Clinical Trial Results:
Restrictive vs. Liberal Oxygen Therapy for Trauma patients. PILOT: The
TRAUMOX Trial
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Summary
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EudraCT number |
2017-004480-12 |
Trial protocol |
DK |
Global end of trial date |
24 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Nov 2019
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First version publication date |
01 Nov 2019
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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 |
2017-991
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03491644 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Rigshospitalet
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Sponsor organisation address |
Juliane Maries Vej, Copenhagen, Denmark,
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Public contact |
Rigshospitalet, Rigshospitalet, 0045 35451257, josefine.stokholm.baekgaard.01@regionh.dk
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Scientific contact |
Rigshospitalet, Rigshospitalet, 0045 35451257, josefine.stokholm.baekgaard.01@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 Oct 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Jun 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Jun 2018
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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 primary objective of this trial is to evaluate whether the maintenance of pragmatic normoxia, avoiding both hyperoxic and hypoxic phases, is feasible within the first 24 hours after trauma, as it may result in a reduction of 30-day mortality and major respiratory complications within 30 days (respiratory failure, pulmonary edema, and pneumonia).
We will conduct a pilot study, where 40 patients are randomized to 24 hours of:
A. Restrictive, but sufficient oxygen treatment: lowest oxygen delivery that obtains a saturation of ≥ 94%
B. Liberal oxygen treatment: 15 L/min oxygen flow initially/ FiO2 ≥0.8
A. within the low limits of standard of care and does not put patients at risk of receiving worse treatment.
B. as close as possible to the standard of care. As no precise guidelines on oxygen delivery for trauma patients within the first 24 hours exist, this will however inevitably vary in practice.
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Protection of trial subjects |
Hourly check-ups during intervention and detailed information including available contact persons 24/7.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Apr 2018
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
1 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Denmark: 41
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Worldwide total number of subjects |
41
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EEA total number of subjects |
41
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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) |
32
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From 65 to 84 years |
7
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85 years and over |
2
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Recruitment
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Recruitment details |
As soon as the trauma team was activated a study staff member assessed the patient for inclusion. All patients where considered temporarily without the ability to consent and therefore proxy consent was sought by a trial guardian. Randomisation was then performed, and the trauma team leader was informed of the allocation and initiated treatment. | |||||||||||||||
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Pre-assignment
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Screening details |
Between April 4th, 2018, and May 23rd, 2018, 146 patients were screened, and we randomly assigned 41 trauma patients to receive 24 hours of restrictive (n=21) or liberal (n=20) oxygen therapy. | |||||||||||||||
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Period 1
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Period 1 title |
Intervention (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||
Roles blinded |
Assessor [1] | |||||||||||||||
Blinding implementation details |
Outcome assessors were 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 |
The restrictive group (intervention) implied the lowest dosage of oxygen (>21%) that ensured an arterial oxyhemoglobin saturation (SpO2) target of 94% either using mechanical ventilation, a non-rebreather mask, a nasal cannula, or no supplementary oxygen. Supplemental oxygen was not given unless the SpO2 was below 94% and thus, only spontaneously breathing patients without supplementary oxygen could saturate above 94%. In case the SpO2 became unmeasurable, the intervention was interrupted, and standard (liberal) treatment was applied. | |||||||||||||||
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 |
Medicinal gas, compressed
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Routes of administration |
Nasal use, Oral use
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Dosage and administration details |
The restrictive group (intervention) implied the lowest dosage of oxygen (>21%) that ensured an arterial oxyhemoglobin saturation (SpO2) target of 94% either using mechanical ventilation, a non-rebreather mask, a nasal cannula, or no supplementary oxygen. Supplemental oxygen was not given unless the SpO2 was below 94% and thus, only spontaneously breathing patients without supplementary oxygen could saturate above 94%. In case the SpO2 became unmeasurable, the intervention was interrupted, and standard (liberal) treatment was applied. The liberal group (control) was designed to mimic current practice and guidelines. 1,2 Here, non-intubated patients received 15 l/min via a non-rebreather mask and intubated patients received a FiO2 of 1.0 in the trauma bay and during intra-hospital transportation. In the operating room, ICU, post-anaesthesia care unit and ward the FiO2 could be reduced to 0.8 if an arterial oxygen saturation ≥ 98% was obtained.
