Original Investigation January 24, 2022

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial

Gavin D. Perkins, Chen Ji, Bronwen A. Connolly, et al

JAMA. Published online January 24, 2022. doi:10.1001/jama.2022.0028

Key Points

Question  What is the effect of initial noninvasive respiratory strategies using continuous positive airway pressure (CPAP) or high-flow nasal oxygen (HFNO), compared with an initial strategy of conventional oxygen therapy, on the risk of tracheal intubation or mortality among hospitalized adults with acute hypoxemic respiratory failure due to COVID-19?

Findings  In this randomized clinical trial of 1273 patients, the composite primary outcome of tracheal intubation or mortality within 30 days occurred in 36% of the patients in the CPAP group compared with 44% in the conventional oxygen therapy group, a difference that was statistically significant, and occurred in 44% in the HFNO group compared with 45% in the conventional oxygen therapy group, a difference that was not significantly different.

Meaning  Among patients with acute hypoxemic respiratory failure and COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy.Abstract

Importance  Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies.

Objective  To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19–related acute hypoxemic respiratory failure.

Design, Setting, and Participants  A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19–related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021.

Interventions  Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475).

Main Outcomes and Measures  The primary outcome was a composite of tracheal intubation or mortality within 30 days.

Results  The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, −8% [95% CI, −15% to −1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, −1% [95% CI, −8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group.

Conclusions and Relevance  Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings.

Trial Registration  isrctn.org Identifier: ISRCTN16912075