Among patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), an initial strategy of continuous positive airway pressure (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 high-flow nasal oxygen (HFNO) compared with conventional oxygen therapy, according to a randomised clinical trial published in JAMA.
Nonetheless, researchers led by Gavin D. Perkins, MD, University of Warwick, Coventry, UK, cautioned that “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,” adding that “given the width of the 95% confidence interval (CI), the trial may have been underpowered to detect small but clinically important treatment effects.”
The trial conducted between April 6, 2020 and May 3, 2021 across 48 acute care hospitals in the UK and Jersey randomised 1,273 hospitalised adults with COVID-19-related acute hypoxemic respiratory failure to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Final follow-up occurred on June 20, 2021. The mean age of the patients was 57.4 years and 66% of them were male. The median time from first COVID-19 symptoms to randomisation was 9 days (interquartile range [IQR], 7.0 to 12.0). The baseline median SpO2 was 93% (IQR, 91%-95%) and FiO2 was 0.60 (IQR, 0.40 to 0.80). In the CPAP group, initial positive end-expiratory pressure was set at a mean of 8.3 cm H2O (95% CI, 8.1 to 8.5 cm H2O). In the HFNO group, initial flow was set at a mean of 52.4 L/min (95% CI, 51.4 to 53.5 L/min).
Meanwhile, treatment crossover occurred in 17.1% of participants (15.3% [58/380] in the CPAP group, 11.5% [48/418] in the HFNO group, and 23.6% [112/475] in the conventional oxygen therapy group). Primary outcome analysis was available for 1,260 patients.
Overall, the requirement for tracheal intubation or mortality within 30 days was significantly lower among patients assigned to CPAP (36.3%; 137 of 377 participants) compared with those assigned to conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, −8% [95% CI, −15% to −1%]; adjusted odds ratio [OR] 0.68 [95% CI 0.48 to 0.94]; P = 0.02), but was not significantly different between patients who received HFNO (44.3%; 184 of 415 participants) and those who were on conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, −1% [95% CI, −8% to 6%]; adjusted OR 0.94 [95% CI 0.68 to 1.29]; P = 0.69).
As for secondary outcomes, the researchers observed a significant difference in the individual incidence of tracheal intubation within 30 days in the CPAP group (33.4% vs 41.3% in the conventional therapy group; absolute difference, −8% [95% CI, −15% to −1%]). However, a significant difference was not observed for the individual incidence of mortality within 30 days in the CPAP group (16.7% vs 19.2% in the conventional therapy group; absolute difference, −3% [95% CI, −8% to 3%]). Compared with conventional oxygen therapy, neither CPAP nor HFNO significantly reduced mortality in the intensive care unit (ICU) or in the hospital.
Additionally, significantly fewer patients in the CPAP group required admission to the ICU compared with participants in the conventional oxygen therapy group (55.4% vs 62.9%, respectively; absolute difference, −7% [95% CI, −15% to −3%]). Among the patients who required tracheal intubation, there was a statistically significant increase in the median time to tracheal intubation in the CPAP group (2.0 days [IQR, 1.0 to 4.0 days]) compared with the conventional oxygen therapy group (1.0 day [IQR, 0 to 4.0 days]) (median difference, 1.0 day [95% CI, 0.2 to 1.8 days]).
Meanwhile, adverse events occurred in 34.2% (130/380) of patients in the CPAP group, 20.6% (86/418) of patients in the HFNO group, and 13.9% (66/475) of patients in the conventional oxygen therapy group. Eight patients experienced serious adverse events (7 in the CPAP group and 1 in the conventional oxygen therapy group). Four of the serious adverse events were classified as probably or possibly linked to the trial intervention and all of these events occurred in the CPAP group.
“[The] decrease in the incidence of the primary outcome with CPAP was attributable to a significant decrease in the need for tracheal intubation. Neither HFNO nor CPAP reduced mortality compared with conventional oxygen therapy,” the authors wrote, noting that “one explanation for these discordant findings is differences in pathophysiology between COVID pneumonitis and other causes of acute respiratory failure.”
“Furthermore, in the RECOVERY-RS trial, some hospitals modified care pathways to deliver CPAP and HFNO outside an ICU, which may have influenced the clinical effectiveness of the interventions,” the authors added.