SBIR-STTR Award

Non-traumatic IntraCerebral Hemorrhage (ICH) is caused by a rupture of vessels which bleed directly into the brain tissue, forming a gradually enlarging hematoma (pooling of blood). In 40% of ICH cases, the ICH is associated with bleeding into the ventricles causing IntraVentricular Hemorrhage (IVH). In ICH and IVH, faster resolution of hematoma can significantly influence patient's chances of survival with minimum brain damage and reduced burden of neurologic deficits. EKOS MicroSonicTM SV device is an ultrasound based micro catheter that has demonstrated the safety and efficacy of the concept of ultrasound-assisted thrombolysis in treatment of ICH/IVH in a clinical study, Safety of Lysis with EKOS Ultrasound in the Treatment of Intracerebral and Intraventricular Hemorrhage (SLEUTH). SLEUTH employed a combination of EKOS ultrasound micro catheter, designed for treatment of ischemic stroke and an external ventricular drainage catheter. This combination was perceived quite challenging for use by clinicians. We seek to transfer this concept to a reliable product that can easily be utilized by clinicians in a wider clinical trial. We intend to design and develop a single device for ultrasound assisted thrombolytic delivery and drainage of the liquefied clot in ICH and IVH. This single device will be under consideration to participate in on-going clinical trials in ICH (MISTIE III) and IVH (CLEAR III). EKOS Corporation, a privately held company based in Bothell, Washington, is the world leader in providing ultrasound-accelerated drug delivery devices for diagnosis and therapy. The company's Peripheral Infusion System received FDA clearance through a 510(k) notification in 2004 and CE mark approval in 2005. EKOS Microcatheter was cleared by FDA in the United States for use in peripheral vessels in 2003 and regional infusion of contrast material in neurovasculature in 2005. Upon demonstration of promising results in a NIH sponsored phase II study of Interventional management of ischemic stroke (IMS II), this device is currently participating in IMS III clinical trial. However; the microcatheter received approval for CE mark in 2005 and is commercially available in Europe at present time. EKOS Infrastructure includes on-site Research and Development, Manufacturing, Marketing, Sales, Finance, Quality Assurance, Regulatory and Clinical Affairs. This infrastructure and experience in microsonic technology gives EKOS team a unique advantage to carry out the following milestones leading towards a product ready for clinical use: Milestone 1: Define software and hardware specifications for the proposed product; Milestone 2: Construct a prototype device and develop associated software; Milestone 3: Test feasibility of the prototype device; Milestone 4: Review, verify and validate the product design specifications; Milestone 5: Document final system design; Milestone 6: Submit an application to obtain FDA approval for the clinical use of the new product; Milestone 7: Build devices to support clinical trial.

Public Health Relevance:
Non-traumatic spontaneous IntraCerebral Hemorrhage occurs due to bleeding of a ruptured artery in the brain. 40% of ICH cases are associated with bleeding into the ventricles of the brain or IntraVentricular Hemorrhage (IVH). 30-day mortality rate for ICH is 30-40% with half the number of deaths taking place in the first 48 hours after onset. The incidence of IVH has mortality estimates between 50 to 80%. Clotting is initiated by local activation of hemostatic pathways and mechanical tamponade. Faster evacuation of clot with lytic therapy leads to speedy resolution of the hemorrhage improving patient's chances of survival with minimum brain damage and reduced burden of neurologic deficits. The SLEUTH study (Safety of Lysis with EKOS Ultrasound in the Treatment of Intracerebral and Intraventricular Hemorrhage (SLEUTH)) was designed to assess the safety of enhancing the lysis rate of hemorrhagic clot by delivering a combination of ultrasound and low-dose rt-PA (Activase(r), Genentech, CA) into the clots in ICH and IVH. Ultrasound and drug were delivered by placement of the MicroSonicTM SV catheter (EKOS Corporation, Bothell, WA) adjacent to an external ventricular drain catheter positioned in the hemorrhagic clot. The preliminary data evaluation of this study suggests exceptional improvement in the speed of clot removal without any increase in adverse events. The proposed product development project will deliver a single device which is designed for ultrasound-assisted thrombolysis and evacuation of the liquefied clot. This project will develop an ultrasonic drain catheter for rapid removal of clotted hematoma. The project holds the potential of reducing healthcare costs in treatment of intracranial hemorrhage and bringing benefits to patients & clinicians.

