SBIR-STTR Award

The technical challenges faced by pediatric cardiovascular physicians (surgeons and interventionalists alike) have long been ignored, forcing them to use devices designed for adults and different conditions to treat ailing babies with very specific anatomical considerations. One such case is in the sustained opening of the ductus arteriosus, a natural conduit that exists in all newborns but closes shortly after birth. In certain congenital heart defects, it is crucial to maintain ductus patency for the newborn to survive without surgical intervention. There is no ductus arteriosus stent commercially available in the US. Pediatric interventional cardiologists currently repurpose adult coronary artery stents for the ductus, and all-cause ductus reintervention is 47%. The alternative is surgery on a neonate to place a shunt that carries a 7.2% risk of morbidity and 13.1% risk of mortality in the US. Starlight Cardiovascular proposes creating and commercializing the first FDA-approved ductus arteriosus stent that is specifically designed to address the challenges facing treating physicians, including a right-sized delivery system, end-to-end coverage of the ductus, navigation and deployment through tortuous ductus anatomy, and precise placement to avoid stent protrusion into the aorta and pulmonary arteries. A stent designed and tested specifically for this purpose has the potential to decrease reinterventions, morbidity, and potentially mortality for babies with ductal-dependent circulation. This Phase I project involves developing test fixtures, stent prototyping and testing, and a preclinical animal study. Due to the variability of ductus anatomy, at least six benchtop anatomical models will be developed from 3D computational models of patient-specific anatomy. Starlight's stent and delivery systems will then undergo numerous iterations of designing, building and benchtop testing using the anatomical models to optimize the stent designs for deliverability, placement accuracy and radial force tailored to the challenging ductus anatomy. To select the final stent and delivery system design, the most promising stent designs will be implanted acutely in neonatal lambs to evaluate their performance in vivo. This Phase I project will result in the ultimate selection of the best ductus arteriosus stent and delivery system design to undergo design validation testing in Phase II in preparation for FDA approval.

Public Health Relevance Statement:
PROJECT NARRATIVE Babies born with congenital heart defects (CHDs) often need surgical interventions to survive. The devices available to treat them were designed and built for adult heart conditions and do not always perform as desired in babies. Starlight Cardiovascular plans to solve that problem by developing what will be the first FDA approved ductus arteriosus stent, which has the potential to save lives, reduce the number of procedures, and increase access to less invasive treatments for babies born with CHDs.

Project Terms:
Adult; 21+ years old; Adult Human; adulthood; Age; ages; Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; Animals; Aorta; Biomechanics; biomechanical; Birth; Parturition; Blood Circulation; Bloodstream; Circulation; Blood Vessels; vascular; Boston; Cardiovascular system; Cardiovascular; Cardiovascular Body System; Cardiovascular Organ System; Heart Vascular; circulatory system; Clinical Research; Clinical Study; Ductus Arteriosus; Equipment; Feedback; Fluoroscopy; Heart; Congenital Heart Defects; Congenital Cardiac Defects; congenital cardiac anomalies; Pediatric Hospitals; Children's Hospital; Newborn Infant; 0-4 weeks old; Newborns; newborn child; newborn children; Laboratories; Lasers; Laser Electromagnetic; Laser Radiation; Ligation; Closure by Ligation; Medical Device; Methods; Anatomic Models; Anatomical Models; Morbidity - disease rate; Morbidity; mortality; Patients; Physicians; Problem Solving; Production; Pulmonary artery structure; Pulmonary Artery; Risk; Spasm; Hyperkinesia; Hyperkinesis; Hyperkinetic Movements; Muscle Spasm; Muscular Spasm; Stents; Testing; Translating; Work; nitinol; Catheters; Device Designs; base; improved; Procedures; Coronary artery; Cardiac artery; Heart artery; Distal; Acute; Clinical; Phase; Ensure; Chemicals; Childhood; pediatric; Morphology; Shapes; tool; mechanical; Mechanics; Radius; Radial; In Situ; System; 3-D; 3D; three dimensional; 3-Dimensional; Shunt; shunts; Shunt Device; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; Surgeon; Performance; biomechanical engineering; Animal Models and Related Studies; model of animal; model organism; Animal Model; novel; Duct; Duct (organ) structure; Devices; Abscission; Extirpation; Removal; Surgical Removal; resection; Excision; Position; Positioning Attribute; Modeling; Property; Intervention Strategies; interventional strategy; Intervention; Address; Data; device development; instrument development; Device or Instrument Development; in vivo; Validation; Preparation; Development; developmental; pre-clinical; preclinical; neonate; design; designing; Outcome; Neonatal; Coupled; innovation; innovate; innovative; Implant; prototype; commercialization; FDA approved; Three Dimensional Medical Imaging; 3-D medical imaging; 3D medical imaging; mortality risk; death risk; Computer Models; Computerized Models; computational modeling; computational models; computer based models; computerized modeling

