Hyperbaric Oxygen Brain Injury Treatment Trial (HOBIT)

• ClinicalTrials.gov Identifier: NCT02407028
• Recruitment Status: Recruiting
• First Posted: April 2, 2015
• Last Update Posted: December 12, 2022
• Sponsor: Hennepin Healthcare Research Institute
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network
• Information provided by (Responsible Party): Hennepin Healthcare Research Institute

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
Traumatic Brain Injury	Drug: Hyperbaric oxygen (1.5 ATA, no NBH); Drug: Hyperbaric oxygen (2.0 ATA, no NBH); Drug: Hyperbaric oxygen (2.5 ATA, no NBH); Drug: Hyperbaric oxygen (1.5 ATA + NBH); Drug: Hyperbaric oxygen (2.0 ATA + NBH); Drug: Hyperbaric oxygen (2.5 ATA + NBH); Drug: Normobaric Hyperoxia (NBH); Other: Usual Care	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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial
• Actual Study Start Date: June 25, 2018
• Estimated Primary Completion Date: October 2026
• Estimated Study Completion Date: June 2027

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 Name: HBO
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 Name: HBO
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 Name: HBO
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 Name: HBO
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 Name: HBO
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 Name: HBO
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 Name: NBH
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 Name: Standard of Care

Outcome Measures

Primary Outcome Measures :

1. Glasgow Outcome Scale Extended (GOS-E) [ Time Frame: Assessment at 6 months ]

Secondary Outcome Measures :

1. Duration of ICP elevation [ Time Frame: First 5 days ]
   The duration of ICP elevation will be measured using the area under the curve methodology
2. Therapeutic intensity level scores for controlling intracranial pressure (ICP) [ Time Frame: First 5 days ]
   This tracks the level of therapies used to control ICP during the first 5 days
3. Brain tissue partial pressure of oxygen [ Time Frame: First 5 days ]
   This outcome will be measured only in patients with LICOX monitoring
4. Serious adverse events [ Time Frame: 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
5. Peak brain tissue oxygen (P02) during HBO treatments [ Time Frame: 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

• Ages Eligible for Study: 16 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts

Contact: Gaylan L. Rockswold, M.D., Ph.D.; 612-873-2810; gaylan.rockswold@hcmed.org

Locations

United States, California

UCSD Medical Center - Hillcrest Hospital; Recruiting

San Diego, California, United States, 92103

Contact: Terry Curry tcurry@ucsd.edu

Principal Investigator: Todd Constantini, MD

United States, Florida

St. Mary's Medical Center; Recruiting

West Palm Beach, Florida, United States, 33407

Contact: Tracy RODRIGUEZ Tracy.Rodriguez@tenethealth.com

Principal Investigator: Robert Borrego, MD

United States, Iowa

University of Iowa Hospitals and Clinics; Recruiting

Iowa City, Iowa, United States, 52242

Contact: Catherine Fairfield catherine-fairfield@uiowa.edu

Principal Investigator: Nicholas Mohr, MD

United States, Kentucky

University of Kentucky Hospital; Recruiting

Lexington, Kentucky, United States, 40536

Contact: Ronda A Ronda PETREY ronda.petrey@uky.edu

Principal Investigator: Kevin Hatton, MD

United States, Maryland

University of Maryland; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Leslie Sult lsult@som.umaryland.edu

Principal Investigator: Kinjal Sethuraman, MD

United States, Michigan

Detroit Receiving Hospital; Recruiting

Detroit, Michigan, United States, 48201

Contact: Farhan Ayaz sfayaz@med.wayne.edu

Principal Investigator: Anthony Lagina, MD

United States, Minnesota

Hennepin County Hospital; Recruiting

Minneapolis, Minnesota, United States, 55415

Contact: Chloe LAWYER lawye010@umn.edu

Principal Investigator: Tom Bergman, MD, PhD

United States, Nebraska

University of Nebraska Medical Center; Recruiting

Omaha, Nebraska, United States, 68198

Contact: Brooklin K Zimmerman brooklin.zimmerman@unmc.edu

Principal Investigator: Jeffrey Cooper, MD

United States, North Carolina

Duke University Hospital; Recruiting

Durham, North Carolina, United States, 27710

Contact: Emmalee Metzler emmalee.metzler@duke.edu

Principal Investigator: Michael James, MD

United States, Ohio

The Ohio State University Wexner Medical Center; Active, not recruiting

Columbus, Ohio, United States, 43210

Canada, Ontario

Hamilton Heath Services; Active, not recruiting

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

More Information

Publications:

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.

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.

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.

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.

• Responsible Party: Hennepin Healthcare Research Institute
• ClinicalTrials.gov Identifier: NCT02407028
• Other Study ID Numbers: GLR-NIH-2015
• First Posted: April 2, 2015
• Last Update Posted: December 12, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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