Aneurysmal subarachnoid hemorrhage (SAH) is a devastating neurological condition occurring as the result of a ruptured cerebral aneurysm. The mean incidence is 11 people per 100,000 population and an estimated 30,000 cases annually in the US. After securement of a ruptured aneurysm, patients are closely observed in the hospital for 14 days to monitor for cerebral vasospasm, edema, hydrocephalus and for the body to slowly clear any remaining blood from the subarachnoid space. Due to the prevalence of these complications, there remains a significant unmet need to improve outcomes for these patients. Early removal of blood and blood products (e.g. hemoglobin, oxyhemoglobin, and downstream inflammatory proteins) from the cerebrospinal fluid (CSF) has been shown to reduce the incidence of vasospasm, stroke, hydrocephalus, the need for permanent shunt placement, and result in a shorter hospital course. Currently available tools, such as passive ventricular or lumbar drains, however, are not sufficient for expedited blood removal. Our central hypothesis is that blood and blood breakdown products from the CSF can be directly targeted and rapidly reduced, using a novel, interventional approach. Minnetronix, a medical device development and manufacturing company, has developed an automated CSF treatment and filtration platform. The closed-loop device extracts contaminated CSF from the lumbar cistern and reintroduces cleaned CSF back into the cervico-thoracic subarachnoid space (a process termed Neurapheresis), processing CSF at up to 2 ml/min. Neurapheresis therapy is an innovative, new therapeutic option that is intended to be complementary, and does not replace standard of care interventions, for patients with SAH. The first-in-human trial (PILLAR study- 15 patient study, preliminary data in this application) was reviewed by the DSMB and had unanimous support for safety and an expanded clinical study. The pilot study demonstrated a mean of 632.0 mL of CSF processed in 15:07 hours of filtration and initially elevated mean CSF total protein and RBCs were reduced by 71.0% and 57.9%, respectively. The PILLAR Extension protocol (termed PILLAR XT), proposed in this grant, was reviewed and approved by FDA and the central IRB. This study will directly measure performance of a CSF flow algorithm alongside continued evaluation of the device safety, with the addition of automation and longer therapy time. The study will further explore continued reduction of blood in the cranial and spinal subarachnoid space with Neurapheresis therapy. In PILLAR XT, the larger sample size (30 patients) and longer duration (up to 36 hours of pump time in Phase I and limited only by catheter indwelling time of 72 hours in Phase II) will allow more efficacy data to power a future pivotal study. This data will contribute to system optimization, refinement of the protocol and selection of the appropriate endpoints for a future pivotal study. The long-term goal is to develop an automated, cost- effective platform with bedside catheter placement that rapidly removes blood from CSF and translates to reduced morbidity and mortality for aneurysmal SAH.
Public Health Relevance Statement: NARRATIVE In the US, there are ~30,000 cases of aneurysmal subarachnoid hemorrhage (SAH) annually. SAH patients can develop complications post-aneurysm securement, ranging from vasospasm and stroke to shunt- dependent hydrocephalus, the lasting effects of these episodes can be devastating. Minnetronix has developed an innovative therapeutic platform designed to rapidly filter and reduce blood and blood breakdown products from the cerebrospinal fluid (CSF), a process termed Neurapheresis. A first-in-human 15 patient clinical trial (PILLAR) was recently completed and found Neurapheresis to safely reduce blood in the cranial and spinal subarachnoid space. In an expanded FDA-approved clinical study (PILLAR XT), Minnetronix plans to further evaluate an automated Neurapheresis platform with increased therapy time to guide system improvements and design of an upcoming pivotal clinical study.
NIH Spending Category: Assistive Technology; Bioengineering; Brain Disorders; Cerebrovascular; Clinical Research; Clinical Trials and Supportive Activities; Hydrocephalus; Neurosciences; Orphan Drug; Patient Safety; Rare Diseases; Stroke
Project Terms: Achievement; Adverse event; Affect; Algorithms; Aneurysm; Aneurysmal Subarachnoid Hemorrhages; Automation; Back; Blood; blood product; Catheters; Cells; Cephalic; Cerebral Aneurysm; Cerebral Ischemia; Cerebrospinal Fluid; cerebrospinal fluid flow; Cerebrovascular Spasm; Clinical; Clinical Engineering; Clinical Research; Clinical Trials; cost effective; Data; Data Collection; design; Device or Instrument Development; Device Safety; Devices; Drainage procedure; Edema; efficacy study; Endpoint Determination; Enrollment; Erythrocytes; Evaluation; Excision; FDA approved; Filtration; first-in-human; Focal Neurologic Deficits; functional outcomes; Future; Goals; Grant; Hemoglobin; Hemorrhage; Hospital Mortality; Hospitals; Hour; Hydrocephalus; Image; improved; improved outcome; Incidence; Indwelling Catheter; Infection; Inflammation; Inflammatory; innovation; Institutional Review Boards; Intervention; Lead; Length of Stay; Liquid substance; Manuals; Measures; Medical Device; Methods; Monitor; Morbidity - disease rate; mortality; neuroinflammation; Neurologic; novel; novel therapeutics; operation; Oxyhemoglobin; patient safety; Patient-Focused Outcomes; Patients; Performance; Phase; Pilot Projects; Population; pressure; Prevalence; Process; Proteins; Protocols documentation; Pump; Red Blood Cell Count; Rupture; Ruptured Aneurysm; Safety; Sample Size; Sampling; Secure; Shunt Device; Spinal; standard of care; Stroke; Subarachnoid Hemorrhage; Subarachnoid Space; Sum; System; Testing; Therapeutic; Time; tool; Translating; treatment duration; trend; Vasospasm; Ventricular; X-Ray Computed Tomography
