Brain Oxygen Optimization in Severe TBI, Phase 3

Purpose

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.

Condition

  • Brain Injuries, Traumatic

Eligibility

Eligible Ages
Over 14 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)
Masking Description
The outcomes assessors will be blinded to the treatment assignment of the participant.

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • 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.
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.
  • 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.

Recruiting Locations

Cedars-Sinai Medical Center
Los Angeles 5368361, California 5332921 90048
Contact:
Maranatha Ayodele

Stanford University Medical Center
Palo Alto 5380748, California 5332921 94305
Contact:
Karen Hirsch

UC Davis Medical Center
Sacramento 5389489, California 5332921 95817
Contact:
Lara Zimmermann, MD

Yale New Haven Hospital
New Haven 4839366, Connecticut 4831725 06510
Contact:
Emily Gilmore, MD

UF Health Shands Hospital
Gainesville 4156404, Florida 4155751 32608
Contact:
Christopher Robinson

Grady Memorial Hospital
Atlanta 4180439, Georgia 4197000 30303
Contact:
Jonathan Ratcliff, MD

University of Chicago Medical Center
Chicago 4887398, Illinois 4896861 60637
Contact:
Christos Lazaridis, MD

St. Vincent Hospital
Indianapolis 4259418, Indiana 4921868 46260
Contact:
Richard Rodgers, MD

Maine Medical Center
Portland 4975802, Maine 4971068 04102
Contact:
Teresa May, MD

Johns Hopkins Hospital
Baltimore 4347778, Maryland 4361885 21287
Contact:
Ruben Troncoso Jr, MPH, MD
855-662-3017
rubent@jhmi.edu

Brigham and Women's Hospital
Boston 4930956, Massachusetts 6254926 02115
Contact:
Bradley Molyneaux, MD, PhD

UMASS Memorial Medical Center
Worcester 4956184, Massachusetts 6254926 01655
Contact:
Raphael Carandang

University of Michigan
Ann Arbor 4984247, Michigan 5001836 48109
Contact:
Venkatakrishna Rajajee

Detroit Receiving Hospital
Detroit 4990729, Michigan 5001836 48201
Contact:
Wazim Mohamed, MD

Henry Ford Hospital
Detroit 4990729, Michigan 5001836 48201
Contact:
Christopher Lewandowski, MD

Cooper University Hospital
Camden 4501018, New Jersey 5101760 08103
Contact:
Alan Turtz, MD

University of New Mexico Hospital
Albuquerque 5454711, New Mexico 5481136 87131
Contact:
Huy Tran, MD

North Shore University Hospital
Manhasset 5125766, New York 5128638 11030
Contact:
Tania Rebeiz

Strong Memorial Hospital
Rochester 5134086, New York 5128638 14642
Contact:
David A. Paul, MD MS
888-661-6162
David_Paul@URMC.Rochester.edu

SUNY Upstate Medical University
Syracuse 5140405, New York 5128638 13210
Contact:
Devin J. Burke, MD
877 464-5540
BURKEDE@upstate.edu

Jacobi Medical Center
The Bronx 5110266, New York 5128638 10461
Contact:
Nrupen Baxi, MD

University of North Carolina Medical Center
Chapel Hill 4460162, North Carolina 4482348 27514
Contact:
Matthew Sharrock

Duke University Hospital
Durham 4464368, North Carolina 4482348 27710
Contact:
Katharine Colton, MD

University of Cincinnati Medical Center
Cincinnati 4508722, Ohio 5165418 45219
Contact:
Natalie Kreitzer

OSU Wexner Medical Center
Columbus 4509177, Ohio 5165418 43210
Contact:
Mhdezzat Zaghlouleh, MD

Oregon Health & Science University Hospital
Portland 5746545, Oregon 5744337 97239
Contact:
James M. Wright III, MD
503-494-8311
wrighjam@ohsu.edu

Penn Presbyterian Medical Center
Philadelphia 4560349, Pennsylvania 6254927 19104
Contact:
Danielle Sandsmark

Thomas Jefferson University Hospital
Philadelphia 4560349, Pennsylvania 6254927 19107
Contact:
Jack Jallo, MD

UPMC Presbyterian Hospital
Pittsburgh 5206379, Pennsylvania 6254927 15212
Contact:
David Okonkwo, MD

Parkland Hospital
Dallas 4684888, Texas 4736286 75235
Contact:
Stephen Figueroa

Ben Taub General Hospital
Houston 4699066, Texas 4736286 77030
Contact:
Jovany Cruz, MD

University of Texas Health Science Center San Antonio
San Antonio 4726206, Texas 4736286 78229
Contact:
Michael McGinity

University of Utah Healthcare
Salt Lake City 5780993, Utah 5549030 84132
Contact:
Holly Ledyard

Inova Fairfax Hospital
Falls Church 4758390, Virginia 6254928 22042
Contact:
Ramani Balu, MD

VCU Medical Center
Richmond 4781708, Virginia 6254928 23298
Contact:
Lisa Merck

Harborview Medical Center
Seattle 5809844, Washington 5815135 98104
Contact:
Randall Chesnut

Froedtert Hospital
Milwaukee 5263045, Wisconsin 5279468 53226
Contact:
Gregory Rozansky

More Details

NCT ID
NCT03754114
Status
Recruiting
Sponsor
University of Michigan

Study Contact

William Barsan, MD
734-232-2141
wbarsan@umich.edu

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.

For help using this page: trialstoday@researchmatch.org or call 855-514-7001

ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center