CAVIARDS Trial

The target sample size is 740 patients total, with 370 patients in each of the two substudies. The statistical analysis plan assumes the intervention can reduce day-60 mortality by an absolute 15%, powering the trial at 80%. The trial was originally designed for COVID-19 ARDS and was modified to a basket design on 8 November 2023 because of the major decrease in COVID-19 incidence. There is no futility stopping rule because early futility stopping could increase type II false-negative error. Analyses follow the intention-to-treat principle, including all randomised patients regardless of protocol compliance. The primary outcome is all-cause mortality within 60 days of randomisation. CAVIARDS is a multicentre, open-label, phase III randomised controlled basket trial evaluating whether a physiology-based ventilation strategy improves outcomes in adults with moderate-to-severe ARDS. The trial is being conducted in 33 intensive care units across eight countries: Argentina, Canada, Chile, France, Italy, Spain, the Netherlands, and the United States.