Clinical trial NCT03754114: Brain Oxygen Optimization in Severe TBI, Phase 3
Official title: Brain Oxygen Optimization in Severe TBI (BOOST3): a Comparative Effectiveness Study to Test the Efficacy of a Prescribed Treatment Protocol Based on Monitoring the Partial Pressure of Brain Tissue Oxygen.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Brain Injuries, Traumatic
Keywords: intracranial pressure
hypoxia, brain
critical care
emergency treatment
monitoring, physiologic
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Washington
name: University of Pennsylvania
name: University of Pittsburgh
name: Medical University of South Carolina
First posted: 2018-11-27
Enrollment: 1094
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Glasgow Outcome Scale-Extended (GOS-E)
timeFrame: 6 months
Secondary outcomes:
measure: Survival
timeFrame: At discharge from hospital, an average of 19 days
measure: Total Brain Hypoxia Exposure
timeFrame: Inclusive of up to 5 days of study intervention
measure: Cognition: Rey Auditory Verbal Learning Test
timeFrame: 6 months
measure: Cognition: Trail Making Test Part A+B
timeFrame: 6 months
measure: Emotional Health: Rivermead Post-Concussion Symptom Questionnaire
timeFrame: 6 months
measure: Emotional Health: Brief Symptom Inventory 18
timeFrame: 6 months
measure: Emotional Health: Satisfaction with Life Scale
timeFrame: 6 months
measure: Functional Status Exam
timeFrame: 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington, DC
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Hospital
state: New Mexico
city: Brooklyn
country: United States
facility: Kings County Hospital Center
state: New York
city: ManHASSET
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYP Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Parkland Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Healthcare
state: Utah
city: Richmond
country: United States
facility: VCU Medical Center
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Morgantown
country: United States
facility: WVU Healthcare Ruby Memorial Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary - Foothills Medical Centre
state: Alberta
city: Toronto
country: Canada
facility: St. Michaels Hospital
state: Ontario
city: Montréal
country: Canada
facility: CIUSSS-NIM Hopital du Sacre - Coeur de Montreal
Study officials:
affiliation: University of Pittsburgh, Pittsburgh, PA 15260
name: Lori Shutter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania, Philadelphia, PA 19104
name: Ramon Diaz-Arrastia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan, Ann Arbor, MI 48109
name: William Barsan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina, Charleston, SC 29425
name: Sharon Yeatts, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Bernard F, Barsan W, Diaz-Arrastia R, Merck LH, Yeatts S, Shutter LA. Brain Oxygen Optimization in Severe Traumatic Brain Injury (BOOST-3): a multicentre, randomised, blinded-endpoint, comparative effectiveness study of brain tissue oxygen and intracranial pressure monitoring versus intracranial pressure alone. BMJ Open. 2022 Mar 10;12(3):e060188. doi: 10.1136/bmjopen-2021-060188.
citation: Fiore M, Bogossian E, Creteur J, Oddo M, Taccone FS. Role of brain tissue oxygenation (PbtO2) in the management of subarachnoid haemorrhage: a scoping review protocol. BMJ Open. 2020 Sep 15;10(9):e035521. doi: 10.1136/bmjopen-2019-035521.