DUCTUS ARTERIOSUS STENT TO IMPROVE CONGENITAL HEART DEFECT MORTALITY

摘要 儿科心血管内科医生(外科医生和干预者)面临的技术挑战 长期以来一直被忽视，迫使他们使用为成年人和不同条件设计的设备来治疗疾病 有非常特殊的解剖学考虑的婴儿。其中一种情况是导管持续打开。 动脉：一种天然的管道，存在于所有新生儿身上，但在出生后不久就会关闭。在某些先天心脏 对于先天缺陷，保持导管通畅对于新生儿的存活至关重要，而无需手术干预。的确有 在美国还没有商用的动脉导管支架。目前的儿科介入心脏科医生 重新使用成人导管支架，所有原因引起的导管再干预率为47%。另一种选择是敞开胸膛 在美国，对新生儿进行分流手术的发病率为13.1%，死亡风险为7.2%。 星光心血管公司提议创造并商业化第一个FDA批准的动脉导管支架 这是专门为解决治疗医生面临的挑战而设计的，包括适当大小的分娩 系统，导管的端到端覆盖，通过曲折的导管解剖进行导航和部署，以及 精确放置，以避免支架突出进入主动脉和肺动脉。一种设计和测试的支架 特别是为了这个目的有可能减少再干预，发病率和潜在的死亡率 患有依赖导管循环的婴儿。为儿科设计新型支架系统的可行性 使用自扩展技术的应用程序在第一阶段成功演示，通过 几轮台架测试、医生评估和一项动物研究；这个第二阶段的应用程序提出了 最终确定支架设计并完成临床试验和FDA批准所需的临床前测试。 通过快速迭代，Starlight将从优化支架系统的设计特性和 可制造性。然后，Starlight将在16只新生羔羊身上完成一项慢性GLP动物研究，以证明 支架通畅期超过180天。支架系统所有方面的验证和确认(V&V)测试(包括 生物兼容性、灭菌和机械测试)然后将根据FDA的指导进行 血管内支架的文献。这一二期工程将最终形成动脉导管支架系统。 已通过临床试验和后续FDA所需的所有必要临床前测试的设计 通过人道主义装置豁免途径获得批准。

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.