NCT03754114

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.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,094

participants targeted

Target at P75+ for not_applicable

Timeline
19mo left

Started Aug 2019

Longer than P75 for not_applicable

Geographic Reach
2 countries

51 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress82%
Aug 2019Nov 2027

First Submitted

Initial submission to the registry

November 16, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

November 27, 2018

Completed
9 months until next milestone

Study Start

First participant enrolled

August 28, 2019

Completed
8.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2027

Last Updated

May 5, 2026

Status Verified

April 1, 2026

Enrollment Period

8.2 years

First QC Date

November 16, 2018

Last Update Submit

April 30, 2026

Conditions

Keywords

intracranial pressurehypoxia, braincritical careemergency treatmentmonitoring, physiologic

Outcome Measures

Primary Outcomes (1)

  • Glasgow Outcome Scale-Extended (GOS-E)

    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.

    6 months

Secondary Outcomes (8)

  • Survival

    At discharge from hospital, an average of 19 days

  • Total Brain Hypoxia Exposure

    Inclusive of up to 5 days of study intervention

  • Cognition: Rey Auditory Verbal Learning Test

    6 months

  • Cognition: Trail Making Test Part A+B

    6 months

  • Emotional Health: Rivermead Post-Concussion Symptom Questionnaire

    6 months

  • +3 more secondary outcomes

Study Arms (2)

ICP only

ACTIVE COMPARATOR

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

ICP + PbtO2

ACTIVE COMPARATOR

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

Interventions

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.

ICP + PbtO2

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.

ICP only

Eligibility Criteria

Age14 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (51)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095-7436, United States

Location

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

San Francisco General Hospital

San Francisco, California, 94143, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32608, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

The Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

St. Vincent Hospital

Indianapolis, Indiana, 46260, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02128, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

UMASS Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48201, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

University of New Mexico Hospital

Albuquerque, New Mexico, 87131, United States

Location

NewYork-Presbyterian Queens Hospital

Flushing, New York, 11355, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

NYP Columbia University Medical Center

New York, New York, 10032, United States

Location

Strong Memorial Hospital

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Oregon Health & Science University Hospital

Portland, Oregon, 97239, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Parkland Hospital

Dallas, Texas, 75235, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah Healthcare

Salt Lake City, Utah, 84132, United States

Location

VCU Medical Center

Richmond, Virginia, 23298, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

WVU Healthcare Ruby Memorial Hospital

Morgantown, West Virginia, 26506, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

University of Calgary - Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

St. Michaels Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

CIUSSS-NIM Hopital du Sacre - Coeur de Montreal

Montreal, H4J 1C5, Canada

Location

Related Publications (3)

  • 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: 29028696BACKGROUND
  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Brain Injuries, TraumaticHypoxia, Brain

Condition Hierarchy (Ancestors)

Brain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and InjuriesHypoxiaSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
The outcomes assessors will be blinded to the treatment assignment of the participant.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Emergency Medicine

Study Record Dates

First Submitted

November 16, 2018

First Posted

November 27, 2018

Study Start

August 28, 2019

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

November 1, 2027

Last Updated

May 5, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share
Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
1 year after publication on main outcome results paper

Locations