HOBIT: Hyperbaric Oxygen Brain Injury Treatment Trial
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
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
Other Names:
|
| Experimental: 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. |
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
Other Names:
|
| Experimental: 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. |
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
Other Names:
|
| Experimental: 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. |
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
Other Names:
|
| Experimental: 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. |
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
Other Names:
|
| Experimental: 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. |
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
Other Names:
|
| Experimental: Normobaric Hyperoxia (NBH) Normobaric Hyperoxia (NBH meaning 100% O2 at 1.0 ATA) for 4.5 hours twice a day for 5 days. |
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
Other Names:
|
| Active Comparator: Usual care Usual care for severe TBI |
Other: Usual Care
Will be treated with usual and customary care for severe traumatic brain injury
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Glasgow Outcome Scale Extended (GOS-E) [Assessment at 6 months]
Secondary Outcome Measures
- Duration of ICP elevation [First 5 days]
The duration of ICP elevation will be measured using the area under the curve methodology
- Therapeutic intensity level scores for controlling intracranial pressure (ICP) [First 5 days]
This tracks the level of therapies used to control ICP during the first 5 days
- Brain tissue partial pressure of oxygen [First 5 days]
This outcome will be measured only in patients with LICOX monitoring
- Serious adverse events [180 days]
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
- Peak brain tissue oxygen (P02) during HBO treatments [First 5 days]
To examine the association between peak brain tissue PO2 during hyperbaric treatment and favorable outcome at 6-months (measured by the GOS-E).
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCSD Medical Center - Hillcrest Hospital | San Diego | California | United States | 92103 |
| 2 | St. Mary's Medical Center | West Palm Beach | Florida | United States | 33407 |
| 3 | University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
| 4 | University of Kentucky Hospital | Lexington | Kentucky | United States | 40536 |
| 5 | University of Maryland | Baltimore | Maryland | United States | 21201 |
| 6 | Detroit Receiving Hospital | Detroit | Michigan | United States | 48201 |
| 7 | Hennepin County Hospital | Minneapolis | Minnesota | United States | 55415 |
| 8 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 9 | Duke University Hospital | Durham | North Carolina | United States | 27710 |
| 10 | The Ohio State University Wexner Medical Center | Columbus | Ohio | United States | 43210 |
| 11 | Hamilton Heath Services | Hamilton | Ontario | Canada | L8L 2X2 |
Sponsors and Collaborators
- Hennepin Healthcare Research Institute
- National Institute of Neurological Disorders and Stroke (NINDS)
- Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network
Investigators
- Principal Investigator: 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
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- GLR-NIH-2015