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

Matthew W Semler, Jonathan D Casey, Bradley D Lloyd, Pamela G Hastings, Margaret Hays, Megan Roth, Joanna Stollings, John Brems, Kevin George Buell, Li Wang, Christopher J Lindsell, Robert E Freundlich, Jonathan P Wanderer, Gordon R Bernard, Wesley H Self, Todd W Rice, PILOT Investigators and the Pragmatic Critical Care Research Group, Robert E Freundlich, Jonathan P Wanderer, Christopher J Lindsell, Jin H Han, Wesley H Self, John H Brems, Kevin G Buell, Sneha Patel, Joanna L Stollings, Gordon R Bernard, Jonathan D Casey, Christina Cleveland, Margaret A Hays, Luis E Huerta, Karen Jackson, Todd W Rice, Megan Roth, Matthew W Semler, Pamela G Hastings, Bradley D Lloyd, Roger K Richardson, J Craig Rooks, Matthew W Semler, Jonathan D Casey, Bradley D Lloyd, Pamela G Hastings, Margaret Hays, Megan Roth, Joanna Stollings, John Brems, Kevin George Buell, Li Wang, Christopher J Lindsell, Robert E Freundlich, Jonathan P Wanderer, Gordon R Bernard, Wesley H Self, Todd W Rice, PILOT Investigators and the Pragmatic Critical Care Research Group, Robert E Freundlich, Jonathan P Wanderer, Christopher J Lindsell, Jin H Han, Wesley H Self, John H Brems, Kevin G Buell, Sneha Patel, Joanna L Stollings, Gordon R Bernard, Jonathan D Casey, Christina Cleveland, Margaret A Hays, Luis E Huerta, Karen Jackson, Todd W Rice, Megan Roth, Matthew W Semler, Pamela G Hastings, Bradley D Lloyd, Roger K Richardson, J Craig Rooks

Abstract

Introduction: 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.

Methods and analysis: 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.

Ethics and dissemination: 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.

Trial registration number: The trial protocol was registered with ClinicalTrials.gov on 25 May 2018 prior to initiation of patient enrolment (ClinicalTrials.gov identifier: NCT03537937).

Keywords: accident & emergency medicine; adult intensive & critical care; clinical trials.

Conflict of interest statement

Competing interests: All authors completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. RF reported receiving grant funding and consulting fees from Medtronic and stock from 3M outside the current work. TWR reported receiving consulting fees from Cumberland Pharmaceuticals outside the current work. The authors declared no potential conflicts of interest with the current work.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Standard Protocol Items: Recommendations for Interventional Trials checklist. Enrolment, interventions and assessments. FiO2, fraction of inspired oxygen; SpO2, arterial oxygen saturation.
Figure 2
Figure 2
Group assignment during the trial. For each of the 18 2-month study periods, the study intensive care unit is randomly assigned to a higher, intermediate or lower SpO2 target. in this figure, The letters ‘A’, ‘B’ and ‘C’ each correspond to one of the three possible SpO2 targets, the allocation sequence of which remains concealed until the start of each 2-month study period. The study did not enrol in April and May of 2020 due to disruptions in research and clinical care from the COVID-19 pandemic. As a result, March and June of 2020 represent a single 2-month block assigned to one SpO2 target. SpO2, arterial oxygen saturation.

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