Thrombolex, Inc. has developed an intravascular catheter with an expandable spiral basket of infusion limbs to improve the efficacy of catheter-directed thrombolysis (CDT) in large vessels. Preclinical studies indicate administration of recombinant tissue plasminogen activator (rtPA) via the Bashir Endovascular Catheter (BEC) reduces thrombus burden to a greater degree than non-expandable CDT devices. Successful commercialization of the BEC has the potential to reduce the dose of thrombolytic agents administered to patients with large vessel thrombosis, shorten the duration of infusion, and substantially improve short- and long-term outcomes compared to current CDT devices. Up to 900,000 Americans are affected by pulmonary embolism (PE) or deep vein thrombosis each year.1 Large thrombi can produce a sudden obstruction of the pulmonary arteries (PA), failure of the right ventricle (RV), and cardiovascular collapse. While CDT reduces RV/LV ratio and improves RV function,3 the current small diameter catheters deliver thrombolytics to only a small cross-section of a thrombus and reduce its size by ? 30%. We expect the BEC will outperform current CDT devices and improve patient outcomes by three mechanisms: 1) expansion of the basket creates a large channel within the thrombus, restoring blood flow; 2) thrombolysis is markedly accelerated by this large channel, increasing the surface area exposed to both the infused thrombolytic and endogenous fibrinolytics, which has a synergistic effect;4 and 3) the device allows the medical team to measure PA pressure and mixed venous O2 sat to monitor thrombolysis and ideally reduce the duration/dose of thrombolysis, thereby reducing bleeding complications without sacrificing efficacy. In preclinical porcine studies, we demonstrated that 1) expanding the BEC restores blood flow, 2) infusion of rtPA via the expanded basket reduced thrombus volume by >80% after only 4 hours, and 3) the BEC did not cause endothelial damage. FDA cleared the BEC for use in the peripheral vasculature but determined further testing is needed prior to clearance for use in PE since the expandable basket is an innovation that could affect safety or effectiveness. A 10-patient Early Feasibility Study (EFS) is underway, and here we propose a Direct-to-Phase II SBIR project to support a ten-site, two-year pivotal trial with 125 patients as an essential step in toward commercialization. Aim. To evaluate the effectiveness of BEC-delivered rtPA in improving RV size and function in patients with acute submassive PE. Success Criteria: Full enrollment; acquisition and analysis of data on primary/secondary endpoints; demonstration of efficacy: ³ 20% reduction in RV/LV ratio; 510(k) submission. Team Includes Dr. Riyaz Bashir, Dr. Brian Firth, and Mr. Marvin Woodall; Advisory Board and trial Steering Committee include Drs. Anthony Comerota, Kenneth Rosenfield, and Akhilesh Sista. Impact This project will provide efficacy data to satisfy FDA requirements and support a 510(k) application with an indication for submassive PE. Clinical availability of the BEC has the potential to improve survival, reduce complications from bleeding, and reduce long-term effects of acute PE.
Public Health Relevance Statement: PROJECT NARRATIVE Up to 900,000 Americans are affected by pulmonary embolism (PE) or deep vein thrombosis each year, and up to 12% of patients with submassive PE die within 90 days, despite the availability of multiple advanced therapies including catheter-directed therapy in which a long tube is inserted into the blood clot to improve the delivery of clot-dissolving drugs. The proposed Direct-to-Phase II SBIR project is designed to test whether adding an expandable spiral basket of drug delivery tubes to the end of the catheter helps dissolve the clot faster and to a greater extent than existing devices. If successful, this project will provide data that the FDA needs to approve this device for clinical use, which has the potential to improve patient survival, reduce complications from bleeding, and reduce the long-term effects associated with submassive PE.
Project Terms: Acute; Address; Adverse effects; Affect; Alteplase; American; Area; Blood; Blood coagulation; Blood flow; Caliber; cardiovascular collapse; Catheters; Clinical; Coagulation Process; commercialization; compare effectiveness; Data; Data Analyses; Deep Vein Thrombosis; design; Devices; Dose; Drug Delivery Systems; Effectiveness; effectiveness evaluation; efficacy trial; eligible participant; Endothelium; Enrollment; exercise capacity; Exposure to; Failure; Family suidae; Feasibility Studies; Fibrinolytic Agents; Hemorrhage; Hour; improved; Infusion procedures; innovation; Life; Limb structure; Long-Term Effects; Measures; Medical; Monitor; mortality; multi-site trial; novel; Obstruction; Outcome; Oxygen; Patient-Focused Outcomes; Patients; Peripheral; Pharmaceutical Preparations; Phase; pre-clinical; preclinical study; pressure; primary endpoint; Pulmonary artery structure; Pulmonary Embolism; Reporting; restoration; Right ventricular structure; Risk; Safety; Savings; secondary endpoint; Site; Small Business Innovation Research Grant; success; Surface; Symptoms; Testing; thrombolysis; Thrombosis; Thrombus; Tube; Venous
