Advanced Monitoring Strategy for Severe Traumatic Brain Injury

(BOOST3 Trial)

Recruiting at 45 trial locations

Overseen By Wendy Chang

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Disqualifiers: Non-survivable injury, Sepsis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

1094 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for severe traumatic brain injury?

Research shows that using brain tissue oxygen monitoring (PbtO2) along with intracranial pressure (ICP) management can improve survival rates and reduce pressure in the brain for patients with severe traumatic brain injury, although it may not significantly improve neurological outcomes. ^{1 2 3 4 5}

Is the advanced monitoring strategy for severe traumatic brain injury safe for humans?

The advanced monitoring strategy, which includes brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring, has been studied in patients with traumatic brain injury and is associated with improved survival and reduced mortality without significant differences in adverse respiratory or cardiovascular events. However, the certainty of the evidence is low, indicating a need for further research to confirm these findings. ^{2 3 5 6 7}

How does the ICP + PbtO2 guided management treatment for severe traumatic brain injury differ from other treatments?

This treatment is unique because it combines monitoring of intracranial pressure (ICP) with brain tissue oxygen levels (PbtO2) to guide management, aiming to prevent secondary brain injuries and improve survival rates, whereas traditional methods focus only on ICP monitoring. ^{3 5 7 8 9}

Research Team

William Barsan, MD

Principal Investigator

University of Michigan, Ann Arbor, MI 48109

Ramon Diaz-Arrastia, MD, PhD

Principal Investigator

University of Pennsylvania, Philadelphia, PA 19104

Sharon Yeatts, PhD

Principal Investigator

Medical University of South Carolina, Charleston, SC 29425

Lori Shutter, MD

Principal Investigator

University of Pittsburgh, Pittsburgh, PA 15260

Eligibility Criteria

This trial is for individuals aged 14 or older with severe traumatic brain injury (TBI), evidenced by a low Glasgow Coma Scale score and CT scan showing intracranial trauma. They must be able to have monitoring probes placed within specific time frames post-injury. Excluded are pregnant women, prisoners, those with certain medical conditions like systemic sepsis, or pre-existing neurological deficits that could affect the study.

Inclusion Criteria

Your Glasgow Coma Scale (GCS) score is between 3 and 8 and was measured without using paralyzing drugs.

I have had a brain injury without an object going through my skull.

I can have brain probes placed within 6 hours of getting to the hospital.

Exclusion Criteria

You have an injury that cannot be survived.

I do not have an infection in my blood.

I needed help with daily activities before my injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive ICU care guided by either ICP monitoring alone or ICP + PbtO2 monitoring for the first 5 days after injury

5 days

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a follow-up interview to assess recovery approximately 6 months post-injury

6 months

Treatment Details

Interventions

• ICP guided management strategy
• ICP + PbtO2 guided management strategy

Trial Overview BOOST3 compares two TBI treatment strategies in the ICU: one using goals based on both intracranial pressure (ICP) and brain tissue oxygen levels (PbtO2), versus another using ICP alone. The study aims to find out which method is safer and more effective for adjusting treatments such as medication doses, IV fluids, ventilator settings, etc.

Participant Groups

Group I: ICP only Active Control 1 Intervention

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.

Group II: ICP + PbtO2 Active Control 1 Intervention

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.

ICP guided management strategy is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Intracranial Pressure Monitoring for:

• Traumatic Brain Injury

Approved in Canada as Intracranial Pressure Monitoring for:

• Traumatic Brain Injury

Approved in European Union as Intracranial Pressure Monitoring for:

• Traumatic Brain Injury

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Findings from Research

In a study of 52 children with severe traumatic brain injury (TBI), reduced brain tissue oxygen tension (PbtO(2)) was found to be a strong independent predictor of poor outcomes, with a particularly high risk when PbtO(2) levels were below 5 mmHg for more than one hour.

The study suggests that PbtO(2) monitoring may provide critical insights into patient outcomes that are not captured by traditional measures like intracranial pressure (ICP) and cerebral perfusion pressure (CPP), highlighting its potential importance in managing severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tissue oxygen tension monitoring in pediatric severe traumatic brain injury. Part 1: Relationship with outcome. Figaji, AA., Zwane, E., Thompson, C., et al.[2021]

In a study of 50 patients with moderate to severe traumatic brain injury, those treated with PbtO2-guided therapy showed significantly higher survival rates at 3 and 6 months compared to those receiving traditional ICP-guided treatment.

The results indicate that monitoring PbtO2 levels and maintaining them above 20 mmHg can improve neurological outcomes, suggesting that this approach may be more effective in preventing cerebral hypoxia after brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management in Moderate and Severe Traumatic Brain Injury Patients. Lin, CM., Lin, MC., Huang, SJ., et al.[2018]

PbtO2-guided management in severe traumatic brain injury did not significantly improve the proportion of patients with favorable neurological outcomes compared to ICP-guided management alone, indicating that while it may not enhance recovery, it does not worsen it.

