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Brain Oxygen Optimization in Severe TBI, Phase 3 (BOOST3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03754114
Recruitment Status : Recruiting
First Posted : November 27, 2018
Last Update Posted : February 10, 2022
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
University of Washington
University of Pennsylvania
University of Pittsburgh
Medical University of South Carolina
Information provided by (Responsible Party):
William Barsan, University of Michigan

Tracking Information
First Submitted Date  ICMJE November 16, 2018
First Posted Date  ICMJE November 27, 2018
Last Update Posted Date February 10, 2022
Actual Study Start Date  ICMJE August 28, 2019
Estimated Primary Completion Date July 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2022)
Glasgow Outcome Scale-Extended (GOS-E) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 22, 2018)
Glasgow Outcome Scale-Extended (GOS-E) [ Time Frame: 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2022)
  • Survival [ Time Frame: At discharge from hospital, an average of 19 days ]
    Survival at discharge from hospital
  • Total Brain Hypoxia Exposure [ Time Frame: 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 [ Time Frame: 6 months ]
    A measure of verbal learning and memory.
  • Cognition: Trail Making Test Part A+B [ Time Frame: 6 months ]
    A measure of attention, visual-motor tracking and executive functioning.
  • Emotional Health: Rivermead Post-Concussion Symptom Questionnaire [ Time Frame: 6 months ]
    A measure of the presence and severity of post-concussion somatic, cognitive, and emotional symptoms.
  • Emotional Health: Brief Symptom Inventory 18 [ Time Frame: 6 months ]
    A measure of psychological distress and psychiatric disorders.
  • Emotional Health: Satisfaction with Life Scale [ Time Frame: 6 months ]
    A measure of global cognitive judgments of one's life satisfaction.
  • Functional Status Exam [ Time Frame: 6 months ]
    Change in the activities of every day life as a function of a sudden event or illness
Original Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2018)
  • Survival [ Time Frame: At discharge from hospital, an average of 19 days ]
    Survival at discharge from hospital
  • Total Brain Hypoxia Exposure [ Time Frame: 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 [ Time Frame: 6 months ]
    A measure of verbal learning and memory.
  • Cognition: Trail Making Test Part A+B [ Time Frame: 6 months ]
    A measure of attention, visual-motor tracking and executive functioning.
  • Cognition: WAIS IV Processing Speed Index [ Time Frame: 6 months ]
    A measure of processing speed, attention and working memory.
  • Cognition: WRAT-4 Reading Subtest [ Time Frame: 6 months ]
    A measure of letter and word decoding,
  • Emotional Health: Rivermead Post-Concussion Symptom Questionnaire [ Time Frame: 6 months ]
    A measure of the presence and severity of post-concussion somatic, cognitive, and emotional symptoms.
  • Emotional Health: Brief Symptom Inventory 18 [ Time Frame: 6 months ]
    A measure of psychological distress and psychiatric disorders.
  • Emotional Health: Satisfaction with Life Scale [ Time Frame: 6 months ]
    A measure of global cognitive judgments of one's life satisfaction.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brain Oxygen Optimization in Severe TBI, Phase 3
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
The outcomes assessors will be blinded to the treatment assignment of the participant.
Primary Purpose: Treatment
Condition  ICMJE Brain Injuries, Traumatic
Intervention  ICMJE
  • Other: ICP + PbtO2 guided management strategy
    In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg and to avoid PbtO2 dropping below 20 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada for patients with severe TBI. The devices are used in standard care at hospitals participating in this research study. Doctors adjust their treatment choices to try to achieve these ICP and PbtO2 goals. 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. This management strategy is used to guide care for 5 days in this research study.
  • Other: ICP guided management strategy
    In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull, but PbtO2 is not used to guide care. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada, and are routinely used in patients with severe TBI. Doctors adjust their treatment choices to try to achieve this ICP goal. 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. This management strategy is used to guide care for 5 days in this research study.
Study Arms  ICMJE
  • Active Comparator: ICP only
    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.
    Intervention: Other: ICP guided management strategy
  • Active Comparator: ICP + PbtO2
    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.
    Intervention: Other: ICP + PbtO2 guided management strategy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 22, 2018)
1094
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2023
Estimated Primary Completion Date July 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 < 200
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 14 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: William Barsan, MD 734-232-2141 wbarsan@umich.edu
Contact: William J Meurer, MD 734-232-2141 wmeurer@umich.edu
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03754114
Other Study ID Numbers  ICMJE BOOST3
U01NS099046 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data will be stored in the NHLBI data repository after trial completion.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: 1 year after publication on main outcome results paper
Access Criteria: Data use agreement with the appropriate NHLBI repository
Responsible Party William Barsan, University of Michigan
Study Sponsor  ICMJE University of Michigan
Collaborators  ICMJE
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • University of Washington
  • University of Pennsylvania
  • University of Pittsburgh
  • Medical University of South Carolina
Investigators  ICMJE
Principal Investigator: Lori Shutter, MD University of Pittsburgh, Pittsburgh, PA 15260
Principal Investigator: Ramon Diaz-Arrastia, MD, PhD University of Pennsylvania, Philadelphia, PA 19104
Principal Investigator: William Barsan, MD University of Michigan, Ann Arbor, MI 48109
Principal Investigator: Sharon Yeatts, PhD Medical University of South Carolina, Charleston, SC 29425
PRS Account University of Michigan
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP