Brain Oxygen Optimization in Severe TBI, Phase 3
- Conditions
- Brain Injuries, Traumatic
- Interventions
- Other: ICP + PbtO2 guided management strategyOther: ICP guided management strategy
- Registration Number
- NCT03754114
- Lead Sponsor
- University of Michigan
- Brief Summary
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two strategies for monitoring and treating patients with traumatic brain injury (TBI) in the intensive care unit (ICU). The study will determine the safety and efficacy of a strategy guided by treatment goals based on both intracranial pressure (ICP) and brain tissue oxygen (PbtO2) as compared to a strategy guided by treatment goals based on ICP monitoring alone. Both of these alternative strategies are used in standard care. It is unknown if one is more effective than the other. In both strategies the monitoring and goals help doctors adjust treatments including the kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. The results of this study will help doctors discover if one of these methods is more safe and effective.
- Detailed Description
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two strategies for monitoring and treating patients with traumatic brain injury (TBI) in the intensive care unit (ICU).
When a person has a TBI, their injured brain can swell over a period of hours or days. If the brain swells too much, the pressure in the skull increases and becomes dangerous, causing further injury to the brain. To try to prevent this, doctors usually insert a device, an ICP monitor, into the brain through a hole in the skull of people with severe TBI. An ICP monitor measures the pressure inside the skull. Most doctors agree that it is important to measure and prevent high ICP. Patients with injured brains also suffer additional injury to the brain if the amount of oxygen in the brain gets too low. Some doctors also insert a second device, a PbtO2 monitor, in the brain through the same or a second hole in the skull to measure brain tissue oxygen. A PbtO2 monitor measures how much oxygen is in a small area of the brain near the tip of the monitor. Other doctors think this is unnecessary and unhelpful. Both monitoring devices are approved by the US Food and Drug Administration (FDA) and Health Canada for patients with TBI. Both are commonly used. The ICP and PbtO2 goals guided by these monitors are used to help doctors adjust their treatment choices. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. Each of these treatment decisions is intended to improve outcomes. However, each treatment decision also involves potential risks. Different treatment decisions may result in different risks. This study will also help doctors better understand these risks. This study is funded by the National Institutes of Health because it answers questions important to the care of patients with TBI.
This study is a two-arm, single-blind, randomized, controlled, phase III, multi-center trial of ICU monitoring and treatment strategies for patients with severe TBI. It will compare the efficacy of ICU care guided by PbtO2 and ICP monitoring versus monitoring of ICP alone in the first 5 days after injury. Only subjects who have severe TBI and require invasive monitoring, according to Brain Trauma Foundation (BTF) and American College of Surgeons-Trauma Quality Improvement (ACS TQIP) guidelines, will be enrolled. All participants in this study will have both ICP monitors and PbtO2 monitors. Half of the participants will be randomized to an arm that includes treatment informed by PbtO2 and ICP, and half will be randomized to an arm that treats only ICP.
The PbtO2 values of those in the ICP only arm will be masked, so that the treating physicians will not be guided by PbtO2 information. Participants in the PbtO2 and ICP arm will have PbtO2 monitored and low measurements treated. Treatments to address physiological goals in both arms will follow a clinical standardization plan. Participants will be followed for 6 months and occurrence of serious adverse events or death will be recorded. Participants will have a follow-up interview to assess their level of recovery approximately 6 months post injury.
