SBIR-STTR Award

Direct to Phase II

Stroke, including ischemic stroke, is the 2nd leading cause of death in the world and 5th leading cause of deathin the United States. Recent breakthrough advances in device technology have resulted in endovascular stroketreatment becoming the standard of care. However, stroke thrombectomy (intervention) is time sensitive with awindow to intervene in less than 16 hours following symptom onset. Patients rarely arrive to the care facilityimmediately following the onset of symptoms. It is well-known that complications directly increase in proportionto procedure time, specifically 1) a 7.7% decreased probability of functional independence for every hour ofstroke onset to successful reperfusion ("time is brain" concept), and 2) sometimes death. In addition, these timesensitive procedures are limited due to tortuous anatomy, prevalent in the elderly (in up to 35%). This in turnalso results in higher complication rates and lessens the chance of procedural success. Specifically,neurointerventionalists struggle with difficult anatomy and often are unable to perform these potentially life-savingprocedures in 28.9% of patients. Not only is there a delay in reaching the target intracranial artery, but radiationexposure and contrast dose can also rise, placing the patient at additional risk. Therefore, there is a tremendousneed for a device to decrease the failure rate and improve the speed of this procedure in difficult tortuous aorticanatomy. RAM Medical Innovations (RAM) has developed a novel carotid sheath that can quickly and safelynavigate as well as maintain stable position in this hostile anatomy. RAM's feasibility work showed significantlyfaster carotid sheath insertion success rate, less endothelial injury, and reduced radiation exposure with ournonlubricious prototype against predicate devices, all of which have an advantageous hydrophilic coating. In thisDirect to Phase 2 grant RAM plans to make and test the finalized, lubricious sheath device to demonstrate theproduct's safety and time efficiency profile. Notably, RAM's device, using a lubricious component found in otherFDA approved devices seeks to reduce the potential risk of particle shedding seen with current predicates. Inpreparation for FDA 510(k) application, Class II device, RAM proposes biocompatibility testing in compliancewith the FDA guidelines and ISO protocols. This would include cytotoxicity, sensitization, irritation, systemictoxicity (acute) and hemocompatibility, using in vitro and animal models to establish measurements withinacceptable ranges. RAM also plans to perform device sterilization, design verification, packaging andaccelerated aging tests that will ensure that the product will perform reliably one-year and two-years poststerilization. Packaging and sterilization testing will also be completed to conform to FDA and ISO standards.Additionally, after each testing process, the device will be functionally tested to ensure that the design is stillrobust. Successful outcomes in testing and development will result in a new promising tool to deliver stroketreatment efficiently and safely even in patients with difficult aortic anatomy. RAM has obtained third partyinvestments and, after obtaining FDA clearance, intends to partner with or sell the product to a major medicaldevice manufacturer for commercial deployment.

Public Health Relevance Statement:
Project Narrative There is a critical unmet need for devices to efficiently deliver a carotid sheath to the carotid and/or intracranial circulation in difficult anatomy during stroke intervention. RAM Medical designed a proprietary sheath device that can safely, reliably and quickly access the intervention site with a stent or thrombectomy device in minutes versus hours and makes impossible cases, possible to treat. As time is of essence in treating stroke, RAM believes the device has the potential to significantly advance the field of stroke intervention and reduce the incidence of serious disability or death.

Project Terms:
Adhesions ; Elderly ; advanced age ; elders ; geriatric ; late life ; later life ; older adult ; older person ; senior citizen ; Aging ; Anatomy ; Anatomic ; Anatomic Sites ; Anatomic structures ; Anatomical Sciences ; aortic arch ; aorta arch ; Autopsy ; necropsy ; postmortem ; Blood ; Blood Reticuloendothelial System ; Blood Circulation ; Bloodstream ; Circulation ; Blood Platelets ; Marrow platelet ; Platelets ; Thrombocytes ; Blood Vessels ; vascular ; Brain ; Brain Nervous System ; Encephalon ; Cadaver ; Carotid Arteries ; Cause of Death ; Classification ; Systematics ; Complication ; Data Analyses ; Data Analysis ; data interpretation ; Cessation of life ; Death ; Therapeutic Embolization ; Embolization Therapy ; Embolotherapy ; embolization ; Endothelium ; Vascular Endothelium ; Feasibility Studies ; Fluoroscopy ; Grant ; Cyclic GMP ; Guanosine Cyclic Monophosphate ; cGMP ; Health care facility ; Health Facilities ; Healthcare Facility ; care facilities ; Human ; Modern Man ; Humidity ; In Vitro ; Incidence ; Investments ; Medical Device ; Legal patent ; Patents ; Patients ; Probability ; Reperfusion Therapy ; reperfusion ; Risk ; Safety ; Savings ; seal ; Sheep ; Ovine ; Ovis ; Silicones ; Stents ; Stroke ; Apoplexy ; Brain Vascular Accident ; Cerebral Stroke ; Cerebrovascular Apoplexy ; Cerebrovascular Stroke ; brain attack ; cerebral vascular accident ; cerebrovascular accident ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; Technology ; Temperature ; Testing ; Time ; United States ; Work ; Measures ; Catheters ; Thrombectomy ; Guidelines ; Injury ; injuries ; Tube ; base ; improved ; Procedures ; Site ; Acute ; Clinical ; Phase ; Medical ; Ensure ; Evaluation ; Endothelial Cells ; disability ; Failure ; Cerebrum ; cerebral ; Measurement ; radiologist ; tool ; Life ; Hour ; irritation ; Protocol ; Protocols documentation ; intracranial artery ; Test Result ; Particulate ; biocompatibility ; biomaterial compatibility ; Lytotoxicity ; cytotoxicity ; 65+ years old ; Aged 65 and Over ; age 65 and greater ; age 65 and older ; aged 65 and greater ; aged ≥65 ; old age ; human old age (65+) ; particle ; Performance ; success ; hydrophilicity ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Speed ; novel ; Devices ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Position ; Positioning Attribute ; Modeling ; stroke treatment ; treating stroke ; stroke therapy ; Intervention Strategies ; interventional strategy ; Intervention ; Manufacturer ; Manufacturer Name ; Ischemic Stroke ; preventing ; prevent ; Clotting ; Coagulation ; Coagulation Process ; Dose ; Symptoms ; Data ; in vivo ; Preparation ; Process ; Shipping ; Development ; developmental ; design ; designing ; next generation ; Outcome ; innovation ; innovate ; innovative ; Resistance ; resistant ; prototype ; FDA approved ; standard of care ; Sterilization ; phase 2 study ; phase II study ; head-to-head comparison ; head-to-head analysis ; neurovascular ; neuro-vascular ; systemic toxicity ; stroke intervention ; Radiation exposure ; functional independence ; hemocompatibility ;