Restrictive Vs. Liberal Oxygen in Trauma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

1508 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-10

Study Completion Date

2024-10-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Hypoxemia in the First 24 Hours After Trauma - an Observational Study

NCT06256692

Trauma Trauma Injury Hypoxemia +2 more

COMPLETED

Management of Moderately Hypoxemic Thoracic Trauma

NCT03997630

Chest Trauma High Flow Oxygenation

ACTIVE_NOT_RECRUITING NA

Evaluation of Non-Invasive Hemoglobin in Trauma Patients

NCT03123328

Trauma

COMPLETED NA

Pre-hospital Hypoxemia in Trauma Patients

NCT01074983

Trauma

COMPLETED

Supplemental Oxygen in Hypovolemia

NCT05150418

Hypovolemia Hyperoxia

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

In trauma resuscitation, supplemental oxygen is often administered both to treat and prevent hypoxemia as recommended both by the Advanced Trauma Life Support (ATLS) manual and the Pre-hospital Trauma Life Support (PHTLS) manual. Oxygen is administered in many other situations too, sometimes in a non-consistent manner and very often without even being prescribed. In a recent systematic review, our group found the evidence both for and against the use of supplemental oxygen in the trauma population to be extremely sparse. However, a recent systematic review and meta-analysis comparing liberal versus restrictive oxygen strategy for a broad mix of acutely ill medical and surgical patients found an association between liberal oxygen administration and increased mortality. Of note, only one small study on trauma patients (patients with traumatic brain injury), which did not report mortality data, was included. Conversely, this study showed that degree of disability was significantly reduced at six months in the group receiving liberal compared to restrictive oxygen.

In mechanically ventilated patients hyperoxemia is commonly observed (16-50%), and hyperoxemia is a common finding in trauma patients in general. In addition to mortality, hyperoxemia has been associated with major pulmonary complications in the Intensive Care Unit (ICU) as well as in surgical patients. For example, a recent retrospective study found hyperoxemia to be an independent risk factor for ventilator associated pneumonia (VAP). Nevertheless, a highly debated recommendation from the World Health Organisation strongly recommends that adult patients undergoing general anesthesia for surgical procedures receive a fraction of inspired oxygen (FiO2) of 80% intraoperatively as well as in the immediate postoperative period for two to six hours to reduce the risk of surgical site infection. Furthermore, a study on 152,000 mechanically ventilated patients found no association between hyperoxia and mortality during the first 24 hours in the ICU, and another study on 14,000 mixed ICU patients found that a partial arterial oxygen pressure (PaO2) of approximately 18 kPa resulted in the lowest mortality. Finally, a recent study randomized 2928 ICU patients to either low or high oxygenation (defined as 8 vs 12 kPa) for a maximum of 90 days and found no difference in mortality. Therefore, whether the trauma population could benefit from a more restrictive supplemental oxygen approach than recommended by current international guidelines presents a large and important knowledge gap.

In a recent pilot randomized clinical trial (TRAUMOX1, ClinicalTrials.gov Registration number: NCT03491644), we compared a restrictive and a liberal oxygen strategy for 24 hours after trauma (N = 41) and found maintenance of normoxemia following trauma using a restrictive oxygen strategy to be feasible. TRAUMOX1 served as the basis for this larger trial. We experienced 24 hours to be slightly excessive to represent only the acute phase post trauma for which reason we have shortened the time-period to eight hours in TRAUMOX2. Furthermore, we found that several physicians had important concerns with the high dosage of oxygen in the liberal arm for which reason the concentration will be reduced. Finally, we did not randomize trauma patients in the pre-hospital phase, but instead on arrival at the trauma bay (median \[interquartile range (IQR)\] time to randomization: 7 \[4-10\] minutes, median \[IQR\] time from trauma to trauma bay arrival: 51 \[29.0-67.5\] minutes). To limit this inconsistent exposure to oxygen in the pre-hospital phase prior to inclusion we will initiate the intervention in the pre-hospital phase where possible in TRAUMOX2.

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).

We hypothesize that a restrictive compared to a liberal oxygen strategy for the initial eight hours after trauma will result in a lower rate of 30-day mortality and/or major respiratory complications (pneumonia and acute respiratory distress syndrome) within 30 days (combined primary endpoint).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Trauma Oxygen Toxicity Wounds and Injuries

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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%

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Restrictive oxygen

\- 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

Group Type EXPERIMENTAL

Restrictive oxygen

Intervention Type DRUG

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

Liberal oxygen

\- 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%

Group Type ACTIVE_COMPARATOR

Liberal oxygen

Intervention Type 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%

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Restrictive oxygen

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

Intervention Type DRUG

Liberal oxygen

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%

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No