Clinical trial NCT02407028: Hyperbaric Oxygen Brain Injury Treatment Trial
Official title: Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Traumatic Brain Injury
Lead sponsor: Hennepin Healthcare Research Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Strategies to Innovate EmeRgENcy Care Clinical Trials Network
First posted: 2015-04-02
Enrollment: 200
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Glasgow Outcome Scale Extended (GOS-E)
timeFrame: Assessment at 6 months
Secondary outcomes:
measure: Duration of ICP elevation
timeFrame: First 5 days
measure: Therapeutic intensity level scores for controlling intracranial pressure (ICP)
timeFrame: First 5 days
measure: Brain tissue partial pressure of oxygen
timeFrame: First 5 days
measure: Serious adverse events
timeFrame: 180 days
measure: Peak brain tissue oxygen (P02) during HBO treatments
timeFrame: First 5 days
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Medical Center - Hillcrest Hospital
state: California
city: West Palm Beach
country: United States
facility: St. Mary's Medical Center
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Hospital
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Hospital
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Hamilton
country: Canada
facility: Hamilton Heath Services
state: Ontario
Study officials:
affiliation: Hennepin County Medical Center, Minneapolis
name: Gaylan L Rockswold, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: William Barsan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kansas Medical Center
name: Byron Gajewski, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Frederick K Korley, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.