Brain Oxygen Optimization in Severe TBI, Phase 3

Brain Injuries, Traumatic Clinical Trial

— BOOST3  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03754114
• Other study ID #: BOOST3
• Secondary ID: U01NS099046
• Status: Recruiting
• Phase: N/A
• Start date: August 28, 2019
• Est. completion date: November 1, 2027

Study information

• Verified date: December 2023
• Source: University of Michigan
• Contact: William Barsan, MD
• Phone: 734-232-2141
• Email: wbarsan[@]umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1094
• Est. completion date: November 1, 2027
• Est. primary completion date: November 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	CIUSSS-NIM Hopital du Sacre - Coeur de Montreal	Montréal
Canada	St. Michaels Hospital	Toronto	Ontario
United States	University of New Mexico Hospital	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Kings County Hospital Center	Brooklyn	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	University of North Carolina Medical Center	Chapel Hill	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Parkland Hospital	Dallas	Texas
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Hospital	Durham	North Carolina
United States	UF Health Shands Hospital	Gainesville	Florida
United States	Ben Taub General Hospital	Houston	Texas
United States	Memorial Hermann Hospital	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	WVU Healthcare Ruby Memorial Hospital	Morgantown	West Virginia
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	NYP Columbia University Medical Center	New York	New York
United States	Stanford University Medical Center	Palo Alto	California
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	Maine Medical Center	Portland	Maine
United States	Oregon Health & Science University Hospital	Portland	Oregon
United States	VCU Medical Center	Richmond	Virginia
United States	Strong Memorial Hospital	Rochester	New York
United States	UC Davis Medical Center	Sacramento	California
United States	Regions Hospital	Saint Paul	Minnesota
United States	University of Utah Healthcare	Salt Lake City	Utah
United States	University of Texas Health Science Center San Antonio	San Antonio	Texas
United States	San Francisco General Hospital	San Francisco	California
United States	Harborview Medical Center	Seattle	Washington
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (6)

Lead Sponsor	Collaborator
University of Michigan	Medical University of South Carolina, National Institute of Neurological Disorders and Stroke (NINDS), University of Pennsylvania, University of Pittsburgh, University of Washington

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Survival	Survival at discharge from hospital	At discharge from hospital, an average of 19 days
Secondary	Total Brain Hypoxia Exposure	The cumulative area on the time versus brain tissue oxygenation (PbtO2) curve in which PbtO2 is less than 20 mmHg.	Inclusive of up to 5 days of study intervention
Secondary	Cognition: Rey Auditory Verbal Learning Test	A measure of verbal learning and memory.	6 months
Secondary	Cognition: Trail Making Test Part A+B	A measure of attention, visual-motor tracking and executive functioning.	6 months
Secondary	Emotional Health: Rivermead Post-Concussion Symptom Questionnaire	A measure of the presence and severity of post-concussion somatic, cognitive, and emotional symptoms.	6 months
Secondary	Emotional Health: Brief Symptom Inventory 18	A measure of psychological distress and psychiatric disorders.	6 months
Secondary	Emotional Health: Satisfaction with Life Scale	A measure of global cognitive judgments of one's life satisfaction.	6 months
Secondary	Functional Status Exam	Change in the activities of every day life as a function of a sudden event or illness	6 months

External Links

•   BOOST3 Study Website