Safety and Effectiveness of the Ultrasonic Propulsion of Kidney Stones

This is an investigator initiated, NIH-funded study conducted by the University of Washington (UW). Our research group has developed a new, non-invasive technology using low intensity focused ultrasound to reposition kidney stones by imparting sufficient acoustic energy to physically move a stone. The focused ultrasound pulses are similar to pulses that may be used in elastography or acoustic radiation force imaging. Like conventional ultrasound, the probe is placed in contact with the patient's skin to image the stone following standard ultrasound imaging procedure. The same probe is then used to focus the ultrasound and apply a burst (a sequence of pulses) of acoustic force to push the stone. Brightness mode (B-mode) imaging is interleaved with the "pushing" pulses (Push-mode) to monitor stone movement. The user controls the burst amplitude. To limit heating at the probe surface, there is a slight delay before the operator can execute the next push.

In addition to undergoing the investigational procedure, the research activities include the following:

• subjects undergo a pain questionnaire before and after the procedure and report their current level of stone pain on a scale of 0 (no pain) to 10 (worst possible pain);
• the subject's skin in the area of probe placement is observed before and after the procedure;
• subjects are contacted once-a-week for 3 weeks to evaluate for potential adverse events, pain medication use, and, if applicable, stone passage;
• subjects are requested to undergo at least one follow-up imaging 4 - 12 weeks post-procedure;
• a review of each subject's medical records is conducted 90-days post-procedure to evaluate for additional effectiveness and safety events.
• Specifically for the residual fragment population (randomized control trial), subjects are contacted every 6 months for 3 years and their electronic medical record is reviewed for 5 years for stone growth, symptomatic, unscheduled medical visits, and surgery related to stones.

Subjects that qualify for the trial are recruited into different study arms (referred to as Population groups) based on their type of stone condition (de novo stone versus post-lithotripsy fragment), size of stone (≤ 5 mm or > 5 mm), and management plan (clinical observation or surgical intervention). The objectives vary based upon the Population group. Subjects may qualify for more than one population group and may undergo the investigational procedure up to 4 times total (inclusive of both the left and right-side urinary tracts). Subjects can only be enrolled in one population group at a time, there is a separate consent for each study population, and each study population is considered independent of the other groups. Recruitment into all population groups has been completed.

• First-in-Human Population: This was the initial group of subjects included under this clinical trial. This was a 15-subject feasibility study that included a broad range of populations. This feasibility population formulated the basis for expanding the trial into a larger study addressing each population separately. This is encompassed in subject populations 2-5 below.
• De Novo Small Stone Population: Subjects undergo the investigational procedure awake and in the clinic. To qualify the subject must have a de novo stone ≤ 5 mm in largest dimension. Ultrasonic propulsion is used with the intent to help facilitate stone passage. If the stone is larger than 5 mm, subjects could be recruited into the URS subject population (see bullet point #3 below).
• Concurrent with URS Population: Subjects undergo the investigational procedure while anesthetized and concurrently undergoing a ureteroscopy guided laser lithotripsy procedure (referred to herein as URS). To qualify the subject must have at least one stone ≤ 20 mm in the largest dimension and be scheduled for surgery. Ultrasonic propulsion may be used to move a de novo stone or stone fragments of varying sizes generated over the course of the URS procedure. Note that since these subjects are anesthetized, a pain questionnaire is not included as part of their protocol.
• Obstructing Stone Population: Subjects undergo the investigational procedure awake and in the clinic or emergency department (ED) setting. To qualify the subject must have clinical imaging confirmation of an obstructing stone with their pain managed and complete a urinalysis to for assess infection risk. Ultrasonic propulsion is used with the intent to relieve the obstruction and associated pain. A subset of subjects were exposed to higher amplitude dislodging pulses, in addition to the ultrasonic propulsion pulses.
• Residual Fragment Population: Subjects undergo the investigational procedure awake and in the clinic setting. To qualify the subject must have at least one post-lithotripsy residual fragment (≤ 5 mm in largest dimension) identified either on imaging or based on the investigator's interpretation of that imaging. This is a prospective, open-label, multicenter, randomized control trial (RCT) with a treatment arm and control arm. The only difference in protocol between the two arms is that only the treatment group undergoes the investigational procedure and the associated post-procedure pain questionnaire and the post-procedure skin surface inspection. Ultrasonic propulsion is used with the intent to demonstrate: a) the ability of the ultrasonic propulsion device to reposition stones within the human kidney, b) the subsequent clinical benefit of facilitating stone passage and reducing stone burden, and c) the subsequent clinical benefit of reducing relapse. This is the only population group recruited across more than one site - the UW and the VA Puget Sound Healthcare System.

Inclusion criteria

• Individuals suspected of having at least one kidney stone. This includes:

• Patients who are being managed with watchful waiting or medical therapy
• Patients who recently (but > 4 weeks) underwent lithotripsy treatment of their stones
• Patients scheduled for lithotripsy treatment

Or

• Individuals suspected of having an obstructed stone. This includes:

• Patients presenting with renal colic
• Patients presenting with hydronephrosis or dilation of the ureter

Primary Exclusion Criteria for all groups:

• Individuals under 18 years of age
• Individuals with non-echogenic stones
• Individuals unable or unwilling to comply with the follow-up requirements
• Individuals with a coagulation abnormality or taking blood thinners or other anticoagulant at clinically significant levels
• Individuals with mobility issues who are unable to comfortably lie for up to 30 minutes or roll from their back to their side
• Individuals belonging to a vulnerable group (pregnant, mentally disabled, physically disabled, prisoner, etc.)
• Individuals who have already received four previous ultrasonic propulsion procedures.
• Individuals who have received an ultrasonic propulsion treatment within the last 4 weeks.

Additional Exclusion Criteria for Obstructing Stone population

• Individuals with a suspicion of kidney infection or exhibiting signs of sepsis
• Individuals whom the treating physician considers to be at high risk for serious alternate diagnoses such as acute infectious etiologies (e.g. cholecystitis, appendicitis), aortic aneurysm and rupture, or bowel disorders.
• Individuals who have undergone renal transplant, or individuals who will undergo dialysis.
• Individuals with bilateral hydronephrosis
• Individuals with a single kidney
• Individuals who have already received an ultrasonic propulsion investigative treatment for the same obstructing stone