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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
| Strategies to Innovate EmeRgENcy Care Clinical Trials Network | NETWORK |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Glasgow Outcome Scale Extended (GOS-E) | Assessment at 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of ICP elevation | The duration of ICP elevation will be measured using the area under the curve methodology | First 5 days |
| Therapeutic intensity level scores for controlling intracranial pressure (ICP) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gaylan L. Rockswold, M.D., Ph.D. | Contact | 612-873-2810 | gaylan.rockswold@hcmed.org |
| Name | Affiliation | Role |
|---|---|---|
| Gaylan L Rockswold, M.D., Ph.D. | Hennepin County Medical Center, Minneapolis | Principal Investigator |
| William Barsan, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSD Medical Center - Hillcrest Hospital | Recruiting | San Diego | California | 92103 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19852540 | Background | 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. | |
| 23510092 |
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| 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. |
|
| Normobaric Hyperoxia (NBH) | Experimental | Normobaric Hyperoxia (NBH meaning 100% O2 at 1.0 ATA) for 4.5 hours twice a day for 5 days. |
|
| Usual care | Active Comparator | Usual care for severe TBI |
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| 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 |
|
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| 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 |
|
|
| 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 |
|
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| 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 |
|
|
| 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 |
|
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| 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 |
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| Usual Care | Other | Will be treated with usual and customary care for severe traumatic brain injury |
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This tracks the level of therapies used to control ICP during the first 5 days
| First 5 days |
| Brain tissue partial pressure of oxygen | This outcome will be measured only in patients with LICOX monitoring | First 5 days |
| 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 |
| 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 |
| Byron Gajewski, Ph.D. |
| University of Kansas Medical Center |
| Principal Investigator |
| Frederick K Korley, M.D., Ph.D. | University of Michigan | Principal Investigator |
| St. Mary's Medical Center | Recruiting | West Palm Beach | Florida | 33407 | United States |
|
| University of Iowa Hospitals and Clinics | Recruiting | Iowa City | Iowa | 52242 | United States |
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| University of Kentucky Hospital | Recruiting | Lexington | Kentucky | 40536 | United States |
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| University of Maryland | Recruiting | Baltimore | Maryland | 21201 | United States |
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| Detroit Receiving Hospital | Recruiting | Detroit | Michigan | 48201 | United States |
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| Hennepin County Hospital | Recruiting | Minneapolis | Minnesota | 55415 | United States |
|
| University of Nebraska Medical Center | Completed | Omaha | Nebraska | 68198 | United States |
| Duke University Hospital | Recruiting | Durham | North Carolina | 27710 | United States |
|
| The Ohio State University Wexner Medical Center | Completed | Columbus | Ohio | 43210 | United States |
| Hamilton Heath Services | Completed | Hamilton | Ontario | L8L 2X2 | Canada |
| 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. |
| 41446562 | Result | 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. |
| 37009524 | 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. |
| 37599009 | 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. |
| 41214784 | 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. |
| 38885949 | 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. |
| 32664792 | 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. |
| 31070807 | 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. |
| 27306921 | 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. |
| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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