The technical challenges faced by pediatric cardiovascular physicians (surgeons and interventionalists alike) have long been ignored, forcing them to use devices designed for adults and different conditions to treat ailing babies with very specific anatomical considerations. One such case is in the sustained opening of the ductus arteriosus, a natural conduit that exists in all newborns but closes shortly after birth. In certain congenital heart defects, it is crucial to maintain ductus patency for the newborn to survive without surgical intervention. There is no ductus arteriosus stent commercially available in the US. Pediatric interventional cardiologists currently repurpose adult stents for the ductus, and all-cause ductus reintervention is 47%. The alternative is open-chest surgery on a neonate to place a shunt that carries a 13.1% risk of morbidity and 7.2% risk of mortality in the US. Starlight Cardiovascular proposes creating and commercializing the first FDA-approved ductus arteriosus stent that is specifically designed to address the challenges facing treating physicians, including a right-sized delivery system, end-to-end coverage of the ductus, navigation and deployment through tortuous ductus anatomy, and precise placement to avoid stent protrusion into the aorta and pulmonary arteries. A stent designed and tested specifically for this purpose has the potential to decrease reinterventions, morbidity, and potentially mortality for babies with ductal-dependent circulation. The feasibility of the innovative stent system designed for pediatric applications using self-expanding technology was demonstrated in a successful Phase I through numerous rounds of bench testing, physician evaluations, and an animal study; and this Phase II application proposes finalizing the stent design and completing preclinical testing necessary for a clinical trial and FDA approval. Through rapid iterations, Starlight will begin by optimizing the stent system for design characteristics and manufacturability. Starlight will then complete a chronic GLP animal study in 16 newborn lambs to demonstrate stent patency over 180 days. Verification and validation (V&V) testing of all aspects of the stent system (including biocompatibility, sterilization, and mechanical testing) will then be performed in accordance with FDA guidance documents for endovascular stents. This Phase II project will result in a finalized ductus arteriosus stent system design that has passed all of the necessary preclinical testing required for a clinical trial and subsequent FDA approval through the Humanitarian Device Exemption pathway.

Public Health Relevance Statement:
PROJECT NARRATIVE One percent of babies are born each year with Congenital Heart Disease (CHD), and these babies often require surgical intervention to survive. However, the devices that are currently used to treat this pediatric population were designed for adult cardiovascular conditions and do not always perform as intended in babies. Starlight Cardiovascular aims to solve this problem by developing a portfolio of devices for CHD, starting with what will be the first FDA-approved ductus arteriosus stent, which as the potential to save lives and increase access to less invasive treatments for babies born with CHD.

Project Terms:
Adult; 21+ years old; Adult Human; adulthood; Aging; Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; Animals; Aorta; Birth; Parturition; Blood Circulation; Bloodstream; Circulation; Cardiovascular system; Cardiovascular; Cardiovascular Body System; Cardiovascular Organ System; Heart Vascular; circulatory system; Clinical Trials; Disease; Disorder; Ductus Arteriosus; Face; faces; facial; Freezing; Congenital Heart Defects; Congenital Cardiac Defects; congenital cardiac anomalies; Newborn Infant; 0-4 weeks old; Newborns; newborn child; newborn children; Length of Stay; Number of Days in Hospital; hospital days; hospital length of stay; hospital stay; Medical Device; Anatomic Models; Anatomical Models; Morbidity - disease rate; Morbidity; mortality; Patients; Physicians; Problem Solving; Prostanoids; Prostaglandins; Pulmonary Artery; Pulmonary artery structure; Pulmonary Circulation; Risk; Safety; Stents; Technology; Testing; Device Designs; congenital heart disorder; congenital cardiac abnormality; congenital cardiac disease; congenital cardiac disorder; congenital cardiac malformation; congenital heart abnormality; congenital heart anomaly; congenital heart disease; congenital heart malformation; improved; Procedures; Coronary artery; Cardiac artery; Heart artery; Distal; Acute; Chronic; Clinical; Phase; Ensure; Evaluation; pediatric; Childhood; Life; mechanical; Mechanics; Investigation; Radius; Radial; In Situ; System; Thoracic Surgery; chest surgery; Thoracic Surgical Procedures; Shunt; shunts; Shunt Device; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; Surgeon; biocompatibility; biomaterial compatibility; success; novel; Duct; Duct (organ) structure; Devices; Modeling; Intervention Strategies; interventional strategy; Intervention; Address; Data; device development; instrument development; Device or Instrument Development; pre-clinical testing; Preclinical Testing; in vivo; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; Characteristics; Coronary; Shipping; Development; developmental; Pathway interactions; pathway; neonate; design; designing; Outcome; Population; Trauma; innovation; innovate; innovative; FDA approved; minimally invasive; good laboratory practice; verification and validation; flexibility; flexible; Sterilization; manufacturability; mortality risk; death risk; lamb model; design verification; design validation