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

项目摘要 肾结石在国内和世界范围内都是一个重大的健康问题， 在过去的三十年里，由于饮食习惯和久坐不动， 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， 多年来，没有超越传统的不可降解的单卷曲或双卷曲设计， 二次手术切除。疼痛和不适普遍存在，据报道高达80%的患者， 以及其它患者不便如尿失禁。润滑涂层等进步 和更高的合规性材料没有显着解决这些问题，不幸的是， 这些传统的支架是疼痛和不适的直接原因，同时（1）支架在 放置，和（2）由于二次支架取出手术。由于疼痛，近四成患者 使用阿片类药物，远高于非支架患者。这些缺点 证明了对新支架概念的需求。ADVA-Tec，Inc.开发了Uriprene®，一种可降解的 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是一种复合管状结构， 输尿管支架，但植入后软化，并最终降解成顺应性碎片， 自然排尿。一项8名患者的初步临床研究以及几项临床前评价， 证实了Uriprene的安全性，初步评估支持Uriprene解决以下问题的能力： 支架放置时的疼痛和不适; Uriprene还消除了二次取出的需要 这是导致疼痛和不适的另一个重要因素。本SBIR提案的目标是 通过单次试验证明Uriprene的安全性、有效性、尿失禁率和疼痛反应， arm多中心研究。这将通过客观的结果措施来实现，如实验室和 影像学评估，包括记录的止痛药使用情况，以及通过主观评估， 通过经验证的调查问卷进行患者疼痛评分等测量。本研究将于87 患者通过30天支架降解和自消除窗口，以及长达90天后， 必要时进行手术。将根据已发表的历史数据对支架性能进行统计学评价 代表护理标准的对照品。与FDA的事先沟通确认了我们的监管 路径，并成功完成这项研究将提供必要的支持，提交Uriprene 可降解支架的监管许可，从而将这一重要的设备推向市场。

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.