Hyperbaric Oxygen Brain Injury Treatment Trial

NCT ID: NCT02407028

Last Updated: 2025-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-25

Study Completion Date

2029-06-30

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.

Conditions

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Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Hyperbaric oxygen (1.5 ATA, no NBH)

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

Group Type EXPERIMENTAL

Hyperbaric oxygen (1.5 ATA, no NBH)

Intervention Type DRUG

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

Hyperbaric oxygen (2.0 ATA, no NBH)

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

Group Type EXPERIMENTAL

Hyperbaric oxygen (2.0 ATA, no NBH)

Intervention Type DRUG

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

Hyperbaric oxygen (2.5 ATA, no NBH)

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

Group Type EXPERIMENTAL

Hyperbaric oxygen (2.5 ATA, no NBH)

Intervention Type DRUG

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

Hyperbaric oxygen (1.5 ATA + NBH)

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

Group Type EXPERIMENTAL

Hyperbaric oxygen (1.5 ATA + NBH)

Intervention Type DRUG

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

Hyperbaric oxygen (2.0 ATA + NBH)

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

Group Type EXPERIMENTAL

Hyperbaric oxygen (2.0 ATA + NBH)

Intervention Type DRUG

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

Hyperbaric oxygen (2.5 ATA + NBH)

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

Group Type EXPERIMENTAL

Hyperbaric oxygen (2.5 ATA + NBH)

Intervention Type DRUG

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

Normobaric Hyperoxia (NBH)

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

Group Type EXPERIMENTAL

Normobaric Hyperoxia (NBH)

Intervention Type DRUG

100% fraction of inspired oxygen (FiO2) for 4.5 hours twice a day for five days or until patient following commands or brain dead

Usual care

Usual care for severe TBI

Group Type ACTIVE_COMPARATOR

Usual Care

Intervention Type OTHER

Will be treated with usual and customary care for severe traumatic brain injury

Interventions

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Hyperbaric oxygen (1.5 ATA, no NBH)

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

Intervention Type DRUG

Hyperbaric oxygen (2.0 ATA, no NBH)

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

Intervention Type DRUG

Hyperbaric oxygen (2.5 ATA, no NBH)

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

Intervention Type DRUG

Hyperbaric oxygen (1.5 ATA + NBH)

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

Intervention Type DRUG

Hyperbaric oxygen (2.0 ATA + NBH)

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

Intervention Type DRUG

Hyperbaric oxygen (2.5 ATA + NBH)

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

Intervention Type DRUG

Normobaric Hyperoxia (NBH)

100% fraction of inspired oxygen (FiO2) for 4.5 hours twice a day for five days or until patient following commands or brain dead

Intervention Type DRUG

Usual Care

Will be treated with usual and customary care for severe traumatic brain injury

Intervention Type OTHER

Other Intervention Names

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HBO HBO HBO HBO HBO HBO NBH Standard of Care

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
Minimum Eligible Age

16 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Strategies to Innovate EmeRgENcy Care Clinical Trials Network

NETWORK

Sponsor Role collaborator

Gaylan Rockswold

OTHER

Sponsor Role lead

Responsible Party

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Gaylan Rockswold

M.D., Neurosurgery

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Gaylan L Rockswold, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hennepin County Medical Center, Minneapolis

William Barsan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Byron Gajewski, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Frederick K Korley, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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UCSD Medical Center - Hillcrest Hospital

San Diego, California, United States

Site Status RECRUITING

St. Mary's Medical Center

West Palm Beach, Florida, United States

Site Status RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

University of Kentucky Hospital

Lexington, Kentucky, United States

Site Status RECRUITING

University of Maryland

Baltimore, Maryland, United States

Site Status RECRUITING

Detroit Receiving Hospital

Detroit, Michigan, United States

Site Status RECRUITING

Hennepin County Hospital

Minneapolis, Minnesota, United States

Site Status RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status RECRUITING

Duke University Hospital

Durham, North Carolina, United States

Site Status RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Hamilton Heath Services

Hamilton, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Canada

Central Contacts

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Gaylan L. Rockswold, M.D., Ph.D.

Role: CONTACT

612-873-2810

Facility Contacts

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Lilian Von Husen

Role: primary

Tracy RODRIGUEZ

Role: primary

Catherine Fairfield

Role: primary

Ronda A Ronda PETREY

Role: primary

Leslie Sult

Role: primary

Nick Wesner

Role: primary

Jessica Gieseke

Role: primary

Brooklin K Zimmerman

Role: primary

Tammy Hawley

Role: primary

References

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Gajewski BJ, Meinzer C, Berry SM, Rockswold GL, Barsan WG, Korley FK, Martin RH. Bayesian hierarchical EMAX model for dose-response in early phase efficacy clinical trials. Stat Med. 2019 Jul 30;38(17):3123-3138. doi: 10.1002/sim.8167. Epub 2019 May 9.

Reference Type BACKGROUND
PMID: 31070807 (View on PubMed)

Gajewski BJ, Berry SM, Barsan WG, Silbergleit R, Meurer WJ, Martin R, Rockswold GL. Hyperbaric oxygen brain injury treatment (HOBIT) trial: a multifactor design with response adaptive randomization and longitudinal modeling. Pharm Stat. 2016 Sep;15(5):396-404. doi: 10.1002/pst.1755. Epub 2016 Jun 15.

Reference Type BACKGROUND
PMID: 27306921 (View on PubMed)

Rockswold SB, Rockswold GL, Zaun DA, Zhang X, Cerra CE, Bergman TA, Liu J. A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury. J Neurosurg. 2010 May;112(5):1080-94. doi: 10.3171/2009.7.JNS09363.

Reference Type BACKGROUND
PMID: 19852540 (View on PubMed)

Rockswold SB, Rockswold GL, Zaun DA, Liu J. A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg. 2013 Jun;118(6):1317-28. doi: 10.3171/2013.2.JNS121468. Epub 2013 Mar 19.

Reference Type BACKGROUND
PMID: 23510092 (View on PubMed)

Other Identifiers

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GLR-NIH-2015

Identifier Type: -

Identifier Source: org_study_id

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