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.