INACHOS: Intermediate Normal Versus High Normal Oxygen Levels in the Emergency Department for Severe Traumatic Brain Injury

Sponsor

Evangelismos Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05464277

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury Acute Respiratory Failure Acute Respiratory Distress Syndrome Acute Brain Injury	Other: Oxygen	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

To avoid selection bias, the allocation sequence will be blinded from researchers involved in patient enrolment. Although study subjects will be unaware of the assigned group, blinding of treating clinicians is not considered feasible.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intermediate normal oxygen For the "intermediate normal oxygen" group, an oxygen saturation by pulse oximetry (SpO2) of 95-97% will be recommended in the light of the Improving Oxygen Therapy in Acute-illness (IOTA) meta-analysis. The acceptable lower limit of PaO2 will be set to 80 mmHg according to a recent consensus of experts endorsed by the European Society of Intensive Care Medicine. The lower-limit and higher-limit monitor alarm for SpO2 will be set at 94% and 98%, respectively. In case that the emergency department of a study site uses ventilators, which allow for only two options of FiO2 titration (namely, "air mix" and "FiO2 of 1.0"), then the "intermediate normal oxygen" group should receive "air mix".	Other: Oxygen Oxygen to achieve assigned SpO2 (or FiO2) targets will be administered to study subjects. The treating clinician can alter oxygenation targets at any time if deemed necessary. The oxygenation goal will be based on SpO2 rather than arterial oxygen saturation (SaO2) or arterial pressure oxygen (PaO2) from arterial blood gases. However, PaO2 can be used instead in situations where the treating clinician considers that peripheral perfusion is poor or SpO2 readings are unreliable. Assigned SpO2 targets will apply to the study subjects for a total duration of 6 hours from intubation or until death or until transfer to the operating theater (whatever comes first).
Active Comparator: High normal oxygen For the "high normal oxygen" group, an oxygen saturation by pulse oximetry (SpO2) of 99-100% will be recommended. The lower-limit monitor alarm for SpO2 will be set at 98%. No upper alarm limit for SpO2 will be set. In case that the emergency department of a study site uses ventilators, which allow for only two options of FiO2 titration (namely, "air mix" and "FiO2 of 1.0"), then the "high normal oxygen" group should receive "FiO2 of 1.0".	Other: Oxygen Oxygen to achieve assigned SpO2 (or FiO2) targets will be administered to study subjects. The treating clinician can alter oxygenation targets at any time if deemed necessary. The oxygenation goal will be based on SpO2 rather than arterial oxygen saturation (SaO2) or arterial pressure oxygen (PaO2) from arterial blood gases. However, PaO2 can be used instead in situations where the treating clinician considers that peripheral perfusion is poor or SpO2 readings are unreliable. Assigned SpO2 targets will apply to the study subjects for a total duration of 6 hours from intubation or until death or until transfer to the operating theater (whatever comes first).

Arm

Intervention/Treatment

Active Comparator: Intermediate normal oxygen

For the "intermediate normal oxygen" group, an oxygen saturation by pulse oximetry (SpO2) of 95-97% will be recommended in the light of the Improving Oxygen Therapy in Acute-illness (IOTA) meta-analysis. The acceptable lower limit of PaO2 will be set to 80 mmHg according to a recent consensus of experts endorsed by the European Society of Intensive Care Medicine. The lower-limit and higher-limit monitor alarm for SpO2 will be set at 94% and 98%, respectively. In case that the emergency department of a study site uses ventilators, which allow for only two options of FiO2 titration (namely, "air mix" and "FiO2 of 1.0"), then the "intermediate normal oxygen" group should receive "air mix".

Other: Oxygen

Oxygen to achieve assigned SpO2 (or FiO2) targets will be administered to study subjects. The treating clinician can alter oxygenation targets at any time if deemed necessary. The oxygenation goal will be based on SpO2 rather than arterial oxygen saturation (SaO2) or arterial pressure oxygen (PaO2) from arterial blood gases. However, PaO2 can be used instead in situations where the treating clinician considers that peripheral perfusion is poor or SpO2 readings are unreliable. Assigned SpO2 targets will apply to the study subjects for a total duration of 6 hours from intubation or until death or until transfer to the operating theater (whatever comes first).

Active Comparator: High normal oxygen

For the "high normal oxygen" group, an oxygen saturation by pulse oximetry (SpO2) of 99-100% will be recommended. The lower-limit monitor alarm for SpO2 will be set at 98%. No upper alarm limit for SpO2 will be set. In case that the emergency department of a study site uses ventilators, which allow for only two options of FiO2 titration (namely, "air mix" and "FiO2 of 1.0"), then the "high normal oxygen" group should receive "FiO2 of 1.0".

Other: Oxygen

Outcome Measures

Primary Outcome Measures

Mean area-under-curve (AUC) for SpO2 [Measurements will be obtained each hour for a total duration of 6 hours from intubation.]
SpO2 will be recorded each hour for a total duration of 6 hours from intubation. Subsequently, mean area-under-curve (AUC) will be calculated for each group. This will demonstrate the feasibility of the study.
Mean area-under-curve (AUC) for FiO2 [Measurements will be obtained each hour for a total duration of 6 hours from intubation.]
FiO2 will be recorded each hour for a total duration of 6 hours from intubation. Subsequently, mean area-under-curve (AUC) will be calculated for each group. This will demonstrate the feasibility of the study.
PaO2 [Measurements will be obtained at least once during 6 hours from intubation.]
PaO2 will be recorded at least once during 6 hours from intubation. Subsequently, PaO2 values (mmHg) will be calculated for each group. This will demonstrate the feasibility of the study.

Secondary Outcome Measures

Nosocomial pneumonia [Within 7 days of subject enrollment]
Incidence of nosocomial pneumonia will be recorded for each arm
Acute Respiratory Distress Syndrome (ARDS) [Within 7 days of subject enrollment]
Incidence of ARDS will be recorded for each arm
All-cause mortality [Within 28 days of subject enrollment]
All-cause mortality will be recorded during ICU stay
Extended Glasgow Outcome Score (GOS-E) [At 6 months following subject enrollment]
A combined outcome of disability and mortality at 6 months using the Extended Glasgow Outcome Score will be assessed