Clinical Trial Results:
Comparing Restrictive vs. Liberal Oxygen Strategies for Trauma Patients: The TRAUMOX2 Trial
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Summary
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EudraCT number |
2021-000556-19 |
Trial protocol |
DK |
Global end of trial date |
12 Oct 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Oct 2025
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First version publication date |
23 Oct 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
6011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05146700 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Rigshospitalet, Denmark
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Sponsor organisation address |
Inge Lehmanns Vej 6, Copenhagen, Denmark, 2100
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Public contact |
Jacob Steinmetz, Rigshospitalet, Denmark, Department of Anaesthesiology, Centre of Head and Orthopaedics, +45 35458434, jacob.steinmetz@regionh.dk
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Scientific contact |
Jacob Steinmetz, Rigshospitalet, Denmark, Department of Anaesthesiology, Centre of Head and Orthopaedics, +45 35458434, jacob.steinmetz@regionh.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Jul 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Feb 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Oct 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The objective of this trial, TRAUMOX2, will be to compare the effect of a restrictive versus liberal oxygen strategy the first eight hours after trauma on the incidence of 30-day mortality and/or major respiratory complications (pneumonia and acute respiratory distress syndrome) within 30 days (combined endpoint).
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Protection of trial subjects |
No additional protection besides standard care according to local practice.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Dec 2021
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Scientific research | ||
Long term follow-up duration |
1 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 185
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Country: Number of subjects enrolled |
Denmark: 1226
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Country: Number of subjects enrolled |
Switzerland: 97
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Worldwide total number of subjects |
1508
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EEA total number of subjects |
1411
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1122
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From 65 to 84 years |
334
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85 years and over |
52
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Recruitment
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Recruitment details |
Active recruitment from December 7, 2021, to September 12, 2023. 30-day follow-up ended October 12, 2023. 1-year follow-up ended October 12, 2024. Recruitment across 5 major traumacenters and 15 prehospital bases in Denmark, The Netherlands, and Switzerland. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Inclusion Criteria: Patients aged ≥18; Blunt or penetrating trauma; Direct transfer to one of the participating trauma centers; Trauma team activation; Expected hospital length of stay for 24 hours or longer Exclusion Criteria: Patients with cardiac arrest prior to randomisation; Carbon monoxide intoxication; No/minor injuries after secondary surv | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Blinding implementation details |
Open-label. Primary outcome was assessor blinded.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Restrictive oxygen | |||||||||||||||||||||
Arm description |
- 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 | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use, Nasal use
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Dosage and administration details |
- 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
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Arm title
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Liberal oxygen | |||||||||||||||||||||
Arm description |
- 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% | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use, Nasal use
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Dosage and administration details |
- 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%
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Baseline characteristics reporting groups
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Reporting group title |
Restrictive oxygen
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Reporting group description |
- 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liberal oxygen
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Reporting group description |
- 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% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Restrictive oxygen
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Reporting group description |
- 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 | ||
Reporting group title |
Liberal oxygen
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Reporting group description |
- 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% | ||
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End point title |
Death and/or major respiratory complications | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
30-day outcome.
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Statistical analysis title |
Death and/or major respiratory complications | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
1457
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.01
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.75 | |||||||||
upper limit |
1.37 | |||||||||
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End point title |
Death | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30-day
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Statistical analysis title |
Death | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
1457
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.28
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.85 | |||||||||
upper limit |
1.92 | |||||||||
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End point title |
Major respiratory complications | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30-day outcome
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Statistical analysis title |
Major respiratory complications | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
1457
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.84
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.59 | |||||||||
upper limit |
1.19 | |||||||||
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End point title |
Hypoxemic episode(s) | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
During 8-hour intervention.
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Statistical analysis title |
Hypoxemic episodes | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
1474
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.67
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
1.02 | |||||||||
upper limit |
2.7 | |||||||||
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End point title |
ICU readmission | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
During the initial hospital admission (not at hospital readmission).
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Statistical analysis title |
ICU readmission | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
720
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.59
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.26 | |||||||||
upper limit |
1.37 | |||||||||
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End point title |
Sepsis | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
During the initial hospital admission (not at hospital readmission).
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Statistical analysis title |
Sepsis during hospital admission | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
1463
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.55
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.3 | |||||||||
upper limit |
1.02 | |||||||||
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End point title |
Surgical site infection | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Within 30 days after enrollment.
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Statistical analysis title |
Surgical site infections | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
1460
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.5
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.25 | |||||||||
upper limit |
0.99 | |||||||||
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End point title |
Pneumonia post discharge | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Within 30 days after enrollment.
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Statistical analysis title |
Pneumonia post-discharge | |||||||||
Comparison groups |
Restrictive oxygen v Liberal oxygen
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Number of subjects included in analysis |
1260
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
Method |
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Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.06
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.6 | |||||||||
upper limit |
1.85 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
To monitor events, a TRAUMOX2 investigator assessed the trial participant’s medical record:
- Once within the first 24 hours after inclusion
- Every third day until discharge (maximum of 30 days)
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Adverse event reporting additional description |
The local investigators at each centre is responsible for recording the different types of events. All events were assessed for correlation between an event and trial medicine using this event policy:
1: Unrelated
2: Possible related
3: Probably related
4: Related
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
0
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Reporting groups
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Reporting group title |
Restrictive oxygen
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Reporting group description |
- 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liberal oxygen
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Reporting group description |
- 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% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/39657224 |
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