However, PbtO2-guided management was associated with a significant reduction in mortality and intracranial pressure (ICP), suggesting potential benefits in survival without increasing the risk of adverse respiratory or cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis. Hays, LMC., Udy, A., Adamides, AA., et al.[2022]

Monitoring brain tissue oxygen (PbtO(2)) and using a PbtO(2)-directed critical care guide significantly improved brain oxygen levels and reduced mortality rates in patients with severe traumatic brain injury (TBI), with a 44% increase in mean PbtO(2) and a 37% reduction in mortality compared to standard ICP/CPP management.

Patients treated with the PbtO(2)-CCG showed better 6-month clinical outcomes, with a higher Glasgow Outcome Scale score (3.55 vs 2.71) and a greater likelihood of good outcomes, especially in those with diffuse brain injuries, indicating that aggressive management of cerebral oxygenation is crucial for recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen-directed therapy. Narotam, PK., Morrison, JF., Nathoo, N.[2022]

In a study of 46 patients with severe traumatic brain injury (TBI), those monitored with both intracranial pressure (ICP) and brain tissue oxygenation (PbtO2) showed a significantly lower mortality rate of 8.7% compared to 21.7% in those monitored with ICP alone.

Patients receiving combined ICP and PbtO2 monitoring also had a better recovery outcome, with 65.2% achieving favorable results on the Glasgow outcome scale, compared to 47.8% in the ICP-only group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Guiding value of brain tissue oxygenation plus intracranial pressure monitoring in severe traumatic brain injury patients]. Wang, QP., Zhang, SM., Gao, H., et al.[2013]

In a meta-analysis of 15 studies involving 37,245 patients, PbtO2-guided therapy significantly improved neurological outcomes and hospital survival rates compared to traditional ICP-guided therapy, with an odds ratio of 2.21 for favorable outcomes.

Despite the promising results, the overall quality of evidence was low to moderate, highlighting the need for further research through ongoing phase III randomized trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Invasive Brain Oxygen Pressure Guided Therapy on the Outcome of Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Gouvêa Bogossian, E., Diosdado, A., Barrit, S., et al.[2022]

This study involves 1094 patients with severe traumatic brain injury (TBI) to evaluate whether monitoring brain tissue oxygenation (PbtO2) alongside intracranial pressure (ICP) can prevent secondary brain injuries and improve functional outcomes.

Patients will be randomly assigned to receive treatment based on either ICP alone or both ICP and PbtO2, with outcomes assessed using the Glasgow Outcome Scale-Extended at 180 days, aiming to determine if the addition of PbtO2 monitoring leads to better recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Bernard, F., Barsan, W., Diaz-Arrastia, R., et al.[2023]

In a study of 74 patients with severe traumatic brain injuries, the addition of brain tissue oxygen monitoring (pBtO2) did not significantly improve survival rates or functional outcomes compared to traditional ICP/CPP monitoring.

Although patients monitored with pBtO2 had lower injury severity scores, this did not translate into better survival or discharge outcomes, indicating that the clinical benefits of pBtO2 monitoring remain uncertain and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Goal directed brain tissue oxygen monitoring versus conventional management in traumatic brain injury: an analysis of in hospital recovery. Green, JA., Pellegrini, DC., Vanderkolk, WE., et al.[2021]

In a study of 49 pediatric patients with severe traumatic brain injury (TBI), those monitored with both intracranial pressure (ICP) and brain tissue oxygen tension (PbtO2) had longer stays in the pediatric intensive care unit (PICU) compared to those monitored with ICP alone, indicating that while PbtO2 monitoring may provide additional insights, it does not necessarily lead to better functional outcomes as measured by the Glasgow Outcome Score-Extended (GOS-E).

The study found that increased episodes of cerebral hypoxia (PbtO2 < 15 mm Hg) were linked to longer hospital stays and worse functional outcomes, highlighting the importance of maintaining adequate brain oxygen levels in managing severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Invasive brain tissue oxygen and intracranial pressure (ICP) monitoring versus ICP-only monitoring in pediatric severe traumatic brain injury. Lang, SS., Kumar, NK., Zhao, C., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Brain tissue oxygen tension monitoring in pediatric severe traumatic brain injury. Part 1: Relationship with outcome. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management in Moderate and Severe Traumatic Brain Injury Patients. [2018]

3. Scotland pubmed.ncbi.nlm.nih.gov

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen-directed therapy. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Guiding value of brain tissue oxygenation plus intracranial pressure monitoring in severe traumatic brain injury patients]. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

The Impact of Invasive Brain Oxygen Pressure Guided Therapy on the Outcome of Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Goal directed brain tissue oxygen monitoring versus conventional management in traumatic brain injury: an analysis of in hospital recovery. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Invasive brain tissue oxygen and intracranial pressure (ICP) monitoring versus ICP-only monitoring in pediatric severe traumatic brain injury. [2022]