Biomarkers in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Trial

Recruiting

• Conditions: TBI (Traumatic Brain Injury)
• Interventions: Other: No intervention. This is an observational study.

• Registration Number: NCT04565119
• Lead Sponsor: University of Pennsylvania

Brief Summary

BioBOOST is a multicenter, observational study of the effect of derangements in brain physiologic parameters on brain injury biomarker levels in patients with severe traumatic brain injury.

Detailed Description

This study is a prospective observational, multi-center study of subjects enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury-Phase 3 (BOOST-3) trial. BOOST-3 is a multicenter, randomized, blinded-endpoint, comparative effectiveness study of goal-directed critical care based upon monitoring of brain tissue oxygen and intracranial pressure versus monitoring of intracranial pressure alone in patients with severe traumatic brain injury.

The investigators will obtain an initial set of biospecimens (serum, plasma, cerebrospinal fluid (CSF), DNA and RNA) shortly after randomization into BOOST-3 and within 24 hours of injury. Subsequent biospecimens will be obtained every 8 hours for the first 24 hours post-enrollment. This will allow the characterization of acute changes in biomarker levels. On study days 2 through 5, biospecimens will be obtained twice a day to allow characterization of sub-acute changes in biomarker levels, without overburdening study teams or taking too much blood from individual subjects. On study days 7 and 14 and at 6-months post-enrollment, one set of biospecimen will be obtained, preferably in the morning. Biospecimens collected at each time point will consist of 6 ml of whole blood for serum extraction, 6 ml of whole blood for plasma extraction, 2.5 ml of whole blood for RNA extraction (a total of 14.5 ml \[one tablespoon\] of blood) and 5 ml of cerebrospinal fluid (CSF).

BioBOOST will utilize data collected in the BOOST-3 trial. This data includes: demographic data and clinical data such as injury characteristics, vital signs, head CT findings, laboratory data and data on physiologic parameters such as intracranial pressure (ICP), partial pressure of brain tissue oxygen (PbtO2), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP), among others.

BioBOOST will also utilize outcome assessment data collected from BOOST-3 participants at 6 months after injury (180 Days ± 30 days). Trained study personnel who are blinded to the treatment arm will administer the outcome assessments, which will include the measures listed below. The battery includes measures of functional status (GOSE), cognition, and emotional health. The 6-month follow-up interview will be done in person whenever possible. It may be done by telephone or video conference with participants where an in-person interview is not possible.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-07-01
• Study First Submitted QC: 2020-09-22
• Study First Posted: 2020-09-25
• Study Start: 2020-12-20
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-15
• Last Update Posted: 2024-04-16
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Enrolled in BOOST-3 (this is an ancillary study to the BOOST-3 trial)
• BOOST-3 participant is enrolled at a BioBOOST site
• Able to maintain initial blood sample within 24 hours of injury
• Provide proxy informed consent

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Exclusion Criteria

• Profoundly anemic (subjects who are profoundly anemic require blood transfusion)
• Age less than 18 years

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Severe traumatic brain injury (TBI)	No intervention. This is an observational study.	This observational study is ancillary to the Brain Oxygen Optimization in Severe TBI Phase 3 (BOOST-3) trial (NCT 03754114). All participants in Bio-BOOST are enrolled in BOOST-3.

Primary Outcome Measures

Name	Time	Method
Peak levels of glial fibrillary acidic protein (GFAP)	First 5 days after injury	This hypothesis will be tested via linear regression model, with peak GFAP level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 \< 20 mmHg during the first 48 hours of injury, quantified using area under the curve (AUC) methodology.
Peak levels of Tau	First 5 days after injury	This hypothesis will be tested via linear regression model, with peak Tau level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 \< 20 mmHg during the first 48 hours of injury, quantified using AUC methodology.
Peak levels of ubiquitin C-terminal hydrolase L1 (UCH-L1)	First 5 days after injury	This hypothesis will be tested via linear regression model, with peak UCH-L1level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 \< 20 mmHg during the first 48 hours of injury, quantified using AUC methodology.
Peak levels of neurofilament light chain (NfL)	First 5 days after injury	This hypothesis will be tested via linear regression model, with peak NfL level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 \< 20 mmHg during the first 48 hours of injury, quantified using AUC methodology.

Trial Locations

Locations (2)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Penn Presbyterian Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States