Heterogeneous Treatment Effects of High-Frequency Oscillatory Ventilation for Acute Respiratory Distress Syndrome: A Post Hoc Analysis of the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) Trial

Objectives: We sought to evaluate whether different subgroups of adults with acute respiratory distress syndrome (ARDS) respond differently to high-frequency oscillatory ventilation (HFOV).

Design: The Oscillation for ARDS Treated Early (OSCILLATE) trial was a randomized controlled trial of HFOV vs. conventional ventilation that found an increased risk of in-hospital mortality (primary outcome) with HFOV. In a post hoc analysis, we applied three different approaches to evaluate heterogeneity of treatment effect for in-hospital mortality: 1) subgroup analyses based on baseline Pao₂:Fio₂ ratio and oxygenation index (OI); 2) a risk-based approach using a multivariable outcome prediction model; and 3) a clustering approach via multivariable latent class analysis. We used multivariable logistic regression models to assess for interaction.

Setting: Thirty-nine ICUs, five countries.

Subjects: Five hundred forty-eight adults with moderate to severe ARDS.

Interventions: HFOV vs. conventional mechanical ventilation with low tidal volume and higher positive end-expiratory pressure.

Measurements and main results: The effect of HFOV on in-hospital mortality was consistent across categories of Pao₂:Fio₂ ratio (adjusted odds ratio [aOR], 2.04; 95% CI, 1.32-3.17 and aOR, 1.16; 95% CI, 0.49-2.75 for groups with Pao₂:Fio₂ above or equal to 80, vs. below 80, respectively; interaction p = 0.23) and OI (aOR, 1.78; 95% CI, 0.67-4.70; aOR, 3.19; 95% CI, 1.44-7.09; aOR, 1.73; 95% CI, 0.82-3.65; and aOR, 1.33; 95% CI, 0.61-2.90 for quartiles of baseline OI, respectively; interaction p = 0.44). Point estimates for the effect of HFOV were consistent across risk categories (aOR, 2.44; 95% CI, 0.40-14.83; aOR, 1.69; 95% CI, 0.75-3.85; and aOR, 2.10; 95% CI, 0.59-7.54 for the lowest, moderate, and highest risk categories, respectively; interaction p = 0.32). Using a clustering approach, point estimates for HFOV were also consistent (cluster 1: aOR, 1.85; 95% CI, 1.15-3.00 and cluster 2: aOR, 1.75; 95% CI, 0.91-3.38; interaction p = 0.75).

Conclusions: We did not identify heterogeneity in the effect of HFOV across different subgroups of patients with ARDS.