Cerebral edema is arguably the most serious complication of severe traumatic brain injury (TBI). The central HYPOTHESIS is that increasing osmolality of cerebrospinal fluid (CSF) will move free water out of tissue into the ventricles where it can be removed, thereby reducing cellular swelling, intracranial pressure (ICP), and cell death;ultimately improving cerebral function. Approach: The applicant proposes to undertake a pilot human study of an innovative catheter for the reduction of cerebral edema. The initial clinical application of this catheter will be severe TBI, and will involve replacing standard external ventricular drain (EVD) catheters with Reductive Ventricular Osmotherapy (RVOT) Catheters that 1) remove free water from CSF 2) remove bulk CSF acutely if needed to control ICP, and 3) monitor ICP. Removal of free water increases osmolality of the CSF, which will theoretically result in removal of interstitial brain water minimizing cerebral edema and improving nutrient exchange and Cerebral perfusion. A controlled study of experimental TBI in swine was performed, which demonstrated elevation of CSF osmolality, reduction in intracranial pressure (ICP), improvement in CSF chemistry variables such as lactate, and reduction in intracellular edema and cell death. Controls were treated with EVD catheters. The analyzed variables consistently indicated that RVOT produced either significant improvement or a favorable trend compared to EVD, supporting the central hypothesis that RVOT reduces cellular swelling and cell death while ultimately improving cerebral function.
Specific Aims : (I) The RVOT System design will be refined and tested to optimize performance for clinical studies and for obtaining FDA Investigational Device Exemption (IDE) approval. (II) A multicenter clinical study will be conducted to assess patient safety issues and effectiveness of RVOT in controlling ICP and intracellular edema in TBI patients.This pilot study of 15 patients at three sites is expected to demonstrate RVOT Catheter equivalence with conventional EVD catheters and provide clinical data to support the design of a pivotal study intended to demonstrate RVOT superiority to conventional drainage. ICP will be the primary endpoint. Study results will be used to support a FDA 510(k) product approval. Significance: Cerebral edema is a life threatening condition that is refractory to conventional treatments in a significant population of TBI and severe stroke patients. Completion of Phase II aims will make pivotal human studies of RVOT catheters possible.
In 2003 over 1.2 million Americans with traumatic brain injury were treated at hospitals emergency departments, 290,000 were hospitalized, and over 50,000 died. Secondary insults from cerebral edema may be responsible for one-third of TBI deaths. Innovative approaches to this problem have been lacking and the current therapies available to treat this critical medical condition are limited in their effectiveness.