To reduce the likelihood of imbalance of important prognostic factors between groups, a covariate-adjusted randomization scheme will be used in this study. Adjustment variables are clinical site and probability of a poor outcome as defined by the IMPACT core model.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1094
- Non-penetrating traumatic brain injury
- Glasgow Coma Scale (GCS) 3-8 measured off paralytics
- Glasgow Coma Scale motor score < 6 if endotracheally intubated
- Evidence of intracranial trauma on CT scan
- Able to place intracranial probes and randomize within 6 hours of arrival at enrolling hospital
- Able to place intracranial probes and randomize within 12 hours from injury
- Age greater than or equal to 14 years
- Non-survivable injury
- Bilaterally absent pupillary response in the absence of paralytic medication
- Contraindication to the placement of intracranial probes
- Treatment of brain tissue oxygen values prior to randomization
- Planned use of devices which may unblind treating physicians to brain tissue hypoxia
- Systemic sepsis at screening
- Refractory hypotension
- Refractory systemic hypoxia
- PaO2/FiO2 ratio < 150
- Known pre-existing neurologic disease with confounding residual neurological deficits
- Known inability to perform activities of daily living (ADL) without assistance prior to injury
- Known active drug or alcohol dependence that, in the opinion of site investigator, would interfere with physiological response to brain tissue oxygen treatments
- Pregnancy
- Prisoner
- On EFIC Opt-Out list as indicated by a bracelet or medical alert
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ICP + PbtO2 ICP + PbtO2 guided management strategy ICP + PbtO2 guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP), and also try to prevent low PbtO2 (brain tissue oxygen levels). This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury. ICP only ICP guided management strategy ICP guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP) caused by a swollen brain. This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury.
- Primary Outcome Measures
Name Time Method Glasgow Outcome Scale-Extended (GOS-E) 6 months The Glasgow Outcome Scale-Extended (GOS-E) is a global scale for functional outcome, in which higher scores indicate better outcomes. The GOS-E rates patient status into one of eight categories. A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. All injury related disabilities are assessed.
- Secondary Outcome Measures
Name Time Method Survival At discharge from hospital, an average of 19 days Survival at discharge from hospital
Emotional Health: Brief Symptom Inventory 18 6 months A measure of psychological distress and psychiatric disorders.
Functional Status Exam 6 months Change in the activities of every day life as a function of a sudden event or illness
Total Brain Hypoxia Exposure Inclusive of up to 5 days of study intervention The cumulative area on the time versus brain tissue oxygenation (PbtO2) curve in which PbtO2 is less than 20 mmHg.
Cognition: Rey Auditory Verbal Learning Test 6 months A measure of verbal learning and memory.
Emotional Health: Rivermead Post-Concussion Symptom Questionnaire 6 months A measure of the presence and severity of post-concussion somatic, cognitive, and emotional symptoms.
Cognition: Trail Making Test Part A+B 6 months A measure of attention, visual-motor tracking and executive functioning.
Emotional Health: Satisfaction with Life Scale 6 months A measure of global cognitive judgments of one's life satisfaction.
Trial Locations
- Locations (48)
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
University of Calgary - Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
San Francisco General Hospital
🇺🇸San Francisco, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
MedStar Washington Hospital Center
🇺🇸Washington, DC, District of Columbia, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
UMASS Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Cooper University Hospital
🇺🇸Camden, New Jersey, United States
University of New Mexico Hospital
🇺🇸Albuquerque, New Mexico, United States
Kings County Hospital Center
🇺🇸Brooklyn, New York, United States
North Shore University Hospital
🇺🇸ManHASSET, New York, United States
NYP Columbia University Medical Center
🇺🇸New York, New York, United States
Strong Memorial Hospital
🇺🇸Rochester, New York, United States
University of North Carolina Medical Center
🇺🇸Chapel Hill, North Carolina, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
OSU Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Oregon Health & Science University Hospital
🇺🇸Portland, Oregon, United States
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Parkland Hospital
🇺🇸Dallas, Texas, United States
Memorial Hermann Hospital
🇺🇸Houston, Texas, United States
Ben Taub General Hospital
🇺🇸Houston, Texas, United States
University of Texas Health Science Center San Antonio
🇺🇸San Antonio, Texas, United States
University of Utah Healthcare
🇺🇸Salt Lake City, Utah, United States
VCU Medical Center
🇺🇸Richmond, Virginia, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
WVU Healthcare Ruby Memorial Hospital
🇺🇸Morgantown, West Virginia, United States
Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
St. Michaels Hospital
🇨🇦Toronto, Ontario, Canada
CIUSSS-NIM Hopital du Sacre - Coeur de Montreal
🇨🇦Montréal, Canada