Pilot Clinical Study to Assess Safety and Efficacy of External Ventricular Drainage with Cerebrospinal Fluid Water Removal Osmotherapy for Traumatic Brain Injury-Induced Cerebral Edema

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Project Summary Significance: Cerebral edema develops in a large percentage of severe traumatic brain injury (TBI) cases and may lead to worsened morbidity. The importance of osmotic gradients as the cause of edema has been described. Published reports indicate cerebral edema remains refractory in many patients to all currently available treatments. Translational research has identified reversal of the osmotic gradient as a requirement for treating cerebral edema; therefore, there is a critical need for new cerebral edema therapies to manage both osmotic and hydrostatic pressure gradients. Innovation: Reductive Ventricular OsmoTherapy (RVOT) manages osmotic pressure gradients by removing free water from the cerebrospinal fluid (CSF) in the brain ventricles. CSF water is removed by pervaporation through embedded hollow fiber membranes, as a dry air sweep gas removes water vapor. Increased ventricular osmotic pressure then causes water movement out of the tissue and into the ventricles where it is removed by the RVOT catheter by either continued pervaporation or a hydrostatic bulk drainage mechanism. Hypothesis: Our hypothesis is ventricular osmotherapy will reduce cerebral edema by hydrostatic and osmotic mechanisms, and thereby provide a safe and efficacious aid to improve TBI management. Preliminary Data: This hypothesis is based on published preliminary data with a large animal experimental TBI study demonstrating that RVOT can significantly increase CSF osmolality. RVOT treatment resulted in improved Apparent Diffusion Coefficient and other evidence of reduced cerebral edema. Expected Impact: RVOT will provide clinicians a new tool in combination with current and future interventions to improve TBI patient outcomes. SBIR Phase I: Obtain clinical study approval with pre-clinical test data. SBIR Phase II: Assess RVOT clinical safety and efficacy as an ICP management aid device. Phase 1 First- In-Human Safety Study: Enroll 10 severe TBI patients with insertion and management of RVOT catheter to assess safety as primary endpoint. Phase 2a Randomized Controlled Pilot Trial: Enroll 40 severe TBI patients randomized 3:1 to RVOT (n=30) or standard-of-care external ventricular drain (n=10) therapy to assess RVOT safety, efficacy and economic feasibility endpoints, with the overall objective of enabling an SBIR Phase III pivotal study to obtain market authorization and RVOT System product commercial launch. Commercialization Plan: This SBIR Fast Track project offers a highly credible commercialization pathway based on a significant unmet medical need supported with a large animal feasibility study, corporate partner prospects, and experienced neurotrauma device, clinical, and commercial team.