Stability of ARDS subphenotypes over time in two randomised controlled trials

Rationale Two distinct acute respiratory distress syndrome (ARDS) subphenotypes have been identified using data obtained at time of enrolment in clinical trials; it remains unknown if these subphenotypes are durable over time. Objective To determine the stability of ARDS subphenotypes over time. Methods Secondary analysis of data from two randomised controlled trials in ARDS, the ARMA trial of lung protective ventilation (n=473; patients randomised to low tidal volumes only) and the ALVEOLI trial of low versus high positive end-expiratory pressure (n=549). Latent class analysis (LCA) and latent transition analysis (LTA) were applied to data from day 0 and day 3, independent of clinical outcomes. Measurements and main results In ALVEOLI, LCA indicated strong evidence of two ARDS latent classes at days 0 and 3; in ARMA, evidence of two classes was stronger at day 0 than at day 3. The clinical and biological features of these two classes were similar to those in our prior work and were largely stable over time, though class 2 demonstrated evidence of progressive organ failures by day 3, compared with class 1. In both LCA and LTA models, the majority of patients (>94%) stayed in the same class from day 0 to day 3. Clinical outcomes were statistically significantly worse in class 2 than class 1 and were more strongly associated with day 3 class assignment. Conclusions ARDS subphenotypes are largely stable over the first 3 days of enrolment in two ARDS Network trials, suggesting that subphenotype identification may be feasible in the context of clinical trials.