Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19
Gavin D. Perkins, Chen Ji, Bronwen Connolly, Keith Couper, Ranjit Lall, J. Kenneth Baillie, Judy Bradley, Paul Dark, Chirag Dave, Anthony De Soyza, Anna Dennis, Anne Devrell, Sara Fairbairn, Hakim Ghani, Ellen Gorman, Christopher Green, Nicholas Hart, Siew Wan Hee, Zoe Kimbley, Shyam Madathil, Nicola McGowan, Benjamin Messer, Jay Naisbitt, Chloe Norman, Dhruv Parekh, Emma M Parkin, Jaimin Patel, Scott Regan, Clare Ross, Anthony Rostron, Mohammad Saim, Anita K. Simonds, Emma Skilton, Nigel Stallard, Michael Steiner, Rama Vancheeswaran, Joyce Yeung, Daniel F. McAuley, RECOVERY-RS Collaborators, Nick Duffy, Martin Kelly, Dónal Concannon, Kathryn M. Ferguson, Declan McClintock, Rajeev Jha, Vinodh Krishnamurthy, Stephen O’Farrell, Cecilia O’Kane, Clare Ross, Richard Turner, Serge Miodragovic, Peter C.T. Hawkins, Jessie Welbourne, Colin Wells, Liana Lankester, Samuel D Waddy, Julian Lentaigne, Jay Nesbitt, Sarah Clarke, Catherine Houghton, Devaki O’Riordan, Kate Shepherd, Beth Turnpenny, Rosane Joseph, Michael Steiner, Clare Rossall, Rachel Mundin, Samuele Boschi, Hamish McAuley, Richard Russell, Sarah Diver, Omer Elneima, Wadah Ibrahim, Ahmed Yousuf, Sarah Edwards, Mohammad Saim, Bridget Hopkins, Lisa M. Kelly, Daniel Lenton, Helen Shackleford, Laura Thrasyvoulou, Heather Willis, Sara Fairbairn, Chris Green, Mamta Patel, Lucie Linhartová, Emma Hayton, Amy Chue, Ben Collins, Matt Page, Ed Birkhamshaw, Mary Bellamy, Hollie Bancroft, Emma Gallagher, Pearlene Antoine‐Pitterson, Beth Jones, Safia Begum, Sundip Dhani, Michael G. Crooks, Kayleigh Brindle
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.