Acoustic Enhancer Research on Laser Lithotripsy (AEROLITH)

Study Overview
=================
Brief Summary
-----------------
A pivotal study to evaluate the safety and effectiveness of Applaud Acoustic Enhancer when used in conjunction with conventional ureteroscopic laser lithotripsy (URS-LL) in the treatment of subjects with urinary stones.

Detailed Description
-----------------
The AEROLITH Clinical Study will evaluate the safety and effectiveness of Applaud Acoustic Enhancer when used in conjunction with conventional ureteroscopic laser lithotripsy (URS-LL) in the treatment of subjects with urinary stones. The clinical study is a prospective, multi-center, two-arm, randomized, double blinded study. A total of 196 subjects will be enrolled in this study at up to 27 investigational sites located in the U.S.

Official Title
-----------------
Evaluation of Applaud Medical's Acoustic Enhancer With Laser Lithotripsy System in the Treatment of Urinary Stones

Conditions
-----------------
Urinary Stones

Intervention / Treatment
-----------------
* Device: Ureteroscopy Laser Lithotripsy (URS-LL) with Acoustic Enhancer
* Device: Standard Ureteroscopic Laser Lithotripsy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged ≥ 18 years to ≤ 75 years Provides written informed consent Patients with at least one urinary stone measuring 6mm or greater (but no more than a cumulative diameter of 20mm) located proximally to the iliac vessels on one side may be treated. Urinary stone(s) should be apparent on a CT scan within 60 days prior to study enrollment. Stone assessment will be conducted using CT imaging following CLIN-0025: AEROLITH IDE Study Screening Guide. Patients with bilateral stones are allowed but only one side may be treated. Only the treated side will be evaluated for safety and effectiveness Patients may enter the study with a stent in place. Patients presenting with absence of a Urinary Tract Infection as confirmed using urinalysis Exclusion Criteria: Patients with stones exceeding a cumulative diameter of 20mm on the side to be treated. Note: Punctate stones measuring ≤ 2mm do not count in the cumulative diameter limit. Patients with ureteral stones located distal to the iliac vessels on the side to be treated Diagnosis of radiolucent stones (on the side to be treated) on KUB or Scout CT Imaging For patients who have a ureteral stent in place, patient is excluded if stent is calcified or encrusted as verified using standard of care imaging (e.g. KUB X-ray) Patients who have had prior URS-LL within 3 months on the side to be treated at the time of consent. History of cystinuria Urine pH is < 5.5. Patients with known history of recurrent uric acid stones Untreated urinary tract infection (UTI) History of drug-resistant chronic UTI If female, pregnant as confirmed using urine test to be conducted on the day of the procedure. Patient has an American Society of Anesthesiologists (ASA) physical classification level of 4 or greater. Known sensitivity to possible medications used before, during, or after the URS Laser Lithotripsy procedure, including but not limited to the following: sedative agents, general anesthetics, topical anesthetics, and opioid analgesics Stones suspected in calyceal diverticula Horseshoe kidney Congenitally ectopic pelvic kidneys Full staghorn calculi >2cm Patients with elevated serum creatinine > 1.5mg/dl Patients with a solitary kidney Malrotated kidney on the side with urinary stone Duplicated collecting system or duplicated ureters Patients who are currently involved in any investigational drug or device trial or have been enrolled in such trials within 30 days of index procedure Patients who are actively taking antiplatelet and anti-coagulation except low dose aspirin Prostate biopsy within the last 3 months History of radiation therapy of abdomen and pelvis History of urinary tract reconstruction Other factors that the investigator feels would interfere with the participation and completion of the study such as: Inability to provide voluntary consent Inability to understand the clinical investigation or cooperate with investigational procedures Planned relocation or unable to return for required follow-up visits Vulnerable individuals (mentally disabled, physically disabled, prisoner, etc.)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a double blinded study in which study subjects will not be informed of their treatment allocation through the index procedure. In assessing stone fragmentation using a CT image as defined in the primary endpoint, an independent radiologist will conduct the assessment and will be blinded to the treatment allocation of each subject's CT image.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ureteroscopic Laser Lithotripsy with Acoustic Enhancer<br>Ureteroscopic Laser Lithotripsy with Acoustic Enhancer | Device: Ureteroscopy Laser Lithotripsy (URS-LL) with Acoustic Enhancer<br>* Applaud's Acoustic Enhancer is provided in a lyophilized form. After reconstitution, it is a liquid, containing micron-scale particles that are made of a perfluoroalkane gas core with a lipid shell. The device is intended to be used with cleared/approved pulsed laser systems in fragmenting urinary stones (calculi) in the upper (superior) pole, lower (inferior) pole, and interpolar region of the kidney, pelvis of the kidney, and proximal ureter.<br>|
| Active Comparator: Standard Ureteroscopic Laser Lithotripsy<br>Standard Ureteroscopic Laser Lithotripsy | Device: Standard Ureteroscopic Laser Lithotripsy<br>* Standard of care Ureteroscopic Laser Lithotripsy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Absence of or have residual fragments measuring less </= to 2 mm | Study subjects who present with a complete absence of stones, or have residual fragments measuring less than or equal to 2 mm on the treatment side, as assessed by CT imaging | At 30 days post index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Total Radiant Energy Used in the Treatment | Total radiant energy is defined as mean value of laser energy that will be measured for each study arm | At 30 days post index procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fragmentation of calcium-based urinary stones, Fragmentation of urinary stones