Clinical evaluation of a compliant, degradable ureteral stent to reduce patient pain and improve tolerability

项目总结 肾结石在国内和世界范围内都是一个重大的健康问题，发病率 在过去的三十年里，由于饮食习惯和久坐不动，发病率不断上升 生活方式。输尿管支架是支持肾结石治疗的重要工具，但在过去的50年里 几年来，传统的不可降解的单卷曲或双卷曲设计要求 二次拔除程序。疼痛和不适很普遍，据报道，高达80%的患者， 其他患者的不便也是如此，例如尿失禁。润滑性涂料等方面的进展 更高的合规性材料并没有显著解决这些担忧，不幸的是，它 已确定这些传统支架是疼痛和不适的直接原因，而(1)支架植入 放置，以及(2)二次支架取出过程的结果。由于疼痛，近四分之四的患者 使用阿片类药物的比率远远高于未植入支架的患者。这些劣势 展示对新支架概念的需求。ADVA-Tec，Inc.开发了可降解的Uriprene® 输尿管支架设计用于暂时支持从肾脏到膀胱的引流，作为 肾结石治疗。Uriprene是一种复合管结构，它像其他 输尿管支架，但植入后会软化，最终降解为顺应性碎片，使其无效 自然而然地排尿。一项8名患者的先导性临床研究，以及几项临床前评估， 确认了Uriprene的安全性，初步评估支持Uriprene有能力解决 支架就位时疼痛和不适；乌里普林还消除了二次取出的需要 手术是造成疼痛和不适的另一个重要因素。这项SBIR提案的目标是 通过一项单一的研究来证明乌利普林的安全性、有效性、大小便失禁发生率和疼痛反应 ARM多点研究。这将通过客观的成果措施来实现，例如实验室和 放射学评估，包括记录的止痛药使用情况，以及通过主观评估 通过有效的问卷对患者的疼痛进行评分等措施。这项研究将跟踪87 患者通过30天的支架降解和自我消除窗口，以及长达90天后 必要时做手术。支架性能将根据已发表的历史记录进行统计评估 代表护理标准的控制措施。之前与FDA的沟通证实了我们的监管 路径，这项研究的成功完成将为提交乌里普林提供必要的支持 用于监管许可的可降解支架，从而将这一重要设备的进步推向市场。

PROJECT SUMMARY Kidney stones represent a significant health concern both domestically and worldwide, with incidence rates increasing over the past three decades due to the combination of dietary habits and sedentary lifestyle. Ureteral stents are an important tool to support kidney stone management, but for the past 50 years have not advanced beyond the traditional nondegradable single- or double-curl design requiring a secondary procedure for removal. Pain and discomfort is prevalent, reported for up to 80% of patients, as are other patient inconveniences, such as urinary incontinence. Advances such as lubricious coatings and higher compliance materials have not significantly addressed these concerns and unfortunately, it is established that these traditional stents are a direct cause of pain and discomfort while (1) the stent is in place, and (2) as a result of the secondary stent removal procedure. Due to pain, nearly 4 in 10 patients use opioid medications, a far higher rate than that of non-stented patients. These disadvantages demonstrate a need for new stent concepts. ADVA-Tec, Inc. has developed Uriprene®, a degradable ureteral stent designed to temporarily support drainage from the kidney to the bladder as a part of kidney stone management. Uriprene is a composite tubular structure that provides drainage like other ureteral stents, but softens after implantation and ultimately degrades into compliant pieces that void naturally with urination. An 8-patient pilot clinical study, as well as several pre-clinical evaluations, has confirmed the safety of Uriprene, and preliminary evaluations support the ability of Uriprene to address stent pain and discomfort while in place; Uriprene also eliminates the need for a secondary removal procedure, another significant contributor to pain and discomfort. The objective of this SBIR proposal is to demonstrate the safety, efficacy, incontinence rates, and pain response of Uriprene through a single arm multi-site study. This will be achieved through objective outcome measures such as laboratory and radiographic assessments, including recorded usage of pain medications, as well as through subjective measures such as patient-scored pain through a validated questionnaire. This study will follow 87 patients through the 30-day stent degradation and self-elimination window, and up to 90 days post- surgery as necessary. Stent performance will be statistically evaluated against published historical controls that represent the standard of care. Prior communication with FDA confirms our regulatory path, and successful completion of this study will provide the necessary support to submit the Uriprene degradable stent for regulatory clearance, thereby translating this important device advance to market.