RF Ablation of the Trigone for the Treatment of UUI

Study Overview
=================
Brief Summary
-----------------
The primary objective of this pivotal study is to collect data on the safety and effectiveness of the Hologic trigone RF ablation device to reduce urgency urinary incontinence. Up to 325 subjects will be enrolled with 225 randomized (2:1) and treated at up to 35 sites in the U.S. Additional sites in Canada, Australia, Europe, and other countries may also be considered. Sites outside of the U.S. cannot randomize more than 25% of subjects.

Detailed Description
-----------------
Up to 325 subjects who meet all inclusion and none of the exclusion criteria will be enrolled and up to 225 subjects will be randomized. Subjects will be randomized to either an active arm that includes treatment with the Hologic trigone RF ablation device, or a control arm who receive a sham procedure. With a 2:1 randomization, approximately 150 subjects will be treated with the Hologic trigone RF ablation device (treatment group) and 75 sham subjects treated with the sham procedure. Subjects will be blinded to their randomized treatment; however, due to the nature of the procedure, the treating investigator cannot be blinded to individual randomization assignments. Subjects who are randomized to the treatment arm will be followed at 2 weeks, 1 month, 3, 6, and 12 months and every 6 months thereafter. Subjects randomized to the sham arm will be followed through the 6-month visit. Follow up of all other subjects (cross-over and treatment arm) will conclude when the last subject in randomized treatment arm reaches their 12-month visit, is withdrawn, or is determined lost to follow-up.

Official Title
-----------------
Selective Bladder Denervation Using RF Energy for the Treatment of UUI

Conditions
-----------------
Urgent Urinary Incontinence

Intervention / Treatment
-----------------
* Device: selective bladder denervation using RF energy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-pregnant, non-lactating female NOTE: Females who are of childbearing potential must have had a negative pregnancy test <7 days prior to procedure and must be using medically accepted contraception or have a monogamous relationship with a partner who has undergone sterilization. Subject is ≥18 years of age Subject has a history of idiopathic UUI for ≥ 6 months Subject is willing to provide Informed Consent, is geographically stable, has the cognitive ability to complete the 3-day bladder diary and comply with the required diary, follow up visits and testing schedule requirements Ambulatory and able to use toilet without assistance Post-void residual (PVR) ≤ 150 ml Intolerant of, contraindicated for, or have failed drug therapy AND should not be on medications for their condition for at least 2 weeks prior Predominance of urgency urinary incontinence in subjects with mixed incontinence (mix of both stress and urgency incontinence) NOTE: Predominance is defined as having at least 2/3rds or 67% of reported incontinence as urgency urinary incontinence on the 3-day bladder diary, and a higher percentage urgency urinary incontinence score as compared to the SUI score on the MESA-UIQ Subject has not previously received, or did receive ≤ 100 units/intravesical treatment of Onabotulinum Toxin A (Botox®) for OAB and self-reports receiving benefit from Botox of normal durability (3-6 months), but discontinued or wishes to discontinue due to side effects, financial constraints, or required treatment regimen (e.g., treatment every 6 months) ≥ 4 episodes of urgency urinary incontinence (UUI) over 3-day Bladder Diary (an average of 1.33 UUI episodes/day) Exclusion Criteria: Planning on becoming pregnant during the 36-month study period Serum creatinine or BUN > twice the upper limit of normal within the last sixty days; Impaired renal function as measured by glomerular filtration rate (GFR) ≤ 65 Current bleeding disorder or coagulopathies Neurological disease affecting bladder function such as multiple sclerosis, spinal cord injuries, myasthenia gravis, Charcot-Marie-Tooth disease Subject has uncontrolled diabetes (HbA1C >8.5) documented in the last three months Subject is a chronic corticosteroid user defined as daily continuous use within the last 30 days Subject is critically ill or has a life expectancy <3 years Investigator determines that subject is not a suitable candidate for participation in an investigational clinical research study Post-surgical onset of de novo OAB Current hydronephrosis or hydroureter Patients with uninvestigated microhematuria Impaired voiding dysfunction due to underactive bladder or bladder outflow obstruction Current participation in any other interventional study. Participation in observational studies is permitted Prior or current diagnosis of polyuria or has a screening 3-day bladder diary with 24-hour total volume of > 3000 ml Urinary tract infection (UTI) that is not resolved or has not been treated with antibiotics for a minimum of 3 days at the time of procedure and has not been verified by a negative urinalysis Subject reports having, or has a documented history of ≥ 2 urinary tract infections (UTIs) in the last 6 months, or ≥3 UTIs in the last 12 months prior to enrollment Documented, spontaneous, unprovoked urinary retention requiring any type of catheterization within the last 6 months or retention in the past for which there was no diagnosis or definitive treatment Anatomical conditions that, in the opinion of the investigator, would preclude the introduction and/or use of the device Any prolapse at or beyond the hymen Subject has been diagnosed (at any time) with bladder cancer, interstitial cystitis or chronic pelvic pain syndrome Ureteral dysfunction, stricture or reflux including vesicoureteral reflux or a history of surgical treatment for vesicoureteral reflux Any abnormality of the urinary tract including the bladder, ureters or kidneys such as but not limited to: hydroureter, hydronephrosis, ureteric reflux, Hutch diverticulum, ureterocele, duplex system, ectopic ureter, unilateral renal agenesis, ectopic kidney, cross fused ectopia, or megaureter Any invasive or surgical intervention involving the kidneys, bladder, urethra, rectum or vaginal wall within the last 6 months (e.g., radiofrequency, implant, mid-urethral sling) Prior history of surgical mesh in the anterior vaginal compartment to treat pelvic organ prolapse History of complications with any transvaginal or mid-urethral implanted mesh Prior abdominal, pelvic or vaginal surgery that may have modified the structure or location of the bladder, ureters or urinary vasculature such as bladder reconstruction, retroperitoneal dissection or cross-trigonal ureteral implantation, urinary tract fistula repair Current use of OAB medications within the last 2 weeks OAB symptoms previously treated with a single injection of >100 units of Onabotulinum Toxin A (Botox®) OAB symptoms previously treated with Sacral Neuromodulation (SNM) and/or PTNS Previous pelvic irradiation Complete or total incontinence (i.e. the continuous or total loss of urinary control) Any functional incontinence (incontinence caused by a physical or mental impairment that keeps a subject from reaching the bathroom in time to urinate)

