Impact of Inspired Oxygen Fraction on Outcome in Patients With Traumatic Brain Injury

Study Overview
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Brief Summary
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Aim of the study is to investigate the impact of two different fractions of inspired oxygen (FiO2) on outcome in patients with severe traumatic brain injury (TBI).

Detailed Description
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The high oxygen group is treated during mechanical ventilation with either a fraction of inspired oxygen of 0.7 (high oxygen group) or a fraction of inspired oxygen 0.4 (control group). The intervention continues until withdrawal of mechanical ventilation, ICU discharge or until 14 days from ICU randomisation. Primary outcome is worse than expected outcome in the corresponding treatment arms based on outcome meas-ured by the probability of bad outcome using the CRASH® risk calculator (prognostic model for predicting outcome after traumatic brain injury). Secondary outcome is occurence of lung injury during mechanical ventilation.

Official Title
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Impact of Inspired Oxygen Fraction on Outcome in Patients With Traumatic Brain Injury

Conditions
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Traumatic Brain Injury | Patient

Intervention / Treatment
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* Other: Normobaric oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with isolated non-penetrating traumatic brain injury Multiple trauma patient with brain injury and traumas outside abdomen, thorax or pelvis not affecting oxygenation Glasgow coma scale eight or less (inclusive) Expected need for intubation and for mechanical ventilation more than 24 hours. Are recruited <18 hours after admittance to ICU and Time from TBI is less than 36 hours Informed consent from patients representative Exclusion Criteria: Age <18 or >65 years, Anticipated brain death in 12 hours (donor treatment) or otherwise moribund patient expected to die in 24 hours Expected need for mechanical ventilation less than 24 hours Insufficient oxygenation assessed by a clinician or multiple trauma patients with brain injury and severe abdominal, thoracic or pelvic injury possibly affecting oxygenation. No consent Insufficient oxygenation with the treatment modality of the lower oxygenation group (Pa02 less than 13 kPa or SpO2 95% with Fi02 40%, PEEP 10 or less) or oxygenation failure probable during ICU care (severe aspiration, multiple trauma patients with brain injury and severe abdominal, thoracic or pelvic injury possibly affecting oxygenation) Penetrating TBI No consent Suspected pregnancy (perform urinary or serological pregnancy test if suspected)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fraction of inspired oxygen of 0.4<br>Fraction of inspired normobaric oxygen of 0.4 (low oxygen group) | Other: Normobaric oxygen<br>* Fraction of inspired oxygen<br>|
| Active Comparator: Fraction of inspired oxygen of 0.7<br>Fraction of inspired normobaric oxygen of 0.7 (high oxygen group) | Other: Normobaric oxygen<br>* Fraction of inspired oxygen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glasgow outcome scale(GOS) and/or Extended glasgow outcome scale (GOSE) | The study is powered to have 80% power at 5% significance level to detect a treatment effect that decreases the proportion of poor outcome from 55% to 45%. Each patient is given an individualized tailored prognosis based on patient's baseline prognosis in a large reference population. Outcome is measured by using functional outcome score, Glasgow outcome score (GOS) and/or GOS extended (GOSE). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 month outcome | Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (GOSE 2-4) or death (GOSE 1): Occurence of lung injury during mechanical ventilation: ALI-criteria or ARDS criteria used (paO2/FiO2 ratio less than 300 or 200 respectively): Mortality at 6 months: Proportion of surviving patients with unfavourable neurological outcome at 6 months (GOSE 2-4). Quality of life assessment (EQ-5D) at 6 months: Prolonged mechanical ventilation Re-intubation rates | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TBI, Normobaric hyperoxia, Outcome, GOS, GOSE