First-In-Human Feasibility Trial of Break Wave - The Office-Based Lithotripsy Solution

意义：需要一种安全有效的基于办公室的肾结石碎石治疗。 肾结石很常见；它们影响着近10%的美国人口，而且患病率还在继续增长 与高血压、糖尿病和肥胖症等疾病并存。肾结石也是 美国最昂贵的泌尿系疾病；美国的医疗保健负担每年超过100亿美元。一个 这笔费用的很大一部分是由于大约100万次外科手术和20%-40%的 手术后的意外事件。这包括体外冲击波碎石术(SWL)，一种常见的 非侵入性手术干预和输尿管镜激光碎石术(URS)，这是一种常见的内窥镜手术。 两者都有5%或更高的严重不良事件风险，在美国，这两种程序都进行 在病人麻醉的情况下在手术室里。技术：SonoMotion正在开发一种基于办公室的 无创、无麻醉的肾结石和输尿管结石碎石液重新定义 数以百万计的人的护理标准。Break WaveTM(即BWL)是一种新的碎石方法，它 使用多周期、低幅度的超声波脉冲而不是冲击波来诱导结石骨折。这 该方法有可能减少受伤风险和程序并发症的发生率，以及 大大降低了程序时间和成本。此外，低幅度脉冲将排除对 麻醉，提供以办公室为基础的治疗方法。这也可能提供一个有吸引力的 主动监视障碍物的替代方案。初步数据：体外研究表明， Break Wave技术能够将最常见的人体结石粉碎成大小为 始终小于1毫米。在猪模型中进行的临床模拟表明，压力水平 碎石所需的压力低于导致肾脏损伤所需的压力水平。具体目标：目标1是 一项30名患者、前瞻性、开放标签、多中心、单臂第一人体可行性临床试验，以评估 Break Wave的安全性和有效性。出现上尿路结石的受试者将被招募 作为SWL的替代方案。疗效取决于结石通道、治疗后的低剂量CT 成像和二次程序的必要性；安全性应通过记录的事件进行评估 不良事件、术后成像、计划外医生/急诊室就诊。程序容忍度和 还将评估在多种压力水平和在没有麻醉的情况下的有效性。审判将是 在4个中心进行，以获得多位知名泌尿科医生的广泛反馈。 在整个试验过程中，SonoMotion将确定设备设计和程序调整，以提高安全性和 有效性，并在目标2中实施这些更改。目标2还将实施和测试扩展射束 宽度，以打破较大的石头，并适应更大的病人的活动。这笔赠款的结果将是 临床就绪系统，启动关键临床试验，以获得FDA监管部门的批准。

Significance: There is a need for a safe and effective office-based lithotripsy treatment for kidney stones. Kidney stones are common; they affect nearly 10% of the US population and the prevalence continues to grow in parallel with diseases such as high blood pressure, diabetes, and obesity. Kidney stones are also one of the most costly urologic diseases in America; the health care burden in the US exceeds $10 billion annually. A substantial portion of this cost is due to the approximately one million surgical interventions and 20-40% rate of unplanned post-surgical events. This includes extracorporeal shock wave lithotripsy (SWL), a common noninvasive surgical intervention, and ureteroscopy laser lithotripsy (URS), a common endoscopic procedure. Both have a 5% or greater risk of significant adverse events and, in the US, both procedures are conducted within a surgical suite with the patient anesthetized. Technology: SonoMotion is developing an office-based, non-invasive, and anesthesia free stone lithotripsy solution for kidney and ureteral stones to redefine the standard of care for millions of people. Break WaveTM (i.e. BWL) is a novel method of stone fragmentation that uses multi-cycle, low-amplitude pulses of ultrasound rather than shock waves to induce stone fracture. This approach has the potential to reduce the risk of injury and the rate of procedural complications, as well as significantly lower procedural time and cost. Furthermore, the low amplitude pulses will preclude the need for anesthesia, providing an office-based treatment method. This could also potentially provide an attractive alternative to active surveillance of an obstructing stone. Preliminary Data: In vitro studies have shown the Break Wave technology is capable of fragmenting most common human stones into fragment sizes that are consistently less than 1 mm. Clinical simulation conducted in a porcine model indicates the pressure levels required to break stones are below the pressure levels required to induce renal injury. Specific Aims: Aim 1 is a 30-patient, prospective, open-label, multi-center, single-arm First-In-Human feasibility clinical trial to assess the safety and effectiveness of Break Wave. Subjects presenting with upper urinary tract stones will be recruited as an alternative to SWL. Effectiveness is to be determined by stone passage, post-treatment low dose CT imaging, and the need for secondary procedures; safety is to be evaluated through the documented occurrences of adverse events, post-procedural imaging, unplanned physician/ED visits. Procedural tolerance and effectiveness will also be evaluated at multiple pressure levels and at reduced to no anesthesia. The trial will be conducted across 4 centers to derive a broad range of feedback across multiple well-established urologists. Throughout the trial, SonoMotion will identify device design and procedural adjustments to improve safety and effectiveness, and implement those changes in Aim 2. Aim 2 will also implement and test expanding the beam width to break larger stones and accommodate greater patient movement. The outcome of this grant will be a clinical-ready system to initiate a pivotal clinical trial for FDA regulatory approval.