Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial

Hennepin Healthcare Research Institute, Minneapolis MN

Investigators

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Abstract

There continues to be an overarching problem of high mortality and poor neurologic outcomes for people who suffer severe traumatic brain injury (TBI). To date, no phase III trial has successfully demonstrated that any promising therapeutic agent improves clinically relevant outcomes in severe TBI. Preclinical investigations indicate that early administration of hyperbaric oxygen (HBO2) may improve TBI outcomes via several mechanistic pathways. By increasing oxygen (O2) delivery to the traumatized brain, HBO2 can reverse the ischemia that precipitates cellular energy failure and subsequent cellular death. HBO2 also reduces inflammation, decreases apoptosis, and promotes neurogenesis and angiogenesis. Early phase II clinical investigations have corroborated the preclinical work by demonstrating significant improvement in markers of oxidative metabolism, reduction in intracranial hypertension, and early signals of improvement in neurological outcome. However, prior to a definitive efficacy study, it is important to determine the optimal pressure for delivering HBO and whether normobaric hyperoxia (NBH) delivered following the HBO2 treatment enhances clinical efficacy. The Hyperbaric Oxygen in Brain Injury Treatment (HOBIT) trial was designed to de-risk a future phase III trial of Hyperbaric Oxygen Treatment (HBOT) in severe TBI by identifying the HBO2 treatment parameters that will enhance the chances of conducting a successful phase III trial. As of 7/22/2024, HOBIT has enrolled 127 out of a maximum of 200 participants. Due to multiple challenges, we did not achieve our target enrollment during the current award period. These challenges included the extensive preparations and HBO chamber modifications required for each site to safely enroll acutely injured severe TBI patients in a logistically complex trial, the suspension of non-COVID research at all enrolling sites during the pandemic, and challenges with hiring new research staff, respiratory technicians and ICU nurses following pandemic-related attrition. Currently, most enrollment sites have overcome their setbacks and are operational again. Participant enrollment from January to June 2024 was the highest for any six-month period since the trial began. A planned interim analysis conducted after the 116th enrollment revealed that the study has not yet reached any efficacy or futility criteria, necessitating further enrollment. In response to Funding Opportunity Number PAR-24-215, this renewal application requests additional time and funding to achieve the target sample size of 200 participants and to complete the trial successfully. The trial's primary aims are to optimize hyperoxia treatment parameters for severe TBI and to assess the likelihood of these treatments improving neurological outcomes at 6 months compared to standard care. Secondary objectives include analyzing intracranial pressure, brain tissue oxygen levels, and the rates of serious adverse events, as well as determining effective treatment paradigms.