Research Summary

Can High-Flow Nasal Oxygen Match Noninvasive Ventilation in Acute Respiratory Failure?

Anthony Calabro, MA

Key Highlights

  • High-flow nasal oxygen (HFNO) was noninferior to noninvasive ventilation (NIV) for the composite outcome of intubation or death at 7 days in 4 of 5 patient groups.
  • In the immunocompromised with hypoxemia group, enrollment was stopped for futility, and noninferiority was not established.
  • Serious adverse event rates were similar between HFNO and NIV (9.4% vs 9.9%).
  • Findings were sensitive to analytic methods, suggesting caution in chronic obstructive pulmonary disease and cardiogenic pulmonary edema subgroups.

In a large, multicenter randomized trial, high-flow nasal oxygen (HFNO) was shown to be noninferior to noninvasive ventilation (NIV) for preventing endotracheal intubation or death within 7 days among patients with acute respiratory failure across most subgroups studied.

Acute respiratory failure (ARF) is a common and critical condition with multiple causes, including hypoxemia, chronic obstructive pulmonary disease (COPD) exacerbations, cardiogenic pulmonary edema, and COVID-19. Clinicians frequently use either NIV or HFNO, but evidence directly comparing these modalities has been limited. While guidelines support NIV in COPD exacerbations and cardiogenic pulmonary edema, those recommendations were based on comparisons with low-flow oxygen rather than HFNO. Meanwhile, HFNO has gained favor for hypoxemic ARF, including in patients with COVID-19, because of its physiological and comfort advantages. Despite this, questions remained regarding whether HFNO could match NIV in preventing intubation or early mortality.

The RENOVATE trial was a multicenter, adaptive, noninferiority randomized clinical trial conducted at 33 hospitals in Brazil. Adults with ARF were stratified into five groups: nonimmunocompromised with hypoxemia, immunocompromised with hypoxemia, COPD exacerbation with respiratory acidosis, acute cardiogenic pulmonary edema, and hypoxemic COVID-19. A total of 1766 patients were randomized to receive HFNO (n = 883) or NIV (n = 883). The primary outcome was the composite of intubation or death within 7 days, assessed with a Bayesian hierarchical model incorporating dynamic borrowing across groups. Noninferiority was prespecified as a posterior probability of 0.992 or greater for an OR of less than 1.55.

Overall, the primary outcome occurred in 39% of the HFNO group and 38% of the NIV group. Noninferiority was demonstrated in four patient groups. Among patients who are immunocompromised with hypoxemia, the composite outcome occurred in 32.5% with HFNO vs 33.1% with NIV (OR, 1.02; noninferiority posterior probability [NPP], 0.999). In acute cardiogenic pulmonary edema, events occurred in 10.3% with HFNO vs 21.3% with NIV (OR, 0.97; NPP, 0.997). In hypoxemic COVID-19, the event rate was 51.3% vs 47.0% (OR, 1.13; NPP, 0.997). In COPD exacerbations with acidosis, rates were 28.6% vs 26.2% (OR, 1.05; NPP, 0.992). However, in the immunocompromised hypoxemia group, the composite outcome occurred more frequently in the HFNO group (57.1% vs 36.4%), and enrollment was stopped for futility (NPP, 0.989). Secondary outcomes, including 28- and 90-day mortality, did not differ significantly between groups. Comfort was superior with HFNO.

Despite the robust design, the trial had limitations. The immunocompromised subgroup was small, limiting power, and the adaptive borrowing approach may have influenced subgroup estimates. Post hoc analyses without borrowing suggested possible discrepancies in COPD and cardiogenic pulmonary edema groups. Furthermore, the trial excluded patients needing urgent intubation or with more severe disease, limiting generalizability to the sickest patients.

“Compared with noninvasive ventilation, high-flow nasal oxygen met prespecified criteria for noninferiority for the primary outcome of endotracheal intubation or death within 7 days in four of the five patient groups with acute respiratory failure,” the authors concluded. “However, the small sample sizes in some patient groups and the sensitivity of the findings to the choice of analysis model suggests the need for further study in patients with COPD, immunocompromised patients, and patients with acute cardiogenic pulmonary edema.”

Reference
RENOVATE Investigators and the BRICNet Authors, Maia IS, Kawano-Dourado L, et al. High-flow nasal oxygen vs noninvasive ventilation in patients with acute respiratory failure: the RENOVATE randomized clinical trial. JAMA. 2025;333(10):875-890. doi:10.1001/jama.2024.26244