DUCTUS ARTERIOSUS STENT TO IMPROVE CONGENITAL HEART DEFECT MORTALITY

摘要 儿科心血管医生（外科医生和介入医生）面临的技术挑战 长期以来一直被忽视，迫使他们使用为成人设计的设备和不同的条件来治疗生病 有特殊解剖学考虑的婴儿一个这样的例子是在持续开放的导管 动脉，一种存在于所有新生儿中的天然管道，但在出生后不久关闭。在某些先天性心脏病 对于有缺陷的新生儿，保持导管通畅对于新生儿在没有外科干预的情况下生存至关重要。有 在美国没有市售的动脉导管支架。儿科介入心脏病专家目前 重新使用成人导管支架，全因导管再介入率为47%。另一种选择是开胸 在美国，对新生儿进行手术以放置分流管，其发病风险为13.1%，死亡风险为7.2%。 Starlight Cardiovascular提议创建并商业化第一个FDA批准的动脉导管支架 这是专门设计来解决面临的挑战治疗医生，包括正确的大小交付 系统、导管的端到端覆盖、通过迂曲导管解剖结构的导航和展开，以及 精确放置以避免支架突出到主动脉和肺动脉中。设计并测试的支架 专门用于这一目的的药物有可能减少再干预、发病率和潜在的死亡率， 依赖导管循环的婴儿创新的儿科支架系统的可行性 使用自扩展技术的应用在第一阶段通过许多 几轮实验室测试、医生评估和动物研究;这一第二阶段申请提出 最终确定支架设计并完成临床试验和FDA批准所需的临床前试验。 通过快速迭代，Starlight将开始优化支架系统的设计特征， 可制造性。然后，Starlight将在16只新生羔羊中完成一项长期GLP动物研究，以证明 180天内的支架通畅率。支架系统所有方面的验证和确认（V&V）试验（包括 生物相容性、灭菌和机械试验），然后将按照FDA指南进行 血管内支架的文件。该II期项目将最终形成动脉导管支架系统 已通过临床试验和后续FDA要求的所有必要临床前测试的设计 通过人道主义设备豁免途径获得批准。

ABSTRACT 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.