Restrictive Vs. Liberal Oxygen in Trauma

NCT05146700 | Completed Phase 4 DMC

• 3 other identifiers: 60112021-000556-19NNF20OC0063985
• Study Type: interventional
• Target: 1,508
• Locations: 3 countries
• Sites: 5

Brief Summary

Victims of trauma are often healthy individuals prior to the incident, but acquire numerous complications including sepsis and pulmonary complications and diminished quality of life after trauma. According to Advanced Trauma Life Support guidelines, all severely injured trauma patients should receive supplemental oxygen. The objective of TRAUMOX2 is to compare the effect of a restrictive versus liberal oxygen strategy the first eight hours following trauma on the incidence of 30-day mortality and/or major respiratory complications (pneumonia and acute respiratory distress syndrome) within 30 days (combined primary endpoint).

Conditions

Trauma; Oxygen Toxicity; Wounds and Injuries

Keywords

Trauma; Oxygen

Outcome Measures

Primary Outcomes (1)

• The incidence of 30-day mortality and/or major respiratory complications (pneumonia and acute respiratory distress syndrome) within 30 days (combined primary endpoint)

  The assessment of the major respiratory complications will be performed by at least two allocation blinded primary outcome assessors (specialists in anesthesiology, intensive care, emergency medicine or similar); blinding will be ensured by concealing all information indicative of the allocation prior to assessment

  Day 30 after enrollment

Secondary Outcomes (15)

• 30-day mortality

  Day 30 after enrollment

• 12-month mortality

  12 months after enrollment

• Major respiratory complications (pneumonia and acute respiratory distress syndrome) within 30 days

  Day 30 after enrollment

• Hospital length of stay

  From date of admission to discharge from the hospital, up to 12 months after enrollment

• ICU length of stay

  From date of admission to discharge from the ICU, up to 12 months after enrollment

Study Arms (2)

Restrictive oxygen

EXPERIMENTAL

\- Lowest oxygen delivery possible (≥21%) ensuring an SpO2 target = 94% either using no supplemental oxygen, a nasal cannula, a non-rebreather mask or manual/mechanical ventilation (intubated trial participants) and \- Only trial participants receiving an FiO2 = 0.21 can saturate \>94% Pre-oxygenation as usual prior to intubation is permitted

Drug: Restrictive oxygen

Liberal oxygen

ACTIVE COMPARATOR

\- 15 L O2/min flow for non-intubated trial participants in the pre-hospital phase, the trauma bay and during intrahospital transportation. In the operating room, intensive care unit, post-anesthesia care unit and ward the flow can be reduced to ≥12 L O2/min if the arterial oxygen saturation is ≥98% or \- FiO2 = 1.0 for intubated trial participants in the pre-hospital phase, the trauma bay and during intrahospital transportation. In the operating room, intensive care unit, post-anesthesia care unit and ward the FiO2 can be reduced to ≥0.6 if the arterial oxygen saturation is ≥98%

Drug: Liberal oxygen

Interventions

Restrictive oxygen DRUG

Lowest oxygen delivery possible (≥21%) ensuring an SpO2 target = 94%

Restrictive oxygen

Liberal oxygen DRUG

15 L O2/min flow for non-intubated trial participants or FiO2 = 1.0 for intubated trial participants in the initial phase; later in the operating room, intensive care unit, post-anesthesia care unit and ward, the flow/FiO2 can be reduced to ≥12 L O2/min or FiO2 ≥0.6 if the arterial oxygen saturation is ≥98%

Liberal oxygen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years, including fertile women
• Blunt or penetrating trauma mechanism
• Direct transfer from the scene of accident to one of the participating trauma centers
• Trauma team activation
• The enrolling physician must initially expect a hospital length of stay for 24 hours or longer

You may not qualify if:

• Patients in cardiac arrest before or on admission
• Patients with a suspicion of carbon monoxide intoxication
• Patients with no/minor injuries after secondary survey will be excluded if they are expected to be discharged \<24 hours

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• The Novo Nordic Foundation: collaborator

Study Sites (5)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Rigshospitalet, Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Erasmus MC, University Medical Center Rotterdam

