A Bullet Proof vascular graft to prevent dialysis access cannulation injury

项目总结 仅在美国，终末期肾病(ESRD)就影响着超过75万人。血液透析 (HD)是一种用于肾功能衰竭患者的维持生命的疗法，需要抽血和 在透析机里循环。这一过程需要反复的针刺和随后的针 使用外科手术建立的血管分流系统。这些分流通常是通过将动脉连接到静脉来实现的。 使用人工合成管道(动静脉移植物[AVG])；这些移植物虽然被广泛使用，但 有很多缺点。首先，它们不允许立即插管，因为它们需要4个初始周期 植入后组织整合和愈合的数周时间。因此，超过85%的终末期肾病患者通过 在AVG愈合期间使用隧道透析导管(TDC)。因为tDCs与高发病率和 死亡率，植入后可立即插管的AVG的前景可能会降低 这些患者的发病率。其次，由于疏忽或插管不当而导致的HD通道损伤可能 导致移植物材料降解、假性动脉瘤形成、出血、血栓和感染。没有 目前可用的AVG可在植入后立即进行插管，有助于成功、防错 针头进入，防止插管损伤。为了减少这些并发症，InnAVasc Medical， Inc.已经开发出一种即刻进入的血液透析移植物，这种移植物被认为是为了确保常规的、成功的 插管，防止移植物损伤，因此，可以促进更安全的家庭HD；防弹血管移植物(BPG)。 这种移植物是由生物相容的材料建造的，设计为立即止血，自我封闭。 并防止意外的后部和侧壁针头穿透。在第二期项目中和早期可行性 临床研究，我们证实BPG可以成功地植入所有受试者，并且装置良好 被容忍了。此外，插管室按预期工作，以便能够立即进入并防止 与针头有关的伤害。然而，由于在软移植物到腔室的过渡中缺乏足够的应变缓解 早期移植物血栓发生率高于临床可接受水平。我们已经测试了修改后的 与原始的BPG相比，它在板凳上的移植物在管腔完整性的所有方面都优于原始的BPG。 此外，南美一项小型可行性研究的临床数据证实了新的菌株缓解 预防早期血栓形成。因此，我们有信心修订后的业务伙伴关系将会如预期般表现。 在下一次计划的临床研究中对功能、血流和通畅性进行评估。在这个IIB阶段，我们将进一步推动商业 开发修订后的BPG，并通过进行关键的临床试验来实现我们项目的具体目标 对终末期肾病患者HD治疗的安全性和有效性进行评价。这将是一个前瞻性的， 在美国七个地点进行的多中心、单臂临床研究，计划招收60名受试者 使用ESRD。510(K)申请将提交给美国食品和药物管理局，为期六个月 以患者随访为主要分析。

PROJECT SUMMARY End Stage Renal Disease (ESRD) affects more 750,000 individuals in the United States alone. Hemodialysis (HD) is a life-sustaining therapy for patients suffering from renal failure that requires blood to be withdrawn and cycled through a dialysis machine. This process requires repeated needle punctures and the consequent needle access to a surgically created vascular shunt. These shunts are often created by connecting an artery to a vein with a prosthetic synthetic conduit (arteriovenous graft [AVG]); these grafts, though widely used, suffer from many disadvantages. First, they do not allow for immediate cannulation as they require an initial period of 4 weeks for tissue incorporation and healing post implant. Thus, more than 85% of ESRD patients initiate HD via tunneled dialysis catheter (TDC) while their AVG heals. Because TDCs are associated with high morbidity and mortality rates, the prospect of an AVG that can be cannulated immediately post implantation may reduce morbidity in these patients. Second, HD access injuries caused by careless or poor cannulation practices can result in graft material degradation, pseudoaneurysm formation, bleeding, clots, and infections. There is no currently available AVG that offers immediate cannulation after implantation, facilitates successful, error-proof needle entry, and protects from access cannulation injury. To reduce these complications, InnAVasc Medical, Inc. has developed an immediate access hemodialysis graft that is deigned to assure routine, successful cannulation, prevents graft injury, and thus, could promote safer home HD; the Bullet Proof vascular graft (BPG). This graft is constructed of biocompatible materials and is designed to be immediately hemostatic, self-sealing and resistant to inadvertent posterior and sidewall needle penetration. In the Phase II project and early feasibility clinical study, we confirmed the BPG could be successfully implanted in all subjects and that the device was well tolerated. Furthermore, the cannulation chamber worked as intended to allow for immediate access and prevent needle-related injuries. However, due to a lack of adequate strain relief at the soft graft to chamber transition zones, there was a higher rate of early graft thrombosis than clinically acceptable. We have tested the revised graft on the bench compared to the original BPG and it outperforms the original in all aspects of luminal integrity. Furthermore, clinical data from a small feasibility study in South America confirmed the new strain relief prevented early thrombosis. Therefore, we are confident that the revised BPG will perform as expected in terms of function, flow, and patency in the next planned clinical study. In this Phase IIB, we will further the commercial development of the revised BPG and achieve our specific goal of the project by conducting a pivotal clinical study to evaluate its safety and effectiveness for HD access in subjects with ESRD. This will be a prospective, multicenter, single arm, clinical study conducted at seven sites in the US with a planned enrollment of 60 subjects with ESRD. A 510(k) application will be submitted to the US Food and Drug Administration with six months of patient follow-up as the primary analysis.