Hyperbaric Oxygen Brain Injury Treatment Trial

Traumatic Brain Injury Clinical Trial

— HOBIT  

Official title:

Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02407028
• Other study ID #: GLR-NIH-2015
• Status: Recruiting
• Phase: Phase 2
• Start date: June 25, 2018
• Est. completion date: June 2027

Study information

• Verified date: February 2024
• Source: Hennepin Healthcare Research Institute
• Contact: Gaylan L. Rockswold, M.D., Ph.D.
• Phone: 612-873-2810
• Email: gaylan.rockswold[@]hcmed.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Other:
• Usual Care
Will be treated with usual and customary care for severe traumatic brain injury

Locations

Country	Name	City	State
Canada	Hamilton Heath Services	Hamilton	Ontario
United States	University of Maryland	Baltimore	Maryland
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	Duke University Hospital	Durham	North Carolina
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Kentucky Hospital	Lexington	Kentucky
United States	Hennepin County Hospital	Minneapolis	Minnesota
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UCSD Medical Center - Hillcrest Hospital	San Diego	California
United States	St. Mary's Medical Center	West Palm Beach	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Hennepin Healthcare Research Institute	National Institute of Neurological Disorders and Stroke (NINDS), Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glasgow Outcome Scale Extended (GOS-E)		Assessment at 6 months
Secondary	Duration of ICP elevation	The duration of ICP elevation will be measured using the area under the curve methodology	First 5 days
Secondary	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
Secondary	Brain tissue partial pressure of oxygen	This outcome will be measured only in patients with LICOX monitoring	First 5 days
Secondary	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
Secondary	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