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Arm title
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Liberal oxygen treatment | |||||||||||||||
Arm description |
The liberal group (control) was designed to mimic current practice and guidelines. Here, non-intubated patients received 15 l/min via a non-rebreather mask and intubated patients received a FiO2 of 1.0 in the trauma bay and during intra-hospital transportation. In the operating room, ICU, post-anaesthesia care unit and ward the FiO2 could be reduced to 0.8 if an arterial oxygen saturation ≥ 98% was obtained. | |||||||||||||||
Arm type |
Designed to mimic current practice and guidelines. | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Single center, open-label randomized clinical trial with regards to treatment: treating staff was aware of the patient’s randomization group Primary outcome assessors were blinded to the patients’ randomization. |
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Baseline characteristics reporting groups
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Reporting group title |
Intervention (overall period)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Restrictive oxygen
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Reporting group description |
The restrictive group (intervention) implied the lowest dosage of oxygen (>21%) that ensured an arterial oxyhemoglobin saturation (SpO2) target of 94% either using mechanical ventilation, a non-rebreather mask, a nasal cannula, or no supplementary oxygen. Supplemental oxygen was not given unless the SpO2 was below 94% and thus, only spontaneously breathing patients without supplementary oxygen could saturate above 94%. In case the SpO2 became unmeasurable, the intervention was interrupted, and standard (liberal) treatment was applied. | ||
Reporting group title |
Liberal oxygen treatment
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Reporting group description |
The liberal group (control) was designed to mimic current practice and guidelines. Here, non-intubated patients received 15 l/min via a non-rebreather mask and intubated patients received a FiO2 of 1.0 in the trauma bay and during intra-hospital transportation. In the operating room, ICU, post-anaesthesia care unit and ward the FiO2 could be reduced to 0.8 if an arterial oxygen saturation ≥ 98% was obtained. | ||
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End point title |
Incidence of 30-day mortality and major pulmonary complications (combined endpoint) [1] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
30-days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see the attached table and the linked published article explaining the statistics. |
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Attachments |
Endpoints |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Major pulmonary complicatoin | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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| No statistical analyses for this end point | ||||||||||
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End point title |
Mortality | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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| No statistical analyses for this end point | ||||||||||
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End point title |
Desaturation (<90%) episodes | |||||||||
End point description |
There were seven episodes in four patients of desaturation (SpO2 below 90%) in the restrictive group (median 87% [87-89]) and one episode of SpO2 below 90% in the liberal group (saturation= 89%). Of note, five of the seven cases of SpO2 below 89% occurred in two patients; one patient who had just been extubated and another patient who went into cardiac arrest.
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End point type |
Secondary
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End point timeframe |
24 hours
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| No statistical analyses for this end point | ||||||||||
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End point title |
Days on mechanical ventilation, median | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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| No statistical analyses for this end point | |||||||||||||
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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 |
30 days
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| No statistical analyses for this end point | |||||||||||||
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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 |
30 days
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| No statistical analyses for this end point | ||||||||||
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End point title |
Glasgow Outcome Scale Score | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Values of 1-8 can be obtained
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Intensive Care Unit admission | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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| No statistical analyses for this end point | ||||||||||
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End point title |
ICU length of stay | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Hospital length of stay | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
In-hospital
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Adverse event reporting additional description |
As this group of patients is expected to have a lot of complications, we will report ONLY serious adverse events (SAE) and adverse events related to study outcome: pulmonary complications, sepsis and surgical site infecton.
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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 |
As this group of patients is expected to have a lot of complications, we will report ONLY serious adverse events (SAE). Investigator will report them to the sponsor within 24 hours. SAEs consist of events that result in death, are life threatening, involve hospitalization, are permanently debilitating or involve a congenital anomaly. Furthermore, we will report adverse events related to our study outcomes: - All pulmonary complications (Pneumonia, ALI, ARDS, atelectasis) - Sepsis - SSI …before the time of discharge. | |||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liberal oxygen treatment
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Reporting group description |
As this group of patients is expected to have a lot of complications, we will report ONLY serious adverse events (SAE). Investigator will report them to the sponsor within 24 hours. SAEs consist of events that result in death, are life threatening, involve hospitalization, are permanently debilitating or involve a congenital anomaly. Furthermore, we will report adverse events related to our study outcomes: - All pulmonary complications (Pneumonia, ALI, ARDS, atelectasis) - Sepsis - SSI …before the time of discharge. | |||||||||||||||||||||||||||||||||||||||
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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 reported | |||
