Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (TBI)

NCT00974259 | Completed Phase 2 Results

• 2 other identifiers: R01NS061860R01NS061860-01A2
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Severe Traumatic Brain Injury

Keywords

Hypoxia; Ischemia; Intracranial hypertension; Neurocritical care

Outcome Measures

Primary Outcomes (1)

• Fraction of Time That Brain Oxygen Levels Are Below the Critical Threshold of 20 mm Hg .

  Proportion of time PbtO2 below 20 mm Hg

  5 days

Secondary Outcomes (3)

• Total Number Participants With Adverse Events Associated With PbtO2 Monitoring.

  5 days

• Adherence to PbtO2 and ICP-directed Treatment Protocol

  5 days

• Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.

  6 months

Study Arms (2)

pBrO2 and ICP management

EXPERIMENTAL

Treatment protocol based on pBrO2 and ICP values.

Device: Management protocol based on pBrO2 and ICP values.

ICP management

ACTIVE COMPARATOR

Treatment protocol based on ICP values only.

Device: Management protocol based on ICP values only.

Interventions

Management protocol based on pBrO2 and ICP values. DEVICE

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.

Also known as: Licox, Camino

pBrO2 and ICP management

Management protocol based on ICP values only. DEVICE

For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.

Also known as: Camino

ICP management

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• Randomization and placement of monitors within 12 hours of injury.
• Males and females Age 18-70 years, English or Spanish speaking patients.

You may not qualify if:

• Specific clinical contraindications:
• GCS motor score \> 4 with normal CT scan
• Bilaterally absent pupillary responses
• 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).
• 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 \< 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• University of Washington: collaborator
• University of Miami: collaborator
• University of Pittsburgh: collaborator
• Duke University: collaborator
• Ohio State University: collaborator
• Temple University: collaborator
• Thomas Jefferson University: collaborator
• University of Cincinnati: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (10)

University of Miami/Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, United States

Location

Ohio State University

Columbus, Ohio, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University

Philadelphia, Pennsylvania, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Washington/Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Okonkwo DO, Shutter LA, Moore C, Temkin NR, Puccio AM, Madden CJ, Andaluz N, Chesnut RM, Bullock MR, Grant GA, McGregor J, Weaver M, Jallo J, LeRoux PD, Moberg D, Barber J, Lazaridis C, Diaz-Arrastia RR. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017 Nov;45(11):1907-1914. doi: 10.1097/CCM.0000000000002619.

  PMID: 29028696 RESULT

MeSH Terms

Conditions

Brain Injuries, Traumatic; Hypoxia; Ischemia; Intracranial Hypertension

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Results Point of Contact

• Title: Ramon Diaz-Arrastia
• Organization: University of Pennsylvania

Ramon.Diaz-Arrastia@uphs.upenn.edu

215-662-9732

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: September 4, 2009
• First Posted: September 10, 2009
• Study Start: October 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 26, 2019
• Results First Posted: September 26, 2019

Record last verified: 2019-09

Locations

US (10)