Public Health Relevance Statement:
Project Narrative Non-traumatic spontaneous IntraCerebral Hemorrhage occurs due to bleeding of a ruptured artery in the brain. 40% of ICH cases are associated with bleeding into the ventricles of the brain or IntraVentricular Hemorrhage (IVH). 30-day mortality rate for ICH is 30-40% with half the number of deaths taking place in the first 48 hours after onset. The incidence of IVH has mortality estimates between 50 to 80%. Clotting is initiated by local activation of hemostatic pathways and mechanical tamponade. Faster evacuation of clot with lytic therapy leads to speedy resolution of the hemorrhage improving patient's chances of survival with minimum brain damage and reduced burden of neurologic deficits. The SLEUTH study (Safety of Lysis with EKOS Ultrasound in the Treatment of Intracerebral and Intraventricular Hemorrhage (SLEUTH)) was designed to assess the safety of enhancing the lysis rate of hemorrhagic clot by delivering a combination of ultrasound and low-dose rt-PA (Activase(R), Genentech, CA) into the clots in ICH and IVH. Ultrasound and drug were delivered by placement of the MicroSonicTM SV catheter (EKOS Corporation, Bothell, WA) adjacent to an external ventricular drain catheter positioned in the hemorrhagic clot. The preliminary data evaluation of this study suggests exceptional improvement in the speed of clot removal without any increase in adverse events. The proposed product development project will deliver a single device which is designed for ultrasound-assisted thrombolysis and evacuation of the liquefied clot. This project will develop an ultrasonic drain catheter for rapid removal of clotted hematoma. The project holds the potential of reducing healthcare costs in treatment of intracranial hemorrhage and bringing benefits to patients & clinicians.

Project Terms:
Abscission; Acoustic; Acoustics; Acquired brain injury; Activase; Adverse event; Adverse Experience; Affect; After Care; After-Treatment; Aftercare; American; Apoplexy; Apoptosis; Apoptosis Pathway; Arteries; base; Biologic Sciences; Biological Sciences; Bleeding; Blood; Blood - brain barrier anatomy; blood loss; Blood-Brain Barrier; Brain; brain attack; brain cell; brain damage; Brain Hemorrhage, Cerebral; Brain Hemorrhage, Cerebral, Traumatic; Brain Injuries; brain lesion (from injury); brain tissue; Brain Ventricle; Catheters; Cell Death, Programmed; Cephalic; Cerebral hemisphere hemorrhage; Cerebral Hemorrhage; Cerebral Parenchymal Hemorrhage; Cerebral perfusion pressure; Cerebral Stroke; cerebral vascular accident; Cerebral Ventricles; Cerebrovascular accident; Cerebrovascular Apoplexy; Cerebrovascular Stroke; Cessation of life; Clinical; clinical investigation; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Unspecified; Clotting; Coagulation; Coagulation Process; Collaborations; computer program/software; Computer Programs; Computer software; Cranial; Cytolysis; Data; Death; design; designing; Development; Development and Research; Devices; Diagnosis; Diagnosis, Ultrasound; diagnostic ultrasound; Dose; Drainage; Drainage procedure; Drug Delivery; Drug Delivery Systems; Drug Targeting; Drug Targetings; drug/agent; Drugs; Echography; Echotomography; Encephalon; Encephalons; Europe; Evaluation; Evaluation Studies; Excision; experience; Extirpation; fibrinogenase; Forecast of outcome; Frequencies (time pattern); Frequency; Funding; Genentech Brand of Alteplase; gitter cell; Goals; Health Care Costs; Health Costs; Healthcare Costs; heavy metal lead; heavy metal Pb; Hemato-Encephalic Barrier; Hematoma; Hemoglobin; Hemorrhage; Hemorrhage, Cerebrum; Hemostatic Agents; Hemostatics; Hoffmann-La Roche Brand of Alteplase; Hortega cell; Hour; improved; Incidence; Independent Living; Infrastructure; Infusion; Infusion procedures; Injury; Institutes; intervention design; Intracerebral Hemorrhage; Intracerebral Hemorrhage, Traumatic; Intracranial Hemorrhages; intraventricular hemorrhage; Ischemic Stroke; Lead; Life Sciences; local drug delivery; Lysis; Lytic; Marketing; Mechanics; Medical; Medical Imaging, Ultrasound; Medication; mesoglia; Microglia; microglial cell; microgliocyte; minimally invasive; Minor; Modification; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; National Institutes of Health; National Institutes of Health (U.S.); Nervous System, Brain; Neurologic Deficit; NIH; Notification; Operation; Operative Procedures; Operative Surgical Procedures; Outcome; outcome forecast; pathway; Pathway interactions; Patients; Pb element; Peripheral; perivascular glial cell; Pharmaceutic Preparations; Pharmaceutical Preparations; phase 2 study; Position; Positioning Attribute; Process; product development; Prognosis; Protocol; Protocols documentation; prototype; public health relevance; quality assurance; R & D; R&D; Removal; Reporting; research and development; Research Infrastructure; resection; Resolution; Reticuloendothelial System, Blood; Rupture; Safety; safety study; Sales; Site; Software; sonogram; sonography; sound measurement; Speed; Speed (motion); Stroke; stroke; surgery; Surgical; Surgical Interventions; Surgical Procedure; Surgical Removal; Survivors; System; System, LOINC Axis 4; Technology; Testing; therapy design; Thrombase; Thrombin; thrombolysis; Time; Traumatic cerebral hemorrhage; Traumatic Cerebral Intraparenchymal Hemorrhage; Traumatic Cerebral Parenchymal Hemorrhage; treatment design; Ultrasonic; Ultrasonic Imaging; Ultrasonics; Ultrasonogram; Ultrasonography; ultrasound; ultrasound imaging; ultrasound scanning; Ultrasound Test; Ultrasound, Medical; United States; United States National Institutes of Health; Universities; Vascular Accident, Brain; Ventricular; Washington