TY - JOUR
T1 - Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19
T2 - The RECOVERY-RS Randomized Clinical Trial
AU - RECOVERY-RS Collaborators
AU - Perkins, Gavin D
AU - Ji, Chen
AU - Connolly, Bronwen A
AU - Couper, Keith
AU - Lall, Ranjit
AU - Baillie, J Kenneth
AU - Bradley, Judy M
AU - Dark, Paul
AU - Dave, Chirag
AU - De Soyza, Anthony
AU - Dennis, Anna V
AU - Devrell, Anne
AU - Fairbairn, Sara
AU - Ghani, Hakim
AU - Gorman, Ellen A
AU - Green, Christopher A
AU - Hart, Nicholas
AU - Hee, Siew Wan
AU - Kimbley, Zoe
AU - Madathil, Shyam
AU - McGowan, Nicola
AU - Messer, Benjamin
AU - Naisbitt, Jay
AU - Norman, Chloe
AU - Parekh, Dhruv
AU - Parkin, Emma M
AU - Patel, Jaimin
AU - Regan, Scott E
AU - Ross, Clare
AU - Rostron, Anthony J
AU - Saim, Mohammad
AU - Simonds, Anita K
AU - Skilton, Emma
AU - Stallard, Nigel
AU - Steiner, Michael
AU - Vancheeswaran, Rama
AU - Yeung, Joyce
AU - McAuley, Daniel F
N1 - Funding Information:
reported being supported by the National Institute for Health Research (NIHR) West Midlands Applied Research Collaboration and serving as co-director of research for the Intensive Care Society until recently (term ended in June 2021). Dr Connolly reported receiving grants from the NIHR; receiving personal fees from Fisher & Paykel Healthcare; and serving as the director of research for the Intensive Care Society. Dr Baillie reported receiving grants from the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the Medical Research Council. Dr Dark reported receiving grants from the Manchester NIHR Biomedical Research Centre and being a national specialty cluster lead for the NIHR. Dr Dave reported receiving personal fees from Chiesi. Dr De Soyza reported being a national specialty cluster lead for the NIHR and receiving personal fees from AstraZeneca, Bayer, Chiesi, Gilead, GlaxoSmithKline, Forest Labs, Novartis, Insmed, Teva, Zambon, and Pfizer. Mrs Devrell reported receiving personal fees from the NIHR. Dr Gorman reported receiving grants from the NIHR and Wellcome Trust. Dr Hart reported receiving a UK Research and Innovation grant from the Medical Research Council; receiving unrestricted grants and equipment from Philips-Respironics, Fisher & Paykel Healthcare, and ResMed; receiving institutional funding for his role on the Philips Global medical advisory board; receiving personal fees from Philips-Respironics, Philips, ResMed, and Fisher & Paykel Healthcare; and receiving financial support from Philips for the development of the Myotrace technology that has a patent approved in Europe and in the US. Dr Hee reported receiving grants from the British Heart Foundation and the NIHR West Midlands Research Design Service. Mr Messer reported receiving personal fees from Fisher & Paykel Healthcare. Dr Parekh reported receiving a UK Research and Innovation grant from the Medical Research Council and receiving grants from the NIHR. Dr Steiner reported receiving personal fees from GlaxoSmithKline. Dr McAuley reported receiving personal fees from GlaxoSmithKline, Boehringer Ingelheim, Bayer, Novartis, Sobi, Eli Lilly, Vir Biotechnology, and Faron Pharmaceuticals; receiving grants from the NIHR, Randox, Wellcome Trust, Innovate UK, the Medical Research Council, and the Northern Ireland Health and Social Research and Development Division; holding a patent for an anti-inflammatory treatment issued to Queen’s University Belfast; and serving as co-director of research for the Intensive Care Society until recently (term ended in June 2021) and as program director for the NIHR Efficacy and Mechanism Evaluation program. No other disclosures were reported.
Funding Information:
The Randomized Evaluation of COVID-19 Therapy–Respiratory Support (RECOVERY-RS) clinical trial was conducted across 48 acute care hospitals in the UK and Jersey. The trial protocol was approved by the London-Brighton and Sussex research ethics committee and the Health Research Authority, sponsored by the University of Warwick, coordinated by the Warwick Clinical Trials Unit, and funded by the National Institute for Health Research. An independent trial steering committee and data and safety monitoring committee provided trial oversight. The RECOVERY-RS trial was conducted in accordance with Good Clinical Practice guidelines, local regulations, and the ethical principles described in the Declaration of Helsinki.12 In keeping with regional regulations, consent from patients or agreement from their family or another surrogate was obtained orally, with a written record maintained by the researcher. The trial protocol has been published.13 The trial protocol and statistical analysis plan appear in Supplement 1.
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/2/8
Y1 - 2022/2/8
N2 - 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.
AB - 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.
KW - Adult
KW - COVID-19/complications
KW - Cannula
KW - Continuous Positive Airway Pressure
KW - Female
KW - Hospital Mortality
KW - Humans
KW - Intubation, Intratracheal/statistics & numerical data
KW - Length of Stay
KW - Male
KW - Middle Aged
KW - Noninvasive Ventilation/methods
KW - Oxygen Inhalation Therapy/methods
KW - Respiratory Insufficiency/etiology
U2 - 10.1001/jama.2022.0028
DO - 10.1001/jama.2022.0028
M3 - Article
C2 - 35072713
VL - 327
SP - 546
EP - 558
JO - Journal of the American Medical Association
JF - Journal of the American Medical Association
SN - 0098-7484
IS - 6
ER -