Protocol and statistical analysis plan for the Pragmatic Investigation of optimaL Oxygen Targets (PILOT) clinical trial.

Abstract

Mechanical ventilation of intensive care unit (ICU) patients universally involves titration of the fraction of inspired oxygen to maintain arterial oxygen saturation (SpO₂). However, the optimal SpO₂ target remains unknown. The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is a prospective, unblinded, pragmatic, cluster-crossover trial being conducted in the emergency department (ED) and medical ICU at Vanderbilt University Medical Center in Nashville, Tennessee, USA. PILOT compares use of a lower SpO₂ target (target 90% and goal range: 88%-92%), an intermediate SpO₂ target (target 94% and goal range: 92%-96%) and a higher SpO₂ target (target 98% and goal range: 96%-100%). The study units are assigned to a single SpO₂ target (cluster-level allocation) for each 2-month study block, and the assigned SpO₂ target switches every 2 months in a randomly generated sequence (cluster-level crossover). The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of invasive mechanical ventilation through 28 days after enrolment. The trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. The trial protocol was registered with ClinicalTrials.gov on 25 May 2018 prior to initiation of patient enrolment (ClinicalTrials.gov identifier: NCT03537937).