Hyperbaric Oxygen Brain Injury Treatment Trial

Study Overview
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Brief Summary
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The purpose of this innovative adaptive phase II trial design is to determine the optimal combination of hyperbaric oxygen treatment parameters that is most likely to demonstrate improvement in the outcome of severe TBI patients in a subsequent phase III trial.

Detailed Description
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Preclinical and clinical investigations strongly indicate that hyperbaric oxygen (HBO2) is physiologically active in improving the destructive processes in severe Traumatic Brain Injury (TBI). However, prior to a definitive efficacy study, important information is required regarding optimizing the HBO2 treatment paradigm instituted in terms of pressure and whether NBH enhances the clinical effectiveness of the HBO2 treatment. Preclinical investigators working with TBI models have used pressures varying from 1.5 to 3.0 atmospheres absolute (ATA). Clinical investigators have used pressure varying from 1.5 to 2.5 ATA. However, the lungs in severe TBI patients have frequently been compromised by direct lung injury and/or acquired ventilator pneumonia and are susceptible to oxygen (O2) toxicity. Working within these constraints, it is essential to determine the most effective HBO2 treatment parameters without producing O2 toxicity and clinical complications. This proposed clinical trial is designed to answer these questions and to provide important data to plan a definitive efficacy trial.

Official Title
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Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Drug: Hyperbaric oxygen (1.5 ATA, no NBH)
* Drug: Hyperbaric oxygen (2.0 ATA, no NBH)
* Drug: Hyperbaric oxygen (2.5 ATA, no NBH)
* Drug: Hyperbaric oxygen (1.5 ATA + NBH)
* Drug: Hyperbaric oxygen (2.0 ATA + NBH)
* Drug: Hyperbaric oxygen (2.5 ATA + NBH)
* Drug: Normobaric Hyperoxia (NBH)
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16 years or older and 65 years or younger Present with severe TBI, defined as Glasgow Coma Scale (GCS) of 3 to 8. Marshall computerized tomography (CT) score >1 in patients with a GCS of 7 or 8 or patients with an alcohol level >200 mg/dl Ability to initiate the first hyperbaric oxygen treatment within 8 hours of admission in patients not requiring a craniotomy/craniectomy or any other major surgical procedure OR Ability to initiate the first hyperbaric oxygen treatment within 14 hours of admission in patients requiring a craniotomy/craniectomy or major surgical procedure Exclusion Criteria: First hyperbaric oxygen treatment cannot be initiated within 24 hours of injury GCS of 3 with mid-position and non-reactive pupils bilaterally (4mm) Penetrating head injury Pregnant Pre-existing neurologic disease (e.g. TBI or stroke or neurodegenerative disorder) with confounding residual neurologic deficits Unstable acute spinal cord injury Fixed coagulopathy Severe hypoxia Cardiopulmonary resuscitation performed Coma suspected to de due to primarily non-TBI causes Any contraindications to the study intervention

Ages Eligible for Study
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Minimum Age: 16 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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric oxygen (1.5 ATA, no NBH)<br>Hyperbaric oxygen at 1.5 ATA for 1 hour without NBH. This treatment is administered twice a day for 5 days. | Drug: Hyperbaric oxygen (1.5 ATA, no NBH)<br>* HBO at 1.5 ATA for 60 minutes without NBH. Treatment will be twice a day for five days or until patient is following commands or brain dead<br>* Other names: HBO;|
| Experimental: Hyperbaric oxygen (2.0 ATA, no NBH)<br>Hyperbaric oxygen at 2.0 ATA for 1 hour without NBH. This treatment is administered twice a day for 5 days. | Drug: Hyperbaric oxygen (2.0 ATA, no NBH)<br>* HBO at 2.0 ATA for 60 minutes without NBH. Treatment will be twice a day for five days or until patient is following commands or brain dead<br>* Other names: HBO;|
| Experimental: Hyperbaric oxygen (2.5 ATA, no NBH)<br>Hyperbaric oxygen at 2.5 ATA for 1 hour, without NBH. This treatment is administered twice a day for 5 days. | Drug: Hyperbaric oxygen (2.5 ATA, no NBH)<br>* HBO at 2.5 ATA for 60 minutes without NBH. Treatment will be twice a day for five days or until patient is following commands or brain dead<br>* Other names: HBO;|
| Experimental: Hyperbaric oxygen (1.5 ATA + NBH)<br>Hyperbaric oxygen at 1.5 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days. | Drug: Hyperbaric oxygen (1.5 ATA + NBH)<br>* HBO at 1.5 ATA for 60 minutes followed by NBH for 3 hours. Treatment will be twice a day for five days or until patient is following commands or brain dead<br>* Other names: HBO;|
| Experimental: Hyperbaric oxygen (2.0 ATA + NBH)<br>Hyperbaric oxygen at 2.0 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days. | Drug: Hyperbaric oxygen (2.0 ATA + NBH)<br>* HBO at 2.0 ATA for 60 minutes followed by NBH for 3 hours. Treatment will be twice a day for five days or until patient is following commands or brain dead<br>* Other names: HBO;|
| Experimental: Hyperbaric oxygen (2.5 ATA + NBH)<br>Hyperbaric oxygen at 2.5 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days. | Drug: Hyperbaric oxygen (2.5 ATA + NBH)<br>* HBO at 2.5 ATA for 60 minutes followed by NBH for 3 hours. Treatment will be twice a day for five days or until patient is following commands or brain dead<br>* Other names: HBO;|
| Experimental: Normobaric Hyperoxia (NBH)<br>Normobaric Hyperoxia (NBH meaning 100% O2 at 1.0 ATA) for 4.5 hours twice a day for 5 days. | Drug: Normobaric Hyperoxia (NBH)<br>* 100% fraction of inspired oxygen (FiO2) for 4.5 hours twice a day for five days or until patient following commands or brain dead<br>* Other names: NBH;|
| Active Comparator: Usual care<br>Usual care for severe TBI | Other: Usual Care<br>* Will be treated with usual and customary care for severe traumatic brain injury<br>* Other names: Standard of Care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glasgow Outcome Scale Extended (GOS-E) |  | Assessment at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of ICP elevation | The duration of ICP elevation will be measured using the area under the curve methodology | First 5 days | 
| Therapeutic intensity level scores for controlling intracranial pressure (ICP) | This tracks the level of therapies used to control ICP during the first 5 days | First 5 days | 
| Brain tissue partial pressure of oxygen | This outcome will be measured only in patients with LICOX monitoring | First 5 days | 
| Serious adverse events | Events resulting in death, a life-threatening adverse event, or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions | 180 days | 
| Peak brain tissue oxygen (P02) during HBO treatments | To examine the association between peak brain tissue PO2 during hyperbaric treatment and favorable outcome at 6-months (measured by the GOS-E). | First 5 days |