Clinical trial NCT05464277: Intermediate Normal Versus High Normal Oxygen Levels in the Emergency Department for Severe Traumatic Brain Injury
Official title: Impact of Intermediate Normal Compared to High Normal Oxygen Levels on Outcomes of Patients Presenting in the Emergency Department With Severe Traumatic Brain Injury (INACHOS): a Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Traumatic Brain Injury
Acute Respiratory Failure
Acute Respiratory Distress Syndrome
Acute Brain Injury
Keywords: emergency care
acute respiratory failure
trauma
oxygen
disability
acute care
critical care
mortality
brain injury
mechanical ventilation
Lead sponsor: Evangelismos Hospital
Sponsor class: OTHER
First posted: 2022-07-19
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Enrolled patients will be randomly allocated using opaque sealed envelopes to either "intermediate normal oxygen" or "high normal oxygen" group. The asymptomatic maximal procedure, with an allocation ratio of 1:1 and a maximum tolerated imbalance of 2 will be used to randomize subjects.
Primary purpose: TREATMENT

Brief summary: Despite almost universal usage of supplemental oxygen therapy in patients presenting in the emergency department with traumatic brain injury (TBI), optimal oxygen levels are unclear.

The investigators propose a pilot multi-center randomized controlled trial to test the hypothesis that maintaining intermediate normal as opposed to high normal oxygen levels in patients presenting in the emergency department with TBI is feasible, and to obtain preliminary data on the efficacy of the two approaches to oxygen therapy. The aim is that the investigators produce pilot data, which could inform the design of potential subsequent larger clinical trials.

Detailed description: Despite the worldwide burden of traumatic brain injury (TBI), medical research on the field as opposed to other health problems is underrepresented. Consequently, there are few data to support commonly used interventions for the management of TBI, especially in the setting of the emergency department. For example, despite almost universal usage of supplemental oxygen therapy, the effects of different oxygenation levels under normobaric conditions on outcomes of patients presenting in the emergency department with TBI are unknown.

On the one hand, liberal oxygenation may provide a margin of safety against hypoxemia and may be needed to meet the high oxygen demands of an acutely altered brain physiology. On the other hand, there are increasing concerns that excessive oxygen supplementation may have harmful effects, such as central nervous system toxicity, cerebral vasoconstriction, impaired immunity leading to predisposition to infections (including pneumonia) and acute lung injury/acute respiratory distress syndrome. Such effects could be avoided by intermediate normal oxygen levels.

Taken together, the relative merits and risks of the abovementioned two approaches to oxygen therapy (namely, intermediate normal versus high normal oxygen levels) of patients with TBI in terms of important clinical outcomes (namely, development of nosocomial pneumonia, acute respiratory distress syndrome, disability and mortality) remain undefined. This suggests the need for randomized controlled trials. However, randomized controlled trials focusing on patient-centered outcomes should be preceded by pilot randomized controlled trials, which demonstrate a separation in treatment and protocol compliance (feasibility) associated with the studied interventions.

Therefore, the investigators propose a pilot multi-center randomized controlled trial to test the hypothesis that maintaining intermediate normal as opposed to high normal oxygen levels in patients presenting in the emergency department with TBI is feasible, and to obtain preliminary data on the efficacy of the two approaches to oxygen therapy.

Eligibility criteria: Inclusion Criteria:

* Adult patient ≥18 years
* Glasgow Coma Scale ≤ 8
* Non-penetrating traumatic brain injury
* Intubated patient

Exclusion Criteria:

* Age \<18 years
* Lack of intention to admit to the intensive care unit
* Moribund patient expected to die within 24 hours
* Expected need for mechanical ventilation \< 24 hours
* Time interval from intubation to group allocation more than 60 minutes
* Penetrating traumatic brain injury
* Pregnancy
* Lack of equipoise of the treating clinician
* Lack of informed consent

Primary outcomes:
measure: Mean area-under-curve (AUC) for SpO2
timeFrame: Measurements will be obtained each hour for a total duration of 6 hours from intubation.
measure: Mean area-under-curve (AUC) for FiO2
timeFrame: Measurements will be obtained each hour for a total duration of 6 hours from intubation.
measure: PaO2
timeFrame: Measurements will be obtained at least once during 6 hours from intubation.
Secondary outcomes:
measure: Nosocomial pneumonia
timeFrame: Within 7 days of subject enrollment
measure: Acute Respiratory Distress Syndrome (ARDS)
timeFrame: Within 7 days of subject enrollment
measure: All-cause mortality
timeFrame: Within 28 days of subject enrollment
measure: Extended Glasgow Outcome Score (GOS-E)
timeFrame: At 6 months following subject enrollment
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Evangelismos Hospital
city: Athens
country: Greece
facility: KAT General Hospital
Study officials:
affiliation: Evangelismos Hospital, Athens, Greece
name: Ilias I Siempos, MD, DSc
role: PRINCIPAL_INVESTIGATOR
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