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Purpose

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

Eligibility

Eligible Ages
Between 16 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Factorial Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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:
    • 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 names:
    • 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 names:
    • 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 names:
    • 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 names:
    • 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 names:
    • 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 names:
    • 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 names:
    • Standard of Care

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky Hospital
Lexington, Kentucky 40536
Contact:
Joann Short
joann.short@uky.edu

More Details

NCT ID
NCT02407028
Status
Recruiting
Sponsor
Hennepin Healthcare Research Institute

Study Contact

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

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.