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

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects will be randomized to either the treatment with the Hologic trigone RF ablation device or a sham procedure. Randomization will occur in a 2:1 fashion (treatment: sham) meaning approximately 150 subjects will be treated with the Hologic trigone RF ablation device and 75 control subjects treated with the sham procedure. Randomization will be stratified by site.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RF Trigone Ablation Treatment Arm<br>A compatible standard cystoscopy lens (30°) will be inserted into the Hologic trigone RF Device. The bladder will be emptied of urine and saline infused into the bladder to allow adequate visualization and working space. Ablations at the trigone will be created using the Hologic trigone RF ablation device together with the compatible standard commercially available RF cannula and generator. It is expected that a subject would receive between 4-6 ablations to completely treat the appropriate area of the trigone. At the completion of the procedure, 200 ml of saline is instilled into the bladder to allow for assessment of voiding function prior to discharge. | Device: selective bladder denervation using RF energy<br>* RF ablation of the trigone for the treatment of UUI<br>|
| Sham Comparator: RF Trigone Ablation Sham Arm<br>The sham procedure will mimic the Hologic trigone RF ablation device procedure to maintain subject blinding and provide the most accurate assessment of control data while minimizing risk to the subject. The bladder will be emptied of urine and saline infused into the bladder to allow adequate visualization and working space. Suction will be applied to the bladder wall and the cannulas (needles) will be introduced into the bladder wall. Energy will not be delivered to the tissue when each sham ablation is started. In order to maintain blinding of the subject, the typical sounds that Hologic trigone RF ablation device makes during actual ablation/fulguration will be replicated. The simulated ablation procedure will be repeated as many times as necessary to cover the area of the trigone. 4 to 6 sham ablations would be required. At the completion of the procedure, 200ml of saline is instilled into the bladder to allow for assessment of voiding function prior to discharge. | Device: selective bladder denervation using RF energy<br>* RF ablation of the trigone for the treatment of UUI<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint | The proportion of UUI responders having a > 50% decrease in UUI episodes from baseline to 6-month follow-up as documented on the 3-day bladder diary. | 6 months | 
| Primary Safety Endpoint | All adverse events from randomized treatment through the close of the 12-month follow-up visit for subjects treated with the Hologic trigone RF ablation device. | 12 months |