NCT02407028

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for phase_2

Timeline
38mo left

Started Jun 2018

Longer than P75 for phase_2

Geographic Reach
2 countries

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress72%
Jun 2018Jun 2029

First Submitted

Initial submission to the registry

March 18, 2015

Completed
15 days until next milestone

First Posted

Study publicly available on registry

April 2, 2015

Completed
3.2 years until next milestone

Study Start

First participant enrolled

June 25, 2018

Completed
10.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 26, 2028

Expected
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2029

Last Updated

October 3, 2025

Status Verified

August 1, 2025

Enrollment Period

10.3 years

First QC Date

March 18, 2015

Last Update Submit

September 30, 2025

Conditions

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

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)

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)

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)

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)

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)

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)

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)

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

Also known as: Standard of Care
Usual care

Eligibility Criteria

Age16 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

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

RECRUITING

Duke University Hospital

Durham, North Carolina, 27710, United States

RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

ACTIVE NOT RECRUITING

Hamilton Heath Services

Hamilton, Ontario, L8L 2X2, Canada

ACTIVE NOT RECRUITING

Related Publications (4)

  • 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: 31070807BACKGROUND
  • 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: 27306921BACKGROUND
  • 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: 19852540BACKGROUND
  • 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: 23510092BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Brain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

Quality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth 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

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

October 3, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will not share

Locations