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

意义：需要一种安全有效的办公室碎石治疗肾结石。

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.