Rotterdam, Rotterdam, 3000, Netherlands

Location

Inselspital University Hospital Bern

Bern, 3010, Switzerland

Location

Related Publications (3)

• Arleth T, Baekgaard J, Siersma V, Creutzburg A, Dinesen F, Rosenkrantz O, Heiberg J, Isbye D, Mikkelsen S, Hansen PM, Zwisler ST, Darling S, Petersen LB, Morkeberg MCR, Andersen M, Fenger-Eriksen C, Bach PT, Van Vledder MG, Van Lieshout EMM, Ottenhof NA, Maissan IM, Den Hartog D, Hautz WE, Jakob DA, Iten M, Haenggi M, Albrecht R, Hinkelbein J, Klimek M, Rasmussen LS, Steinmetz J; TRAUMOX2 Trial Group. Early Restrictive vs Liberal Oxygen for Trauma Patients: The TRAUMOX2 Randomized Clinical Trial. JAMA. 2025 Feb 11;333(6):479-489. doi: 10.1001/jama.2024.25786.

  PMID: 39657224 DERIVED

• Arleth T, Baekgaard J, Siersma V, Klimek M, Hinkelbein J, Rasmussen LS, Steinmetz J; TRAUMOX2 Study Group. Comparing restrictive versus liberal oxygen strategies for trauma patients: The TRAUMOX2 trial-Statistical analysis plan. Acta Anaesthesiol Scand. 2023 Jul;67(6):829-838. doi: 10.1111/aas.14230. Epub 2023 Mar 28.

  PMID: 36906804 DERIVED

• Baekgaard J, Arleth T, Siersma V, Hinkelbein J, Yucetepe S, Klimek M, van Vledder MG, Van Lieshout EMM, Mikkelsen S, Zwisler ST, Andersen M, Fenger-Eriksen C, Isbye DL, Rasmussen LS, Steinmetz J. Comparing restrictive versus liberal oxygen strategies for trauma patients - the TRAUMOX2 trial: protocol for a randomised clinical trial. BMJ Open. 2022 Nov 7;12(11):e064047. doi: 10.1136/bmjopen-2022-064047.

  PMID: 36344005 DERIVED

Related Links

• The official study website of TRAUMOX2

MeSH Terms

Conditions

Wounds and Injuries

Study Officials

• Jacob Steinmetz, MD, PhD

  Consultant

  STUDY DIRECTOR

• Tobias Arleth, MD

  Research assistent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Open-label, primary outcome assessor- and analyst-blinded, randomized, controlled clinical trial with regards to treatment: treating staff will be aware of the trial participants' randomization group. While including patients for the study, the research team and treating staff will be aware of the trial participants' oxygen allocation strategy. However, at least two allocation blinded primary outcome assessors (specialists in anesthesiology, intensive care, emergency medicine or similar) will be appointed at each center to assess in-hospital major lung complications (pneumonia and acute respiratory distress syndrome). Blinding will be ensured by concealing all information indicative of the allocation prior to assessment. The statistician and manuscript writers will be blinded towards the allocation of treatment once the trial ends when data is being analysed and the manuscript is drafted.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: Trial participants are randomized pre-hospital or in the trauma bay to a restrictive or liberal oxygen treatment for eight hours. Experimental (restrictive oxygen): The restrictive group will receive the lowest dosage of oxygen (≥21%) ensuring an SpO2 target = 94% Active comparator (liberal oxygen): The liberal group will receive a flow of 15 L O2/min for non-intubated trial participants or an FiO2 = 1.0 for intubated trial participants in the pre-hospital phase, the trauma bay and during intrahospital transportation; later in the operating room (OR), intensive care unit (ICU), post-anesthesia care unit (PACU) and ward, the flow/FiO2 can be reduced to ≥12 L O2/min or FiO2 ≥0.6 if the arterial oxygen saturation (SpO2) is ≥98%

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: December 7, 2021
• Study Start: December 10, 2021
• Primary Completion: October 12, 2023
• Study Completion: October 12, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

DK (3); NL (1); CH (1)