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Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory FailureThe HENIVOT Randomized Clinical Trial

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Question  Among patients admitted to the intensive care unit with COVID-19–induced moderate to severe hypoxemic respiratory failure, does early continuous treatment with helmet noninvasive ventilation increase the number of days free of respiratory support at 28 days as compared with high-flow nasal oxygen?

Findings  In this randomized trial that included 109 patients, the median number of days free of respiratory support within 28 days was 20 days in the group that received helmet noninvasive ventilation and 18 days in the group that received high-flow nasal oxygen, a difference that was not statistically significant.

Meaning  Among critically ill patients with moderate to severe hypoxemic respiratory failure due to COVID-19, helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days.

Abstract

Importance  High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.

Objective  To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone.

Design, Setting, and Participants  Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200).

Interventions  Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55).

Main Outcomes and Measures  The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay.

Results  Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, −2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, −21% [95% CI, −38% to −3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, −1% [95% CI, −17% to 15%]; P > .99).

Conclusions and Relevance  Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation.

Trial Registration  ClinicalTrials.gov Identifier: NCT04502576

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Article Information

Corresponding Author: Domenico L. Grieco, MD, Department of Anesthesiology and Intensive Care Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Lgo F Vito, 00168, Rome, Italy (dlgrieco@outlook.it).

Accepted for Publication: March 12, 2021.

Published Online: March 25, 2021. doi:10.1001/jama.2021.4682

Author Contributions: Drs Grieco and Menga had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Grieco, Pintaudi, Dell'Anna, Bocci, De Pascale, Volta, Conti, Maggiore, Antonelli.

Acquisition, analysis, or interpretation of data: Grieco, Menga, Cesarano, Rosà, Spadaro, Bitondo, Montomoli, Falò, Tonetti, Cutuli, Pintaudi, Tanzarella, Piervincenzi, Bongiovanni, Dell’Anna, Delle Cese, Berardi, Carelli, Montini, Bello, Natalini, De Pascale, Velardo, Volta, Ranieri, Antonelli.

Drafting of the manuscript: Grieco, Menga, Cesarano, Pintaudi, Bongiovanni, Dell’Anna, Carelli, Bocci, Natalini, De Pascale, Antonelli.

Critical revision of the manuscript for important intellectual content: Grieco, Menga, Rosà, Spadaro, Bitondo, Montomoli, Falò, Tonetti, Cutuli, Pintaudi, Tanzarella, Piervincenzi, Bongiovanni, Delle Cese, Berardi, Montini, Bello, De Pascale, Velardo, Volta, Ranieri, Conti, Maggiore, Antonelli.

Statistical analysis: Grieco, Montini, De Pascale, Velardo.

Obtained funding: Grieco, Antonelli.

Administrative, technical, or material support: Grieco, Cesarano, Rosà, Spadaro, Bitondo, Pintaudi, Tanzarella, Piervincenzi, Bongiovanni, Dell’Anna, Bocci, Natalini, De Pascale, Antonelli.

Supervision: Grieco, Spadaro, Pintaudi, Piervincenzi, Bongiovanni, Dell’Anna, Bocci, Bello, De Pascale, Volta, Ranieri, Conti, Maggiore, Antonelli.

Conflict of Interest Disclosures: Dr Grieco reported receiving grants from the Italian Society of Anesthesia, Analgesia, and Intensive Care Medicine during the conduct of the study and grants from the European Society of Intensive Care Medicine and GE Healthcare and travel expenses from Maquet, Getinge, and Air Liquide outside the submitted work. Dr Montomoli reported receiving personal fees from Active Medica BV outside the submitted work. Dr Conti reported receiving payments for lectures from Chiesi Pharmaceuticals SpA. Dr Maggiore reported serving as the principal investigator of the RINO trial (ClinicalTrials.gov NCT02107183), which was supported by Fisher and Paykel Healthcare through an institutional grant, and receiving personal fees from Draeger Medical and GE Healthcare outside the submitted work. Dr Antonelli reported receiving personal fees from Maquet, Chiesi, and Air Liquide and grants from GE Healthcare outside the submitted work. No other disclosures were reported.

Funding/Support: The study was funded by a research grant (2017 Merck Sharp & Dohme SRL award) by the Italian Society of Anesthesia, Analgesia, and Intensive Care Medicine.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The COVID-ICU Gemelli Study Group members are listed in Supplement 4.

Data Sharing Statement: See Supplement 5.

Additional Contributions: We are grateful to all intensive care unit physicians, residents, nurses, and personnel from the participating centers, whose sacrifice, efforts, devotion to patients, and passion have made possible this timely report. We are grateful to Jean-Pierre Frat, MD, PhD (Poitiers, France), Oriol Roca, MD, PhD (Barcelona, Spain), and Jordi Mancebo, MD, PhD (Barcelona, Spain), for their contribution as members of the adjudication committee for endotracheal intubation. We are grateful to Cristina Cacciagrano, Emiliano Tizi, and Alberto Noto, MD, for their contribution to study organization. We are grateful to Gabriele Esposito, PD, for Figure 1 drafting. Drs Frat, Roca, and Velardo received a personal fee for their contribution to the study; all others listed did not receive compensation.

Additional Information: The study was endorsed by the Insufficienza Respiratoria Acuta e Assistenza Respiratoria study group of the Italian Society of Anesthesia, Analgesia, and Intensive Care Medicine.

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