Presentation

Background and Purpose: A relationship between reduced brain tissue oxygenation (PbtO2) and poor outcome following severe traumatic brain injury (sTBI) has been reported in several trials, including a Phase II randomized trial.

Methods: Large single-blind, randomized, controlled, phase 3, multi-center parallel studies examining brain oxygenation optimization are occurring internationally (BOOST-3: North America; BONANZA: Australia, New Zealand, and Europe). These trials will assess for benefit of multimodal ICP plus PbtO2 directed management on functional outcome in sTBI. The target population for both studies are patients presenting with acute sTBI requiring intracranial pressure monitoring and randomized within 12 hours from injury, using an exception from informed consent where allowable. Patients are randomized to receive tiered management interventions aimed at treating either ICP and PbtO2 or ICP only. Primary outcome measure in both studies is a blinded 6-month post-injury GOS-E, with BOOST-3 utilizing a sliding dichotomy analysis approach based on the IMPACT Core Model and BONANZA using a fixed dichotomy where GOS-E>4 is a favorable outcome.

Results: Target enrollment is statistically powered within each study with current enrollment of BOOST-3: 608/1094 at 44 sites and BONANZA: 121/860 at 15 sites. Demographics in each study are comparable with average age 40 years, 39 years; 81%, 79% male and mean initial GCS score 6 and 5, BOOST-3 and BONANZA, respectively.

Conclusion: Unique in the planning processes of trial design was foresight to allow for a future IPDMA (individual patient data meta-analysis), which requires the harmonization of many data elements across studies. Thus far, this is a targeted achievement.