Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (TBI) (BOOST 2)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by University of Texas Southwestern Medical Center.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
University of Washington
University of Miami
University of Pennsylvania
University of Pittsburgh
Duke University
Ohio State University
Temple University
Thomas Jefferson University
University of Cincinnati
Information provided by (Responsible Party):
Ramon Diaz-Arrastia, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00974259
First received: September 4, 2009
Last updated: May 15, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Severe Traumatic Brain Injury
Device: Management protocol based on pBrO2 and ICP values.
Device: Management protocol based on ICP values only.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2, Randomized Clinical Trial of the Safety and Efficacy of Brain Tissue Oxygen Monitoring in the Management of Severe Traumatic Brain Injury.

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • The prescribed treatment protocol, based on pBrO2 monitoring, results in reduction of the fraction of time that brain oxygen levels are below the critical threshold of 20 mm Hg in patients with severe traumatic brain injury. [ Time Frame: 5 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety hypotheses: Adverse events associated with pBrO2 monitoring are rare. [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Feasibility hypotheses: Episodes of decreased pBrO2 can be identified and treatment protocol instituted comparably across 4 clinical sites, and protocol violations will be low (<10%) and uniform across different clinical sites. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Non-futility hypothesis: A relative risk of good outcome measured by the Glasgow Outcome Scale-Extended 6 months after injury of 2.0 is consistent with the results of this phase II study. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 182
Study Start Date: October 2009
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pBrO2 and ICP management
Treatment protocol based on pBrO2 and ICP values.
Device: Management protocol based on pBrO2 and ICP values.
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.
Other Names:
  • Licox
  • Camino
Active Comparator: ICP management
Treatment protocol based on ICP values only.
Device: Management protocol based on ICP values only.
For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
Other Name: Camino

Detailed Description:

Design and Outcomes

This study is a two-arm, single-blind, randomized, controlled, phase II, multi-center pilot trial of the efficacy of pBrO2 monitoring, and is designed to obtain data required for a definitive phase III study, such as efficacy of physiologic maneuvers aimed at normalizing pBrO2. 182 patients with severe TBI who require ICP monitoring will be recruited into this study at 4 clinical sites in the US (Univ. of Texas Southwestern/Parkland Memorial Hospital, Univ. of Washington/Harborview Medical Center, Univ. of Miami/Jackson Memorial Hospital, and Univ. of Pennsylvania/Hospital of the Univ. of Pennsylvania). All patients will have both ICP monitors and pBrO2 monitors inserted through the same burr hole. Half of the patients will be randomized to a treatment protocol based on both ICP and pBrO2 readings, while the control group will be randomized to a treatment protocol based only on ICP readings. The pBrO2monitors of the control arm will be masked, so that the treating physicians will be unaware of the pBrO2 information. Patients will have telephone follow-up interview to assess their level of recovery 6 months post injury, using the Glasgow Outcome Scale-Extended.

Interventions and Duration

Patients randomized to the control group will have pBrO2 implanted in a similar fashion as patients in the treatment group, but after calibration of the device, the display will be covered with opaque tape. Patients in the control will be treated with a protocol based on ICP measures only. Patients in the treatment group (both ICP and pBrO2 measures are visible) will be treated according to a protocol that incorporates both ICP and pBrO2 measures. The treatment protocols are based on current standards of care, but are described in detail to insure uniformity in treatments across the 4 study sites.

The probe will remain in place for a maximum or 5 days, until all values are normal for 48 hours, or sooner if a complication arises. If the patient has normal values, monitors will be removed after 48 hours.

Objectives

Primary Objective: The prescribed treatment protocol, based on pBrO2 monitoring, results in reduction of the fraction of time that brain oxygen levels are below the critical threshold of 20 mm Hg in patients with severe traumatic brain injury.

Secondary Objectives:

  • Safety hypotheses: Adverse events associated with pBrO2 monitoring are rare.
  • Feasibility hypotheses: Episodes of decreased pBrO2 can be identified and treatment protocol instituted comparably across 4 clinical sites, and protocol violations will be low (<10%) and uniform across different clinical sites.
  • Non-futility hypothesis: A relative risk of good outcome measured by the Glasgow Outcome Scale-Extended 6 months after injury of 2.0 is consistent with the results of this phase II study.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00974259

Contacts
Contact: Ramon R. Diaz-Arrastia, MD, PhD 301-295-5537 Ramon.Diaz-Arrastia@usuhs.edu
Contact: Carol B. Moore, MA, CCRC 301-295-6439 Carol.Moore@usuhs.edu

Locations
United States, Florida
University of Miami/Jackson Memorial Hospital Recruiting
Miami, Florida, United States, 33136
Contact: Ross Bullock, MD, PhD    305-243-4456    RBullock@med.miami.edu   
Contact: Christopher Gilbert    305-243-8044    cgilbert@med.miami.edu   
Principal Investigator: Ross Bullock, MD, PhD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Gerald Grant, MD    919-684-5013    gerald.grant@duke.edu   
Principal Investigator: Gerald Grant, MD         
United States, Ohio
University of Cincinnati Not yet recruiting
Cincinnati, Ohio, United States
Contact: Norberto Andaluz, MD       andalun@ucmail.uc.edu   
Principal Investigator: Norberto Andaluz, MD         
Ohio State University Recruiting
Columbus, Ohio, United States
Contact: John McGregor, MD       John.McGregor@ohumc.edu   
Principal Investigator: John McGregor, MD         
United States, Pennsylvania
Temple University Recruiting
Philadelphia, Pennsylvania, United States
Contact: Michael Weaver, MD       Michael.Weaver@tuhs.temple.edu   
Principal Investigator: Michael Weaver, MD         
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States
Contact: Jack Jallo, MD       Jack.Jallo@jefferson.edu   
Principal Investigator: Jack Jallo, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Peter Le Roux, MD    215-829-7072    Peter.LeRoux@uphs.upenn.edu   
Contact: Suzanne Frangos, RN, CNRN    215-825-8585    frangoss@uphs.upenn.edu   
Principal Investigator: Peter Le Roux, MD         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States
Contact: David Okonknwo, MD, PhD       okonkwodo@upmc.edu   
Contact: Ava Puccio, PhD       PuccAM@UPMC.edu   
Principal Investigator: David Okonkwo, MD, PhD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Christopher Madden, MD    214-648-7905    Christopher.Madden@UTSouthwestern.edu   
Contact: Caryn Harper, MS    214-648-7613    Caryn.Harper@UTSouthwestern.edu   
Principal Investigator: Christopher Madden, MD         
United States, Washington
University of Washington/Harborview Medical Center Recruiting
Seattle, Washington, United States, 98104
Contact: Randall M. Chesnut, MD    206-744-9374    ChesnutR@u.washington.edu   
Contact: Anna Roueche, RN    206-744-9364    annarn@u.washington.edu   
Principal Investigator: Randall M. Chesnut, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
University of Washington
University of Miami
University of Pennsylvania
University of Pittsburgh
Duke University
Ohio State University
Temple University
Thomas Jefferson University
University of Cincinnati
  More Information

No publications provided

Responsible Party: Ramon Diaz-Arrastia, Professor of Neurology, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00974259     History of Changes
Other Study ID Numbers: R01 NS061860, R01 NS061860
Study First Received: September 4, 2009
Last Updated: May 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
Hypoxia
Ischemia
Intracranial hypertension
Neurocritical care

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on October 23, 2014