An adaptive randomized controlled trial of non-invasive respiratory strategies in acute respiratory failure patients with COVID-19

Perkins, G. D.; Ji, C.; Connolly, B. A.; Couper, K.; Lall, R.; Baillie, J. K.; Bradley, J. M.; Dark, P.; Dave, C.; De Soyza, A.; Dennis, A. V.; Devrell, A.; Fairbairn, S.; Ghani, H.; Gorman, E. A.; Green, C. A.; Hart, N.; Hee, S. W.; Kimbley, Z.; Madathil, S.; McGowan, N.; Messer, B.; Naisbitt, J.; Norman, C.; Parekh, D.; Parkin, E. M.; Patel, J.; Regan, S. E.; Ross, C.; Rostron, A. J.; Saim, M.; Simonds, A. K.; Skilton, E.; Stallard, N.; Steiner, M.; Vancheeswaran, R.; Yeung, J.; McAuley, D. F.; collaborators, Recovery- RS

Background Both continuous positive airway pressure (CPAP) and high-flow nasal oxygenation (HFNO) have been recommended for acute respiratory failure in COVID-19. However, uncertainty exists regarding effectiveness and safety. Methods In the Recovery- Respiratory Support multi-center, three-arm, open-label, adaptive, randomized controlled trial, adult hospitalized patients with acute respiratory failure due to COVID-19, deemed suitable for treatment escalation, were randomly assigned to receive CPAP, HFNO, or conventional oxygen therapy. Comparisons were made between each intervention and conventional oxygen therapy. The primary outcome was a composite of tracheal intubation or mortality within 30-days. Results Over 13-months, 1272 participants were randomized and included in the analysis (380 (29.9%) CPAP; 417 (32.8%) HFNO; 475 (37.3%) conventional oxygen therapy). The need for tracheal intubation or mortality within 30-days was lower in the CPAP group (CPAP 137 of 377 participants (36.3%) vs conventional oxygen therapy 158 of 356 participants (44.4%); unadjusted odds ratio 0.72; 95% CI 0.53 to 0.96, P=0.03). There was no difference between HFNO and conventional oxygen therapy (HFNO 184 of 414 participants (44.4%) vs conventional oxygen therapy 166 of 368 participants (45.1%); unadjusted odds ratio 0.97; 95% CI 0.73 to 1.29, P=0.85). Conclusions CPAP, compared with conventional oxygen therapy, reduced the composite outcome of intubation or death within 30 days of randomisation in hospitalized adults with acute respiratory failure due to COVID-19. There was no effect observed, compared with conventional oxygen therapy, with the use of HFNO. (Funded by the UK National Institute for Health Research; ISRCTN 16912075).