Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (TBI)
Condition: Severe Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Intervention: Management protocol based on pBrO2 and ICP values.; Management protocol based on ICP values only.
Intervention description: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (> 20 mm Hg) or pBrO2 (< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.; For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Hypoxia; Ischemia; Intracranial hypertension; Neurocritical care

Summary:

      Traumatic brain injury (TBI) is a major cause of death and disability, with an estimated cost
      of 45 billion dollars a year in the United States alone. Every year, approximately 1.4
      million sustain a TBI, of which 50,000 people die, and another 235,000 are hospitalized and
      survive the injury. As a result, 80,000-90,000 people experience permanent disability
      associated with TBI. This project is designed to determine whether a device designed to
      measure brain tissue oxygenation and thus detect brain ischemia while it is still potentially
      treatable shows promise in reducing the duration of brain ischemia, and to obtain information
      required to conduct a definitive clinical trial of efficacy.

      A recently approved device makes it feasible to directly and continuously monitor the partial
      pressure of oxygen in brain tissue (pBrO2). Several observational studies indicate that
      episodes of low pBrO2 are common and are associated with a poor outcome, and that medical
      interventions are effective in improving pBrO2 in clinical practice. However, as there have
      been no randomized controlled trials carried out to determine whether pBrO2 monitoring
      results in improved outcome after severe TBI, use of this technology has not so far been
      widely adopted in neurosurgical intensive care units (ICUs). This study is the first
      randomized, controlled clinical trial of pBrO2 monitoring, and is designed to obtain data
      required for a definitive phase III study, such as efficacy of physiologic maneuvers aimed at
      treating pBrO2, and feasibility of standardizing a complex intensive care unit management
      protocol across multiple clinical sites.

      Patients with severe TBI will be monitored with Intracranial pressure monitoring (ICP) and
      pBrO2 monitoring, and will be randomized to therapy based on ICP along (control group) or
      therapy based on ICP in addition to pBrO2 values (treatment group). 182 participants will be
      enrolled at four clinical sites, the University of Texas Southwestern Medical Center/Parkland
      Memorial Hospital, the University of Washington/Harborview Medical Center, the University of
      Miami/Jackson Memorial Hospital, and the University of Pennsylvania/Hospital of the
      University of Pennsylvania. Functional outcome will be assessed at 6-months after injury.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Non-penetrating traumatic brain injury

          2. Requirement for intracranial pressure monitoring according to Guidelines for the
             Management of Severe TBI, as operationalized below:

               -  GCS 3-8 (measured off sedatives or paralytics) with abnormal CT scan. If patient
                  is intubated, motor GCS < 4 required.

               -  If CT scan normal, motor GCS < 4 (measured off sedatives or paralytics)

               -  Intoxication is not a reason for deferring ICP monitoring if above criteria are
                  met.

               -  If the patient has a witnessed seizure, wait 30 minutes to evaluate GCS.

          3. Randomization and placement of monitors within 12 hours of injury.

          4. Males and females Age 18-70 years, English or Spanish speaking patients.

        Exclusion Criteria:

          1. Specific clinical contraindications:

               -  GCS motor score > 4 with normal CT scan

               -  Bilaterally absent pupillary responses

          2. Laboratory contraindications per safety considerations:

             Coagulopathy that makes insertion of parenchymal monitors contraindicated (Platelets <
             50,000/mL, INR > 1.4) (Enrollment allowed if coagulopathy can be corrected before 12
             hour post-injury deadline).

          3. Pregnant females will be excluded. Blood test for pregnancy is a routine part of care
             in ED's. However, if not done, a urine or blood test will be done as a safety
             precaution after consent but prior to study treatment.

          4. Monitoring with pBrO2 monitor prior to randomization.

          5. Clinical, demographic and other characteristics that precludes appropriate diagnosis,
             treatment or follow-up in the trial.

               -  Systemic sepsis at the time of screening

               -  Refractory hypotension (SBP < 70 mm Hg for > 30 minutes)

               -  Refractory systemic hypoxia (paO2 < 60 mm Hg on FiO2 < 0.5)

               -  Evidence of premorbid disabling conditions that interfere with outcome
                  assessment. These include diagnosis of Alzheimer's disease, Parkinson's disease,
                  multiple sclerosis, spinal cord injury with deficits, history of stroke, brain
                  tumors, chronic use of medication for disabling neurologic or psychiatric
                  disorder, or history of suicide attempt within the past year.

               -  Imminent death or current life-threatening disease

               -  Prisoner

               -  Individuals who hold religious beliefs against blood transfusion

               -  Previous TBI hospitalization greater than 1 day

               -  Patients who are unlikely to be available for follow-up interview, even by
                  telephone. for example, patients who are homeless, illegal aliens, or live in
                  foreign countries and those with whom future personal (including family) or
                  telephone contact is unlikely.

          6. Active drug or alcohol use or dependence that, in the opinion of the stie
             investigator, would interfere with follow-up.

          7. Imminent death or current life-threatening disease

          8. Inability or unwillingness of subject or legal guardian/representative to give written
             informed consent

          9. Participation in other observational or interventional clinical trials is allowed as
             long as the PI of each study agree ahead of time to allow co-enrollment.