Advanced Monitoring Strategy for Severe Traumatic Brain Injury

(BOOST3 Trial)

Recruiting at 46 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to monitor and treat individuals with severe traumatic brain injuries in the ICU. It compares two strategies: one monitors only intracranial pressure (ICP guided management strategy), while the other monitors both intracranial pressure and brain oxygen levels (ICP + PbtO2 guided management strategy). Hospitals already use both methods, but their relative safety and effectiveness remain unclear. Suitable candidates have experienced a traumatic brain injury, are in a coma, and have a recent CT scan showing brain damage. As an unphased trial, this study allows participants to contribute to important research that could enhance ICU care for future patients with traumatic brain injuries.

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 prior data suggests that these monitoring strategies are safe for patients with traumatic brain injury?

A previous study on intracranial pressure (ICP) monitoring in patients with severe head injuries showed mixed results. Some studies have found that ICP monitoring lowers the risk of death, while others suggested it might worsen recovery and survival outcomes. These mixed findings highlight the ongoing debate about the effectiveness of ICP monitoring.

Research indicates that adding brain tissue oxygen (PbtO2) monitoring to ICP monitoring does not always lead to better results. Some studies found that this combined approach did not improve recovery outcomes after six months. However, another study showed that it could help reduce low oxygen levels in the brain, which might be beneficial.

Both monitoring methods are currently used in standard care, with doctors regularly employing them to treat patients with severe brain injuries. The current study aims to determine if one method is better or safer than the other. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores new ways to monitor and manage severe traumatic brain injury (TBI) in the ICU. Unlike standard care that focuses solely on preventing high intracranial pressure (ICP), this trial introduces an advanced method that also monitors brain tissue oxygen levels (PbtO2). By adding the PbtO2 monitoring, doctors can potentially prevent not just pressure issues, but also low oxygen levels in the brain, which could lead to better outcomes for patients. This dual approach could offer a more comprehensive and effective management strategy for TBI patients, sparking hope for improved recovery rates.

What evidence suggests that this trial's monitoring strategies could be effective for traumatic brain injury?

Research has shown that monitoring intracranial pressure (ICP) can reduce death rates in individuals with severe head injuries. In this trial, participants in the "ICP only" arm will have their care guided solely by ICP monitoring. Patients with monitored ICP often experience better outcomes and may have extended ICU stays, potentially enhancing recovery chances.

Participants in the "ICP + PbtO2" arm will have their care guided by monitoring both intracranial pressure and brain tissue oxygen levels. Monitoring brain tissue oxygen levels alongside pressure might improve survival and reduce brain pressure without additional heart or lung complications. However, some studies suggest this combined approach does not always result in better long-term brain health. Both methods are part of standard care, but the optimal approach remains unclear. ^{1 4 6 7 8}

Who Is on the Research Team?

Ramon Diaz-Arrastia, MD, PhD

Principal Investigator

University of Pennsylvania, Philadelphia, PA 19104

William Barsan, MD

Principal Investigator

University of Michigan, Ann Arbor, MI 48109

Sharon Yeatts, PhD

Principal Investigator

Medical University of South Carolina, Charleston, SC 29425

Lori Shutter, MD

Principal Investigator

University of Pittsburgh, Pittsburgh, PA 15260

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40122236/

Brain tissue oxygen combined with intracranial pressure ... Effective TBI management, aimed at minimizing secondary brain damage, requires constant monitoring of intracranial pressure (ICP) with or ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0967586822001163

Effects of brain tissue oxygen (PbtO2) guided management ... Our findings suggest that PbtO 2 -guided management: Increased survival and reduced intracranial pressure. Did not increase respiratory or cardiovascular ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9315682/

Brain Tissue Oxygenation-Guided Therapy and Outcome in ... The aim of this study was to assess the effectiveness of PbtO2-guided therapy in a single-center cohort. We performed a retrospective analysis ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1878875025002827

Brain Tissue Oxygen Combined with Intracranial Pressure ... The recent OXY-TC trial suggested that combined ICP + PbtO2 monitoring does not improve the 6-month neurological outcomes, prompting a meta-analysis.

5. aast.org aast.org/asset/FCE2120B-9962-46A6-AEBF429CC3DDD3CA/

Brain Oxygen Optimization in Severe Traumatic ... Objectives: A relationship between reduced brain tissue oxygen- ation and poor outcome following severe traumatic brain injury.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11468803/

Brain tissue oxygen pressure combined with intracranial ... The present study aimed to determine whether adding PbtO2 to intracranial pressure (ICP) monitoring improves clinical outcomes for patients with STBI.

7. thejns.org thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/30/2/article-p239.xml

Invasive brain tissue oxygen and intracranial pressure (ICP ... In Brief. There are limited data on brain tissue oxygen tension (PbtO2) monitoring and management in pediatric severe traumatic brain injury.

8. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(23)00290-9/abstract

Intracranial pressure monitoring with and without brain ... After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological ...