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

Break Wave 的首次人体可行性试验 - 基于办公室的碎石解决方案

• 批准号: 9919546
• 负责人: Oren Levy
• 金额: $ 99.72万
• 依托单位: SONOMOTION, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9919546
• 关键词: Accident and Emergency department; Acute; Address; Adverse event; Affect; Aftercare; American; Americas; Anesthesia procedures; Animals; Chronic; Clinic; Clinical; Clinical Trials; Consensus; Cost of Illness; Data; Device Designs; Devices; Diabetes Mellitus; Disease; Dose; Effectiveness; Elements; Emergency Department Physician; Emergency department visit; Ensure; Event; Extracorporeal Shockwave Lithotripsy; Family suidae; Feasibility Studies; Feedback; Fracture; Frequencies; Goals; Grant; Healthcare; Histologic; Human; Hypertension; Image; In Vitro; Injury; Injury to Kidney; Intervention; Kidney; Kidney Calculi; Laser Lithotripsy; Lithotripsy; Methods; Modeling; Modification; Movement; Natural graphite; Obesity; Operative Surgical Procedures; Outcome; Patients; Performance; Physiologic pulse; Population; Prevalence; Procedures; Protocols documentation; Risk; Safety; Shock; System; Techniques; Technology; Testing; Time; Ultrasonography; Update; Ureteroscopy; Urinary Calculi; Urologic Diseases; Urologist; Urology; Visit; Width; X-Ray Computed Tomography; arm; base; care burden; cost; design; feasibility trial; first-in-human; human subject; imaging system; improved; in vivo; low dose computed tomography; novel; open label; preclinical safety; preclinical study; preclinical trial; pressure; prospective; recruit; simulation; standard of care; verification and validation

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.

意义：需要对肾结石进行安全有效的基于办公室的岩石疗法治疗。 肾结石很常见；它们影响了近10％的美国人口，并且患病率继续增长 与高血压，糖尿病和肥胖症等疾病并行。肾结石也是 美国最昂贵的泌尿科疾病；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一百万个手术干预措施和20-40％ 计划外术后事件。这包括体外冲击波岩石疗法（SWL），一种常见 非侵入性手术干预和输尿管镜激光碎石（URS），一种常见的内窥镜手术。 两者都有重大不良事件的5％或更高的风险，在美国进行了这两个程序 在手术套房中，患者麻醉了。技术：Sononotion正在开发基于办公室的， 肾脏和输尿管结石的无创和无麻醉的石材4s 数以百万计的人的护理标准。 Break Wavetm（即BWL）是一种新颖的石材碎片方法 使用超声波而不是冲击波的多周期，低振幅脉冲来诱导石材断裂。这 方法有可能降低受伤风险和程序并发症的速度，以及 程序时间和成本大大降低。此外，低振幅脉冲将排除在内的需求 麻醉，提供基于办公室的治疗方法。这也可能提供吸引力的 替代障碍石的主动监视。初步数据：体外研究表明 Break Wave Technology能够将大多数常见的人类石头分散成碎片大小 始终小于1毫米。在猪模型中进行的临床模拟表示压力水平 折断石头所需的压力水平低于诱发肾脏损伤所需的压力水平。具体目的：目标1是 一项30名受访者，前瞻性，开放标签，多中心，单臂第一臂可行性临床试验，以评估 断裂波的安全性和有效性。将招募带有上尿路石的受试者 作为SWL的替代方案。有效性将由石头通道，处理后低剂量CT确定 成像，以及需要进行辅助程序；安全将通过记录的事件进行评估 不良事件，后术成像，计划外的医师/ED访问。程序公差和 有效性还将在多个压力水平上评估，并降低至没有麻醉。审判将是 跨4个中心进行的，以获得多种良好的泌尿科医生的广泛反馈。 在整个试验中，Sononotion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中实施这些变化。AIM2还将实施和测试扩展光束 宽度可打破大石头并适应更大的患者运动。这笔赠款的结果将是 临床就绪系统启动了一项关键临床试验，以进行FDA监管批准。