Hyperbaric Oxygen Brain Injury Treatment Trial (HOBIT)

Gaylan Rockswold

Status and phase: Enrolling; Phase 2

Conditions: Traumatic Brain Injury

Treatments: Drug: Hyperbaric oxygen (2.5 ATA + NBH); Drug: Hyperbaric oxygen (2.0 ATA + NBH); Other: Usual Care; Drug: Hyperbaric oxygen (1.5 ATA + NBH); Drug: Hyperbaric oxygen (2.5 ATA, no NBH); Drug: Hyperbaric oxygen (2.0 ATA, no NBH); Drug: Normobaric Hyperoxia (NBH); Drug: Hyperbaric oxygen (1.5 ATA, no NBH)

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT02407028

GLR-NIH-2015

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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200 participants in 8 patient groups

Hyperbaric oxygen (1.5 ATA, no NBH)

Experimental group

Description:

Hyperbaric oxygen at 1.5 ATA for 1 hour without NBH. This treatment is administered twice a day for 5 days.

Treatment:

Drug: Hyperbaric oxygen (1.5 ATA, no NBH)

Hyperbaric oxygen (2.0 ATA, no NBH)

Experimental group

Description:

Hyperbaric oxygen at 2.0 ATA for 1 hour without NBH. This treatment is administered twice a day for 5 days.

Treatment:

Drug: Hyperbaric oxygen (2.0 ATA, no NBH)

Hyperbaric oxygen (2.5 ATA, no NBH)

Experimental group

Description:

Hyperbaric oxygen at 2.5 ATA for 1 hour, without NBH. This treatment is administered twice a day for 5 days.

Treatment:

Drug: Hyperbaric oxygen (2.5 ATA, no NBH)

Hyperbaric oxygen (1.5 ATA + NBH)

Experimental group

Description:

Hyperbaric oxygen at 1.5 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days.

Treatment:

Drug: Hyperbaric oxygen (1.5 ATA + NBH)

Hyperbaric oxygen (2.0 ATA + NBH)

Experimental group

Description:

Hyperbaric oxygen at 2.0 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days.

Treatment:

Drug: Hyperbaric oxygen (2.0 ATA + NBH)

Hyperbaric oxygen (2.5 ATA + NBH)

Experimental group

Description:

Hyperbaric oxygen at 2.5 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days.

Treatment:

Drug: Hyperbaric oxygen (2.5 ATA + NBH)

Normobaric Hyperoxia (NBH)

Experimental group

Description:

Normobaric Hyperoxia (NBH meaning 100% O2 at 1.0 ATA) for 4.5 hours twice a day for 5 days.

Treatment:

Drug: Normobaric Hyperoxia (NBH)

Usual care

Active Comparator group

Description:

Usual care for severe TBI

Treatment:

Other: Usual Care