Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19
Authors: Gavin D. Perkins, Chen Ji, Bronwen A. Connolly, Keith Couper, Ranjit Lall, J. Kenneth Baillie, Judy M. Bradley, Paul Dark, Chirag Dave, Anthony De Soyza, Anna V. Dennis, Anne Devrell, Sara Fairbairn, Hakim Ghani, Ellen A. Gorman, Christopher A. 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 E. Regan, Clare Ross, Anthony J. Rostron, Mohammad Saim, Anita K. Simonds, Emma Skilton, Nigel Stallard, Michael Steiner, Rama Vancheeswaran, Joyce Yeung, Daniel F. McAuley, Nick Duffy, Martin Kelly, Donal Concannon, Kathryn Ferguson, Declan McClintock, Rajeev Jha, Vinodh Krishnamurthy, Stephen O’Farrell, Cecilia O’Kane, Clare Ross, Richard D Turner, Serge Miodragovic, Peter 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 J C McAuley, Richard J Russell, Sarah Diver, Omer Elneima, Wadah Ibrahim, Ahmed Yousuf, Sarah Edwards, Mohammad Saim, Bridget Hopkins, Lisa Kelly, Daniel Lenton, Helen Shackleford, Laura Thrasyvoulou, Heather Willis, Sara Fairbairn, Chris Green, Mamta Patel, Lucie Linhartova, 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 Crooks, Kayleigh Brindle, Shoaib Faruqi, Rachel Flockton, Emma Pinder, Susannah Thackray-Nocera, Keji Dalemo, James Doidge, Julia Edwards, Jonathon Douse, Stephanie Bell, Bally Purewal, Cathleen Chabo, Carol Buckman, Deborah Beeby, Georgina Gray, Rebecca Francis, Vanessa Rivers, Matthew Burton, Nicholas Innes, Sandy Ghattas, Rana Rabbani, Venkat Mahadevan, Venkateswaran Mahadevan, Alastair Green, Ben Burton, Christian Hacon, Elva Wilhelmsen, Paul R Hughes, Kai Lee, Richard Lowsby, Laurence Baker, Perry Board, Varun Chauhan, Sheron Clarke, Duncan Fullerton, Claire Gabriel, Tom Houston, Diana Lees, Robert Normanton, Katherine Pagett, Sarah Thornley, Harriet Wright, Alison McMillan, Marta Babores, Xiang Lee, Thapas Nagarajan, Maureen Holland, Thomas Sanctuary, Richard Innes, Simon Fletcher, Nita Sehgal, Tracy Duncan, Justine Pooley, Emma Watkins, Harmesh Moudgil, Mandy Carnahan, Denise Donaldson, Deepak Rao, Chia L Tey, Lynette Linkson, Tom Buttle, Jennifer Vidler, Nicola Griffiths, Alexander Hicks, Hitasha Rupani, Afaq Alfridi, Debi Barns, Elena Cowan, Mini David, Alex Darbyshire, Ben Giles, Claire Roberts, Claudia Lameirinhas, Daniel Neville, Ejaz Hossain, Fiona Thompson, Helena Edwards, Jen Naftel, Jonathan Winter, Kate Burrows, Laura Wiffen, Lauren Fox, Lisa Murray, Liz Hawes, Madhu Mamman, Maria Moon, Marie White, Megan Rowley, Nina Szarazova, Sally Gosling, Simon Cooper, Sonia Baryschpolec, Sophie Arndtz, Yasmin H-Davies, Yazeed Abed El Khaleq, Zoe Garner, Siyamini Vythilingam, Yingjja Yang, Dhruv Parekh, Shyam Madathil, Jaimin Patel, Colin Bergin, Michelle Bates, Christopher McGhee, Daniella Lynch, Khushpreet Bhandal, Kyriaki Tsakiridou, Amy Bamford, Lauren Cooper, Tony Whitehouse, Tonny Veenith, Elliott Forster, Steph Lane, Nick Adams, Sonia MacDonald, Sana Manan, Sebastian Lugg, Peer A Shah, Emily McKemey, Louise Crowley, Gulfam Mussawar, Atena Gogokhia, Simon Gompertz, Catherine Snelson, Tessa Oelofse, Jeremy Wilson, Mansoor Bangash, Syed S Huq, Farrukh Rauf, Davinder Dosanjh, Natasha Salmon, Joyce