI, 0.79-1.36]; NPP, 0.992). However, a post hoc analysis without dynamic borrowing across the 5 ARF patient groups revealed some qualitatively different results in patients with COPD, immunocompromised patients, and patients with ACPE. The incidence of serious adverse events was similar (9.4% of patients in HFNO group vs 9.9% in NIV group). Conclusions and Relevance: Compared with NIV, HFNO met prespecified criteria for noninferiority for the primary outcome of endotracheal intubation or death within 7 days in 4 of the 5 patient groups with ARF. However, the small sample sizes in some patient groups and the sensitivity of the findings to the choice of analysis model suggests the need for further study in patients with COPD, immunocompromised patients, and patients with ACPE. Trial Registration: ClinicalTrials.gov Identifier: NCT03643939.