High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure
Authors:   RENOVATE Investigators and the BRICNet Authors, Francio Fabiano , Weigert Renata Monteiro , Mattei Edna Daldania Biolchi , Grion Cintia Magalhaes Carvalho , Festti Josiane , Mezzaroba Ana Luiza , Serpa Neto Ary , Timenetsky Karina T. , Nogueira Adriana Maria Simoes Orfao , Brito Marcus Vinicius Camargo , Lima Iuri Dheloi Oliveira , Dona Rodrigo Alexandre , Mafra Marina Monica Bahl , Starke Ana Carolina , Lisboa Thiago , Fachini Caroline , Torelly André , Biondi Rodrigo Santos , Souza Andre Luiz Nascimento , Fernandes Anderson Luiz Mendes , Araujo Gustavo Neves , Ponte Vicente , Antunes Maria Helena Moraes , Cardoso Fabio Fernandes Cardoso , Poersch Alice Bertotto , Ramires Yuri Carlotto , Moura Lúcio Roberto Requiao , Peruzzo Maria Bethania , Sposito Jonas , Piekala Daniele Martins , Wawrzeniak Iuri Christmann , Fialkow Léa , Dutra Marcela , Mazera Maiara Suelen , Martins Cassia Pimenta Barufi , Freitas Daniela Helena Machado , Sanches Luciana Coelho , Pereira Maísa Guimarães de Castro , Cunha Mariana Regina , Maia Israel S. , Kawano-Dourado Letícia , Tramujas Lucas , de Oliveira Neymar Elias , Souza Rafael Naoki , Signorini Dhaisi Faustino , Pincelli Mariangela Pimentel , Zandonai Cássio Luis , Blasius Regiane Tamires , Freires Fabrício , Ferreira Vanessa Marques , Romano Marcelo Luz Pereira , Miura Mieko Claudia , de Censo Caroline Maschio , Caser Eliana Bernadete , Silva Betania , Santos Bonomo Daniela Correia , Arraes Jussara Alencar , de Alencar Filho Meton Soares , Álvares Horta Jacques Gabriel , Oliveira Déborah Campos , Boschi Emerson , Costa Rafael Lessa , Westphal Glauco Adrieno , Ramos Juliano , Lacerda Fábio Holanda , Filho Conrado Roberto Hoffmann , Pinheiro Bruno Valle , de Andrade Neumamm Leonardo Bugarin , Guimarães Júnior Mário Roberto Rezende , de Souza Davi Tamamaru , Ferreira Juliana Carvalho , Ohe Louis Nakayama , Schettini Daniel Almeida , Thompson Marlus Muri , de Oliveira Maria Cristina França , Veiga Viviane Cordeiro , Negrelli Karina L. , Santos Renato H. N. , Damiani Lucas , Gurgel Rodrigo M. , Gomes Samara P. C. , Lima Lucas M. , Miranda Tamiris A. , Laranjeira Ligia N. , de Barros e Silva Pedro Gabriel Melo , Machado Flávia R. , Fitzgerald Mark , Bosse Anna , Marion Joe , Carvalho Carlos Roberto Ribeiro , Brochard Laurent , Lewis Roger J. , Biasi Cavalcanti Alexandre 
Published: December 2024

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