High-flow nasal oxygen noninferior to noninvasive ventilation in acute respiratory failure

Key takeaways:

• Researchers split the total cohort into five groups.
• All groups minus immunocompromised patients with hypoxemia showed high-flow nasal oxygen noninferiority in the occurrence of intubation/death at 7 days.

When assessing intubation/death at 7 days in hospitalized adults with acute respiratory failure, high-flow nasal oxygen was generally noninferior to noninvasive ventilation, according to results published inJAMA.

“The RENOVATE trial shows that high-flow nasal oxygen (HFNO) may be the first respiratory support choice for most groups of patients with acute respiratory failure, because it is better tolerated and more comfortable than noninvasive ventilation (NIV), with noninferior rates of need of intubation or death within 7 days,” Alexandre Biasi Cavalcanti, MD, PhD, director of education and research at Hcor Research Institute in São Paulo, told Healio.

In the noninferiority, randomized, multicenter RENOVATE clinical trial, Cavalcanti, Israel S. Maia, MD, PhD, of Hcor Research Institute, Leticia Kawano-Dourado, MD, PhD, of Hcor Research Institute, and colleagues evaluated 1,766 adults (mean age, 63.7 years; 40% women) hospitalized with acute respiratory failure receiving either HFNO (n = 883) or NIV (n = 883) to compare proportions of patients who underwent endotracheal intubation/died at the 7-day mark between the two respiratory support options.

If a posterior probability reached at least 0.992 for an odds ratio below 1.55, noninferiority was observed based on this study’s definition.

Researchers split the total cohort into five groups. The hypoxemic COVID-19 group had the most patients at 882, followed by the nonimmunocompromised with hypoxemia group (n = 485), the acute cardiogenic pulmonary edema (ACPE) group (n = 272), the COPD exacerbation with respiratory acidosis group (n = 77) and the immunocompromised with hypoxemia group (n = 50).

“RENOVATE offered estimates of treatment effect for five different groups of patients with acute respiratory failure, instead of a single estimate of treatment effect as obtained in conventional clinical trials,” Cavalcanti told Healio. “This approach might be adopted in future studies to provide information specific to different patient groups — that is, it is an effort towards a more personalized care for critically ill patients.”

When considering the entire study population at day 7, a similar proportion of patients receiving HFNO and patients receiving NIV experienced intubation or death (39% vs. 38.1%), according to researchers.

Moving into the five subgroups, researchers found results via a Bayesian hierarchical model with dynamic borrowing across the groups.

The only group that did not exhibit noninferiority of HFNO vs. NIV was the one that included immunocompromised patients with hypoxemia (OR = 1.07; 95% credible interval [CrI], 0.81-1.39; noninferiority posterior probability [NPP] = 0.989). Within this group, the proportion of patients who experienced intubation or death was higher among those receiving HFNO vs. NIV (57.1% vs. 36.4%).

Notably, researchers highlighted an important factor to consider when interpreting the results from this group.

“The first group (immunocompromised with hypoxemia) was stopped early for futility in the first interim analysis, with only 50 patients,” Cavalcanti told Healio. “We believe that the threshold for stopping for futility might have been set too high (a posterior probability of noninferiority lower than 30%), that is, stopping would have been common even if the true primary outcome rates are the same in the HFNO and NIV arms in that group.

“That is, it is possible that future studies might reach a conclusion of noninferiority of HFNO in that group,” Cavalcanti continued.

The remaining four groups showed HFNO noninferiority when assessing the occurrence of intubation or death at 7 days:

• hypoxemic COVID-19 (OR = 1.13; 95% CrI, 0.94-1.38; NPP = 0.997);
• nonimmunocompromised with hypoxemia (OR = 1.02; 95% CrI, 0.81-1.26; NPP = 0.999);
• ACPE (OR = 0.97; 95% CrI, 0.73-1.23; NPP = 0.997); and
• COPD exacerbation with respiratory acidosis (OR = 1.05; 95% CrI, 0.79-1.36; NPP = 0.992).

“We were happy to find that noninferiority of HFNO vs. NIV was the conclusion for most groups of patients with acute respiratory failure,” Cavalcanti told Healio.

In three of these groups, the proportion of patients that experienced intubation or death at 7 days did not differ by more than 5% when comparing HFNO and NIV. The group with more varying proportions was those with ACPE, as a higher proportion of patients receiving NIV vs. HFNO experienced this outcome (21.3% vs. 10.3%).

After removing dynamic borrowing across the five groups, researchers observed three groups with “qualitatively different results”: the COPD exacerbation with respiratory acidosis group, the immunocompromised with hypoxemia group and the ACPE group.

“The COPD group was small, and the results of the primary analysis (with dynamic borrowing) are discrepant from those of a post hoc sensitivity analysis without borrowing,” Cavalcanti told Healio. “Results in the analysis without borrowing were not compatible with noninferiority.”

In terms of safety, 9.4% of those receiving HFNO reported a serious adverse event, and this was close to the 9.9% of those receiving NIV who reported this type of event.

“Future trials assessing the effectiveness of HFNO vs. NIV are needed for immunocompromised patients with hypoxemia and COPD,” Cavalcanti told Healio.

For more information:

Alexandre Biasi Cavalcanti, MD, PhD, can be reached at abiasi@hcor.com.br.

Israel S. Maia, MD, PhD, can be reached at israelsmaia@hcor.com.br.

Leticia Kawano-Dourado, MD, PhD, can be reached at ldourado@hcor.com.br.