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.

Abstract

We sought to evaluate whether different subgroups of adults with acute respiratory distress syndrome (ARDS) respond differently to high-frequency oscillatory ventilation (HFOV). 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. Thirty-nine ICUs, five countries. Five hundred forty-eight adults with moderate to severe ARDS. HFOV vs. conventional mechanical ventilation with low tidal volume and higher positive end-expiratory pressure. 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). We did not identify heterogeneity in the effect of HFOV across different subgroups of patients with ARDS.