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Trial record 1 of 1 for:    NCT05146700
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Restrictive vs. Liberal Oxygen in Trauma (TRAUMOX2)

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ClinicalTrials.gov Identifier: NCT05146700
Recruitment Status : Recruiting
First Posted : December 7, 2021
Last Update Posted : May 18, 2022
Sponsor:
Collaborator:
The Novo Nordic Foundation
Information provided by (Responsible Party):
Jacob Steinmetz, Rigshospitalet, Denmark

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).


Condition or disease Intervention/treatment Phase
Trauma Oxygen Toxicity Wounds and Injuries Drug: Restrictive oxygen Drug: Liberal oxygen Phase 4

Detailed Description:

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1420 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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%

Masking: Single (Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
Official Title: Comparing Restrictive vs. Liberal Oxygen Strategies for Trauma Patients: The TRAUMOX2 Trial
Actual Study Start Date : December 10, 2021
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : June 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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

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

Active Comparator: 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%

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%




Primary Outcome Measures :
  1. The incidence of 30-day mortality and/or major respiratory complications (pneumonia and acute respiratory distress syndrome) within 30 days (combined primary endpoint) [ Time Frame: Day 30 after enrollment ]
    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


Secondary Outcome Measures :
  1. 30-day mortality [ Time Frame: Day 30 after enrollment ]
    Assessed in the patient's medical record/register

  2. 12-month mortality [ Time Frame: 12 months after enrollment ]
    Assessed in the patient's medical record/register

  3. Major respiratory complications (pneumonia and acute respiratory distress syndrome) within 30 days [ Time Frame: Day 30 after enrollment ]
    Data from the combined primary endpoint assessment

  4. Hospital length of stay [ Time Frame: From date of admission to discharge from the hospital, up to 12 months after enrollment ]
    Number of days

  5. ICU length of stay [ Time Frame: From date of admission to discharge from the ICU, up to 12 months after enrollment ]
    Number of days

  6. Time on mechanical ventilation [ Time Frame: From initiation of mechanical ventilation to being ventilator-free within 30 days after enrollment ]
    Number of hours; only mechanical ventilation in the ICU should be considered

  7. Days alive outside the ICU [ Time Frame: ICU-free days within 30 days after enrollment ]
    Number of days

  8. Days alive without mechanical ventilation [ Time Frame: Ventilator-free days within 30 days after enrollment ]
    Number of days; only mechanical ventilation in the ICU should be considered

  9. Re-intubations [ Time Frame: Within 30 days after enrollment ]
    Number of re-intubations; only re-intubations in the ICU should be considered

  10. Pneumonia post-discharge [ Time Frame: From discharge to a maximum of 30 days after enrollment ]
    Number of trial participants; evaluated through medicines prescribed after hospital discharge in countries where this information is available

  11. Episode(s) of hypoxemia during intervention (saturation <90%) [ Time Frame: During the 8 hours of the oxygen intervention arms ]
    Defined as number of times the valid oxygen saturation is below 90%; if it is below 90%, above 90% and below 90% again, then it should be registered as 2 episodes

  12. Surgical site infections [ Time Frame: Within 30 days after enrollment ]
    Defined as per the Centers for Disease Control and Prevention (CDC) criteria for a surgical site infection event

  13. 5-level EQ-5D version (EQ-5D-5L) score [ Time Frame: 6 and 12 months post-trauma ]

    Conducted through a telephone interview where the patient is asked to indicate his/her health state

    The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS)

    The EQ-5D descriptive system consists of a scale (minimum score = 5 and maximum score = 25) where the lowest score (5) indicates no problems whereas the highest score (25) indicates extreme problems

    The EQ VAS (visual analogue scale) records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled "The worst health you can imagine" (minimum score = 0) and "The best health you can imagine' (maximum score = 100)


  14. The Glasgow Outcome Scale Extended (GOSE) score [ Time Frame: 6 and 12 months post-trauma ]

    Conducted through a telephone interview where the patient/patient's next-of-kin/caretaker is interviewed through a structured questionnaire to assess the functional recovery after trauma

    The GOSE consists of a scale (minimum value = 1 and maximum value = 8); each patient given a score based on the interview:

    1 = Death, 2 = Vegetative state, 3 = Lower severe disability, 4 = Upper severe disability, 5 = Lower moderate disability, 6 = Upper moderate disability, 7 = Lower good recovery, 8 = Upper good recovery




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05146700


Contacts
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Contact: Jacob Steinmetz, MD, PhD +4535458434 jacob.steinmetz@regionh.dk
Contact: Tobias Arleth, MD +4535459502 tobias.arleth@regionh.dk

Locations
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Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8200
Contact: Mikkel Andersen, MD, PhD    +4520226661    mikkel.andersen@ph.rm.dk   
Contact: Christian Fenger-Eriksen, MD, PhD    +4578466912    chfen@dadlnet.dk   
Principal Investigator: Mikkel Andersen, MD, PhD         
Sub-Investigator: Christian Fenger-Eriksen, MD, PhD         
Rigshospitalet, Copenhagen University Hospital Recruiting
Copenhagen, Denmark, 2100
Contact: Jacob Steinmetz, MD, PhD    +4535458434    jacob.steinmetz@regionh.dk   
Contact: Tobias Arleth, MD    +4535459502    tobias.arleth@regionh.dk   
Principal Investigator: Tobias Arleth, MD         
Odense University Hospital Recruiting
Odense, Denmark, 5000
Contact: Søren Mikkelsen, Professor, MD, PhD    +4530252225    soeren.mikkelsen@rsyd.dk   
Contact: Stine Thorhauge Zwisler, MD, PhD    +4565413914    stine.zwisler@rsyd.dk   
Principal Investigator: Søren Mikkelsen, Professor, MD, PhD         
Sub-Investigator: Stine Thorhauge Zwisler, MD, PhD         
Netherlands
Erasmus MC, University Medical Center Rotterdam Recruiting
Rotterdam, Netherlands, 3000
Contact: Dr. Mark G. Van Vledder, MD, PhD    BIG-nummer 79911655801    m.vanvledder@erasmusmc.nl   
Contact: Dr. Esther M.M. Van Lieshout, PhD, MSc       e.vanlieshout@erasmusmc.nl   
Principal Investigator: Dr. Mark G. Van Vledder, MD, PhD         
Sub-Investigator: Dr. Dennis Den Hartog, MD, PhD         
Sub-Investigator: Dr. Esther M.M. Van Lieshout, PhD, MSc         
Sponsors and Collaborators
Rigshospitalet, Denmark
The Novo Nordic Foundation
Investigators
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Study Director: Jacob Steinmetz, MD, PhD Consultant
Principal Investigator: Tobias Arleth, MD Research assistent
Additional Information:
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Responsible Party: Jacob Steinmetz, MD, PhD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT05146700    
Other Study ID Numbers: 6011
2021-000556-19 ( EudraCT Number )
NNF20OC0063985 ( Other Grant/Funding Number: Novo Nordisk Fonden )
First Posted: December 7, 2021    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jacob Steinmetz, Rigshospitalet, Denmark:
Trauma
Oxygen
Additional relevant MeSH terms:
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Wounds and Injuries