Hyperbaric Oxygen Brain Injury Treatment Trial

NCT02407028 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GLR-NIH-2015
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 11

Brief Summary

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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Glasgow Outcome Scale Extended (GOS-E)

  Assessment at 6 months

Secondary Outcomes (5)

• Duration of ICP elevation

  First 5 days

• Therapeutic intensity level scores for controlling intracranial pressure (ICP)

  First 5 days

• Brain tissue partial pressure of oxygen

  First 5 days

• Serious adverse events

  180 days

• Peak brain tissue oxygen (P02) during HBO treatments

  First 5 days

Study Arms (8)

Hyperbaric oxygen (1.5 ATA, no NBH)

EXPERIMENTAL

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)

Hyperbaric oxygen (2.0 ATA, no NBH)

EXPERIMENTAL

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)

Hyperbaric oxygen (2.5 ATA, no NBH)

EXPERIMENTAL

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)

Hyperbaric oxygen (1.5 ATA + NBH)

EXPERIMENTAL

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)

Hyperbaric oxygen (2.0 ATA + NBH)

EXPERIMENTAL

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)

Hyperbaric oxygen (2.5 ATA + NBH)

EXPERIMENTAL

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)

Normobaric Hyperoxia (NBH)

EXPERIMENTAL

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

Drug: Normobaric Hyperoxia (NBH)

Usual care

ACTIVE COMPARATOR

Usual care for severe TBI

Other: Usual Care

Interventions

Hyperbaric oxygen (1.5 ATA, no NBH) 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

Also known as: HBO

Hyperbaric oxygen (1.5 ATA, no NBH)

Normobaric Hyperoxia (NBH) 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

Also known as: NBH

Normobaric Hyperoxia (NBH)

Hyperbaric oxygen (2.0 ATA, no NBH) 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

Also known as: HBO

Hyperbaric oxygen (2.0 ATA, no NBH)

Hyperbaric oxygen (2.5 ATA, no NBH) 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

Also known as: HBO

Hyperbaric oxygen (2.5 ATA, no NBH)

Hyperbaric oxygen (1.5 ATA + NBH) 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

Also known as: HBO

Hyperbaric oxygen (1.5 ATA + NBH)

Hyperbaric oxygen (2.0 ATA + NBH) 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

Also known as: HBO

Hyperbaric oxygen (2.0 ATA + NBH)

Hyperbaric oxygen (2.5 ATA + NBH) 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

Also known as: HBO

Hyperbaric oxygen (2.5 ATA + NBH)

Usual Care OTHER

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

Also known as: Standard of Care

Usual care

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gaylan Rockswold: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Strategies to Innovate EmeRgENcy Care Clinical Trials Network: collaborator

Study Sites (11)

UCSD Medical Center - Hillcrest Hospital

San Diego, California, 92103, United States

RECRUITING

St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kentucky Hospital

Lexington, Kentucky, 40536, United States

RECRUITING

University of Maryland

Baltimore, Maryland, 21201, United States

RECRUITING

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

RECRUITING

Hennepin County Hospital

Minneapolis, Minnesota, 55415, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

COMPLETED

Duke University Hospital

Durham, North Carolina, 27710, United States

RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

COMPLETED

Hamilton Heath Services

Hamilton, Ontario, L8L 2X2, Canada

COMPLETED

Related Publications (10)

• 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.

  PMID: 19852540 BACKGROUND

• 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.

  PMID: 23510092 BACKGROUND

• Rahman MM, Saif MSI, Beall J, Martin RL, Rockswold GL, Barsan WG, Korley FK, Silbergleit R, Stevenson V, Gajewski B. A Bayesian model with seasonal effects for predicting accrual in clinical trials: Application to HOBIT and BOOST-3 trials for severe traumatic brain injury. Contemp Clin Trials Commun. 2025 Dec 5;48:101586. doi: 10.1016/j.conctc.2025.101586. eCollection 2025 Dec.

  PMID: 41446562 RESULT

• Bantis LE, Young KJ, Tsimikas JV, Mosier BR, Gajewski B, Yeatts S, Martin RL, Barsan W, Silbergleit R, Rockswold G, Korley FK. Statistical assessment of the prognostic and the predictive value of biomarkers-A biomarker assessment framework with applications to traumatic brain injury biomarker studies. Res Methods Med Health Sci. 2023 Jan;4(1):34-48. doi: 10.1177/26320843221141056. Epub 2022 Dec 13.

  PMID: 37009524 RESULT

• Wang Y, Yeatts SD, Martin RH, Silbergleit R, Rockswold GL, Barsan WG, Korley FK, Rockswold S, Gajewski BJ. Selection of a statistical analysis method for the Glasgow Outcome Scale-Extended endpoint for estimating the probability of favorable outcome in future severe TBI clinical trials. Stat Med. 2023 Nov 10;42(25):4582-4601. doi: 10.1002/sim.9877. Epub 2023 Aug 20.

  PMID: 37599009 RESULT

• Beall J, Yeatts SD, Silbergleit R, Shutter L, Korley F, Gajewski B. Bayesian enrollment modeling for several emergency medicine clinical trials. Trials. 2025 Nov 10;26(1):483. doi: 10.1186/s13063-025-08748-3.

  PMID: 41214784 RESULT

• Shi X, Wick JA, Martin RL, Beall J, Silbergleit R, Rockswold GL, Barsan WG, Korley FK, Rockswold S, Gajewski BJ. Improved mortality analysis in early-phase dose-ranging clinical trials for emergency medical diseases using Bayesian time-to-event models with active comparators. Stat Med. 2024 Aug 30;43(19):3649-3663. doi: 10.1002/sim.10141. Epub 2024 Jun 17.

  PMID: 38885949 RESULT

• Yeatts SD, Martin RH, Meurer W, Silbergleit R, Rockswold GL, Barsan WG, Korley FK, Wright DW, Gajewski BJ. Sliding Scoring of the Glasgow Outcome Scale-Extended as Primary Outcome in Traumatic Brain Injury Trials. J Neurotrauma. 2020 Dec 15;37(24):2674-2679. doi: 10.1089/neu.2019.6969. Epub 2020 Aug 26.

  PMID: 32664792 RESULT

• 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.

  PMID: 31070807 RESULT

• 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.

  PMID: 27306921 RESULT

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Gaylan L Rockswold, M.D., Ph.D.

  Hennepin County Medical Center, Minneapolis

  PRINCIPAL INVESTIGATOR

• William Barsan, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Byron Gajewski, Ph.D.

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

• Frederick K Korley, M.D., Ph.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

612-873-2810; gaylan.rockswold@hcmed.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., Neurosurgery

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: April 2, 2015
• Study Start: June 25, 2018
• Primary Completion (Estimated): October 26, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: June 2, 2026

Record last verified: 2025-08

Locations

US (10); CA (1)