Improvement and validation of the Spring System for Permanent Relief of Urinary Obstruction related to Benign Prostatic Hyperplasia (BPH)

摘要 良性前列腺增生症(BPH)是梗阻性下尿路症状的最常见原因 男人。随着年龄的增长，前列腺逐渐增大，它会阻碍尿液从膀胱流出，导致 尿路劳损、尿频、尿急和夜尿。在Zenflow，我们开发了Spring系统，该系统 由单丝镍钛(镍钛)线圈植入，旨在永久缓解BPH相关的尿液 一种灵活的经尿道给药系统，包括带有内置可视化的膀胱镜。我们 开发此解决方案以满足长期的临床需求，即安全、高效、经济实惠、基于办公室的 前列腺增生症治疗，在单一程序中提供持久的症状缓解，没有副作用。该设备旨在 改进以前的技术，如支架和前列腺尿路提升装置。2014年至 2017年，我们开发了第一代Spring系统，并成功完成了包括 身体和慢性动物研究，然后是第一个人的研究。2017年，我们获得了NIH第二阶段SBIR 格兰特。该项目涉及改进设计以提高临床安全性、有效性和易用性。 有什么用。这个第二阶段项目的目标是，结合正在进行的试点临床试验，准备Zenflow 为美国的Pivotal IDE研究。虽然这个项目的目标是成功的，但临床测试揭示了机会 关于对Spring系统的进一步改进，我们相信这将导致更安全和更可靠的 手术在有效性上达到了一个新的前沿，也将扩大解剖学的范围 系统可以处理的配置。这些改进分为两个类别，我们将在这两个类别下进行测试 目前的拨款建议：在具体目标1中，我们将改进种植体和输送系统，以产生更多 有效的程序，可以治疗更广泛的患者，并在特定的目标2，我们将改进我们的 专利一次性膀胱镜，实现更好的可视化，并允许泌尿科医生将植入物放置更多 准确而自信地。接下来，在具体目标3中，我们将验证上述所有改进，我们将 在身体上测试完整的Spring系统，以演示Spring系统在模拟使用中的功能 泌尿科医生。该系统将在完成所有植入和交付后的第一年年底在两具身体上进行测试 目标1中描述的系统工作，然后在第2年末完成所有范围开发后再进行两次 目标2.这两项研究的成功完成，将标志着我们第二阶段工作的完成。我们会 将AIM 1植入工作的结果纳入我们的美国Pivotal IDE研究。目标2范围改进 将被纳入以后的临床研究中。虽然我们专门开发了Spring作用域，以将 弹簧植入物，它可以用于部署植入物，以治疗尿路狭窄或 痛性膀胱综合症、药物或能量输送治疗BPH相关的下尿路结石、前列腺癌或其他 条件。我们将继续探索这些可能性，并就替代应用提交知识产权申请。

ABSTRACT Benign Prostatic Hyperplasia (BPH) is the most common cause of obstructive lower urinary tract symptoms in men. As the prostate progressively enlarges with age, it obstructs the flow of urine from the bladder, leading to urinary straining, frequency, urgency, and nocturia. At Zenflow, we have developed the Spring System, which consists of a single-wire nickel titanium (nitinol) coil implant designed to permanently relieve BPH-related urinary obstruction, and a flexible transurethral delivery system that includes a cystoscope with built-in visualization. We developed this solution to meet the long-standing clinical need for a safe, effective, cost-efficient, office-based BPH therapy that provides durable symptom relief in a single procedure without side effects. The device aims to improve upon previous technologies such as stents and the prostatic urethral lift device. Between 2014 and 2017, we developed the first-generation Spring System and successfully completed preclinical work including cadaver and chronic animal studies, then first-in-man studies. In 2017, we were awarded a Phase II NIH SBIR grant. This project involved development of a refined design to improve clinical safety, effectiveness, and ease of use. The goal of this Phase II project was, in conjunction with ongoing pilot clinical trials, to prepare Zenflow for a US pivotal IDE study. While the aims of this project were successful, clinical testing revealed opportunities for further improvements to the Spring System, which we believe will result in an even safer and more reliable procedure that reaches a new frontier in effectiveness, and will also expand the range of anatomical configurations that the system can treat. These improvements fall into two categories which we offer to test under the current grant proposal: in Specific Aim 1 we will improve the implant and delivery system to yield a more effective procedure that can treat a broader range of patients, and in Specific Aim 2 we will improve our proprietary single-use cystoscope to enable better visualization and allow urologists to place the implant more accurately and confidently. Next, in Specific Aim 3 we will validate all improvements described above, we will test the full Spring System in cadavers to demonstrate functionality of the Spring System in simulated use by a urologist. The system will be tested on two cadavers at the end of year 1 after completing all implant and delivery system work described in Aim 1, then two more at the end of year 2 after completing all scope developments in Aim 2. Successful completion of both of these studies will represent completion of our Phase II work. We will incorporate the results of the Aim 1 implant work into our US pivotal IDE study. The Aim 2 Scope improvements will be incorporated into later clinical studies. While we developed the Spring Scope specifically to place the Spring Implant, it could be used for deployment of implants to treat conditions such as urethral strictures or painful bladder syndrome, delivery of drugs or energy to treat BPH-related LUTS, prostate cancer, or other conditions. We will continue to explore these possibilities and file intellectual property on alternative applications.