Phase 2
N=122
Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (TBI)
Severe Traumatic Brain Injury
Bottom Line
View on ClinicalTrials.gov: NCT00974259 ↗Enrolled (actual)
122
Serious AEs
51.3%
Results posted
Sep 2019
Primary outcome: Primary: Fraction of Time That Brain Oxygen Levels Are Below the Critical Threshold of 20 mm Hg . — 0.15; 0.44 Proportion
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Management protocol based on pBrO2 and ICP values. (Device); Management protocol based on ICP values only. (Device)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Pennsylvania
- Primary completion
- Mar 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Fraction of Time That Brain Oxygen Levels Are Below the Critical Threshold of 20 mm Hg . |
0.15; 0.44 | — |
| SECONDARY Total Number Participants With Adverse Events Associated With PbtO2 Monitoring. |
9; 8; 1; 1; 5; 10 | — |
| SECONDARY Adherence to PbtO2 and ICP-directed Treatment Protocol |
95; 71; 24; 0; 7; 14 | — |
| SECONDARY Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group. |
13; 18; 1; 2; 7; 5 | — |
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
- Non-penetrating traumatic brain injury
- 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 with normal CT scan
- Bilaterally absent pupillary responses
- Laboratory contraindications per safety considerations:
Coagulopathy that makes insertion of parenchymal monitors contraindicated (Platelets 1.4) (Enrollment allowed if coagulopathy can be corrected before 12 hour post-injury deadline).
- 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.
- Monitoring with pBrO2 monitor prior to randomization.
- 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 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.
- Active drug or alcohol use or dependence that, in the opinion of the stie investigator, would interfere with follow-up.
- Imminent death or current life-threatening disease
- Inability or unwillingness of subject or legal guardian/representative to give written informed consent
- 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.
Data sourced from ClinicalTrials.gov (NCT00974259). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.