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

项目摘要 意义：脑水肿在很大比例的严重创伤性脑损伤（TBI）病例中发生， 可能导致发病率恶化。渗透压梯度作为水肿原因的重要性已经被证实。 介绍了已发表的报告表明，脑水肿在许多患者中仍然是难治性的，目前所有 可用的治疗。转化研究已经确定渗透梯度的逆转作为一个要求 因此，迫切需要新的脑水肿疗法来管理 渗透压和流体静压梯度。 创新：减少心室渗透压治疗（RVOT）通过去除 来自脑室中的脑脊液（CSF）的游离水。通过渗透蒸发除去CSF水 通过嵌入式中空纤维膜，干燥空气吹扫气去除水蒸气。增加 然后心室渗透压导致水从组织中流出并进入心室 通过RVOT导管通过持续渗透蒸发或流体静力学整体引流机制清除。 假设：我们的假设是，脑室注射治疗将通过流体静力学和渗透性减少脑水肿。 机制，从而提供安全和有效的援助，以改善TBI管理。 初步数据：该假设基于已发表的大型动物实验的初步数据。 TBI研究表明RVOT可显著增加CSF渗透压。RVOT治疗导致 改善表观弥散系数和其他脑水肿减轻的证据。 预期影响：RVOT将为临床医生提供一种结合当前和未来干预措施的新工具 改善TBI患者的预后。 SBIR第一阶段：获得临床前试验数据的临床研究批准。 SBIR II期：评估RVOT作为ICP管理辅助器械的临床安全性和有效性。第一阶段- 人体安全性研究：入组10例插入和管理RVOT导管的重度TBI患者， 将安全性作为主要终点。2a期随机对照初步试验：入组40例重度TBI 患者以3：1的比例随机接受RVOT（n=30）或标准治疗脑室体外引流（n=10）治疗， 评估RVOT安全性、有效性和经济可行性终点，总体目标是实现 SBIR III期关键研究，以获得上市许可和RVOT系统产品商业上市。 商业化计划：SBIR快速通道项目提供了一个高度可信的商业化途径 基于大型动物可行性研究支持的重大未满足的医疗需求，公司合作伙伴 前景，和经验丰富的神经创伤设备，临床和商业团队。

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.