Biomarkers in the Brain Oxygen Optimization in Severe TBI Trial (Bio-BOOST)

Traumatic brain injury (TBI) remains a major cause of death and disability, with an estimated cost of $45 billion/year in the United States alone. Of the 300,000 hospital admissions for TBI annually, approximately 40% are classified as severe TBI, and there are currently limited objective tools for personalization of TBI treatment and for monitoring response to novel therapies. Blood and cerebrospinal fluid (CSF) levels of structural proteins components of brain cells that are released in the aftermath of brain injury may be a promising adjunct for detecting and monitoring secondary brain injury. The recently launched BOOST-3 (Brain Oxygen Optimization in Severe TBI Phase 3) trial offers a unique opportunity to study and validate biomarkers and therefore accelerate our understanding of the pathophysiology of severe TBI, and promote the development of effective interventions. BOOST-3 will enroll 1094 participants with severe TBI from 2018 2023 representing a federal investment. Capitalizing on the infrastructure of BOOST-3, we propose conducting an ancillary biomarker study, Bio-BOOST. Our primary objective is to quantify the effect of total brain tissue hypoxia exposure on brain injury using biofluid-based biomarkers of brain injury. We hypothesize that total brain tissue hypoxia exposure within 48 hours of randomization is independently associated with higher peak levels of biomarkers of astrocytic (GFAP) and axonal (UCH-L1, Total Tau and NFL) injury, after adjusting for age, gender, and time between injury and randomization.