Tengende, Kay F Senior, Brendan Cooper, Benjamin Sutton, Ian Woolhouse, Anjali Crawshaw, Richard Thompson, Patricia Glynn, Jon Naylor, Joseph Alderman, Minesh Chotalia, Martin Le Breuilly, Nicholas Talbot, Gregory Packer, Chris Carlin, Dan Harvey, Alasdair Gray, Manish Gautam, Ingeborg Welters, David O Hamilton, Hassan Burhan, Karl Hunter, Brian Johnston, Maria Lopez, Catherine Lowe, Suleman Mulla, Jaime F Roman, David Shaw, Alicia Waite, Victoria Waugh, Karen Williams, Anita K Simonds, Kate C Tatham, Ethel Black, Shaman Jhanji, Georges Ng Man Kwong, Ben Messer, Anthony De-Soyza, Paul McAlinden, Sophie D West, Vikram Anumakonda, Paul Dark, Liam McMorrow, Tracy Marsden, Nicola Proudfoot, Bethan Charles, Jessica Pendlebury, Bethan Blackledge, Alice Harvey, Karen Knowles, Reece Doonan, Stephanie Lee, Jane Perez, Melanie Slaughter, Melanie Taylor, Victoria Thomas, Emma Hardy, Nawar Bakerly, Laura Catlow, Nasir Majeed, Dan Horner, Liaquat Ali, Dorothy Hutchinson, Liz Fuller, James Dodd, Rahul Bhatnagar, Amelia Clive, Huzaifa Adamali, Anna Bibby, Daniel Higbee, Hugh Welch, Emma Gendall, Louise Staddon, Anna Morley, Sam Clarke, Kerry Smith, Emily Perry, Naomi Rippon, Louise Jennings, Louise Solomon, Karen Alloway, Hannah Lee, Victoria Sandrey, Kirstie Bradburn, Alice Milne, Elizabeth Goff, Rachel Williams, Mohammed Ahmed, Susannah Bloch, Ahmed Zaki, Alistair Roy, Anthony Rostron, Lindsey Woods, Fiona Wakinshaw, Pamela Bainbridge, Peter Hersey, Mark Carpenter, Claire Leech, Laura O'Connor, Andrew Morrison, Elaine Rodgers, Paul McAndrew, Gary Lear, Jim Coates, Maxwell Richardson, David Smith, William Green, Sarah Murray, Christopher Pennington, Huan De Wong, David Land, Helen Wheeler, Matt Harvey, Mark Watson, Michael Brown, Ben Irving, Julie Bigg, Mae Felongco, Joe Mackenzie, Devesh Dhasmana, Rob Thompson, Patrick Lui, Fiona Adam, Fleur Davey, Julie Penman, Amanda McGregor, Patricia Cochrane, Korah Shalan, Will Bozic, Jaclyn Brown, John Carey, Claire Daffern, Emily Dight, Matthew Gane, Belinder Ghuman, Jo Grummett, Johnny Guck, Louisa Hamilton, Cat Hill, Maddy Hill, Chockalingam Muthiah, Emma Padfield, Jeskaran Rai, Kerry Raynes, Greg Scott, Emily Stimpson, Natalie Strickland, Adrian Willis, Jill Wood, Ben Attwood, Inderjit Atwal, Penny Parsons, Rama Vancheeswaran, Shruthi Konda, Yadee M M Myint, Meera Mehta, Ambreen Muhammad, Alessio Navarro, Adam Rochester, Saul Sundayi, Manish Patel, Andrew Smith, Colin Stewart, Matthew Tate, Erin McGarry, Claire (Rebecca) Pearson, Berni Walsh, Lynn Glass, Karen Black, Suzanne Clements, Rosalind Boyle, Chloe MacDonald, Leigh Hamilton, Gayle Moreland, Raymond Hamill, Harsha Reddy, Sara Smuts, Andrew Bentley
Journal: JAMA (2022)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). <h3>Main Outcomes and Measures</h3> The primary outcome was a composite of tracheal intubation or mortality within 30 days. <h3>Results</h3> 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%],<i>P</i> = .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%],<i>P</i> = .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. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> isrctn.org Identifier:ISRCTN16912075