Background: Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen prior to the procedure (preoxygenation) decreases the risk of hypoxemia during intubation. Research Question: Whether preoxygenation with noninvasive ventilation prevents hypoxemia during tracheal intubation of critically ill adults, compared to preoxygenation with oxygen mask, remains uncertain. Study Design and Methods: The PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) is a prospective, multicenter, non-blinded randomized comparative effectiveness trial being conducted in 7 emergency departments and 17 intensive care units across the United States. The trial compares preoxygenation with noninvasive ventilation versus oxygen mask among 1300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask prior to induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 minutes after intubation. Enrollment began on 10 March 2022 and is expected to conclude in 2023. Interpretation: The PREOXI trial will provide important data on the effectiveness of noninvasive ventilation and oxygen mask preoxygenation for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan prior to the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial. Clinical trial registration number: NCT05267652

Kevin W. Gibbs MD reports financial support and travel were provided by US Department of Defense. Adit. A. Ginde MD MPH reports financial support was provided by US Department of Defense. Matthew E. Prekker MD MPH reports financial support was provided by US Department of Defense. Kevin P. Seitz MD MSc reports financial support was provided by National Heart Lung and Blood Institute. Susan B. Stempek PA MBA reports financial support was provided by American College of Chest Physicians. Akram Khan MD reports financial support was provided by United Therapeutics Corporation. Akram Khan MD reports financial support was provided by 4D Medicine Ltd. Akram Khan MD reports financial support was provided by Regeneron Pharmaceuticals Inc. Akram Khan MD reports financial support was provided by Roche. Akram Khan MD reports financial support was provided by Dompe pharmaceutical. Jessica A. Palakshappa MD MS reports financial support was provided by National Institute on Aging. Joanne M. Wozniak PA MS reports was provided by American College of Chest Physicians. Matthew C. Exline MD, MPH reports financial support was provided by Abbott Laboratories. Derek W. Russell MD reports financial support was provided by National Heart Lung and Blood Institute. Shekar Ghamande MD reports financial support was provided by US Department of Defense. Ari Moskowitz MD MPH reports financial support was provided by National Heart Lung and Blood Institute. Jill Bastman BSN reports financial support was provided by US Department of Defense. Micah T. Long MD reports financial support was provided by pocket cards. Steven G. Schauer DO MS reports was provided by US Department of Defense. David Janz MD MSc reports financial support was provided by US Department of Defense. Matthew W. Semler MD MSc reports financial support was provided by US Department of Defense. Matthew W. Semler MD MSc reports financial support was provided by National Heart Lung and Blood Institute. Jonathan D. Casey MD MSc reports was provided by US Department of Defense. Jonathan D. Casey MD MSc reports was provided by National Heart Lung and Blood Institute. Jonathan D. Casey MD MSc reports travel was provided by Fisher & Paykel Healthcare Inc. Todd W Rice MD MSc reports a relationship with Cumberland Pharmaceuticals Inc that includes: consulting or advisory and equity or stocks. Derek W. Russell MD reports a relationship with Achieve Life Science Inc that includes: equity or stocks. Matthew W. Semler MD MSc reports a relationship with Baxter International Inc that includes: consulting or advisory.

NCT05267652

The research was funded primarily by the Department of Defense, Defense Health Agency, J9 Office, RESTORAL program. Kevin P. Seitz was supported in part by the NIH (T32HL087738). Jessica A. Palakshappa was supported in part by the NIA (K23AG073529) Matthew W. Semler was supported in part by the NHLBI (K23HL143053). Jonathan D. Casey was supported in part by the NHLBI (K23HL153584). Derek Russell was supported in part by the NHLBI (K08HL148514-01A1). Data collection utilized the Research Electronic Data Capture (REDCap) tool developed and maintained with Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding institutions had no role in (1) conception, design, or conduct of the study, (2) collection, management, analysis, interpretation, or presentation of the data. The views expressed are those of the author and do not reflect the official views or policy of the Department of Defense, its Components. The authors do not have any financial interest in the companies whose materials are discussed in this publication, and no federal endorsement of the companies and materials is intended.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The trial was approved with waiver of informed consent by the Single Institutional Review Board at Vanderbilt University Medical Center with secondary concurrence by the Department of Defense Office of Human Research Protections.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors