Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial

Abstract

Importance: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial.

Objective: To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs).

Design, setting, and participants: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022.

Interventions: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354).

Main outcomes and measures: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events.

Results: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group.

Conclusions and relevance: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality.

Trial registration: ClinicalTrials.gov Identifier: NCT04468126.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Frat reported receiving grants from the French Ministry of Health and Fisher & Paykel Healthcare during the conduct of the study and personal fees and nonfinancial support from Fisher & Paykel Healthcare and SOS Oxygène outside the submitted work. Dr Coudroy reported receiving grants from the European Respiratory Society and the French Intensive Care Society, and travel expense coverage to attend scientific meetings from Fisher & Paykel Healthcare and Merck Sharp & Dohme. Dr Ehrmann reported receiving personal fees, grants, and nonfinancial support from Fisher & Paykel Healthcare and Aerogen Ltd. Dr Auchabie reported receiving grants from the French Ministry of Health. Dr Demoule reported receiving personal fees from Respinor, Baxter, Fisher & Paykel Healthcare, Lungpacer, Lowenstein, Getinge, Gilead, and Mindray; grants from the French Ministry of Health; and nonfinancial support from Philips. Dr Terzi reported receiving personal fees from Pfizer. Dr Carteaux reported receiving personal fees from Dräger, Medtronic, and Lowenstein and nonfinancial support from Air Liquide Medical System. Dr Beloncle reported receiving nonfinancial support from GE Healthcare and Covidien, travel expenses from Draeger, and personal fees from Lowenstein. Dr Nay reported receiving personal fees for lectures from Fisher & Paykel Healthcare. Dr Ragot reported receiving grants from the French Ministry of Health and Fisher & Paykel Healthcare. Dr Thille reported receiving travel expense coverage to attend scientific meetings and payment for lectures from Fisher & Paykel Healthcare, Covidien, Maquet-Getinge, Dräger Medical, and GE Healthcare. No other disclosures were reported.

Figures

Figure 1.. Flow of Patients in the SOHO-COVID Trial

Fio2 indicates fraction of inspired oxygen; Paco2, partial pressure of arterial carbon dioxide. aAfter April 27, 2021, inclusion criteria were broadened with the aim of including patients with silent hypoxemia having a low respiratory rate. bA total of 389 patients in the original SOHO trial (with stratification on immunosuppression status) and 393 in the ancillary SOHO-COVID trial (with stratification on COVID-19 status and respiratory rate).

Figure 2.. Kaplan-Meier Plot of the Cumulative Incidence of Mortality (Primary Outcome) and Intubation (Secondary Outcome) From Randomization to Day 28

The median observation time was 28 days (IQR, 28-28) in all treatment groups.