INTIBIA Pivotal Study

Study Overview
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Brief Summary
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Prospective, randomized, double-blind, multicenter study to evaluate the safety and efficacy of an implantable tibial nerve stimulator in subjects with urgency urinary incontinence (UUI).

Detailed Description
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All eligible subjects will be implanted with the INTIBIA device. Subjects will be randomized to either INTIBIA therapeutic or INTIBIA non-therapeutic in a 2:1 ratio for the first 3 months of the study, at which point all subjects will receive therapeutic stimulation. Subjects will complete voiding diaries and questionnaires at Baseline and prior to each follow-up visit, which will occur at Months 3, 6, 12, and 24. Subjects will be offered to keep the device or have it explanted at the end of the study.

Official Title
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A Prospective, Randomized Clinical Trial Evaluating INTIBIA, an Investigational Implantable Tibial Nerve Stimulator, Through 24-Months (INTIBIA Pivotal Study IU024)

Conditions
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Urinary Incontinence, Urge, Urinary Bladder, Overactive, Urinary Bladder Diseases, Urologic Diseases, Lower Urinary Tract Symptoms, Urological Manifestations

Intervention / Treatment
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* Device: INTIBIA Therapeutic
* Device: INTIBIA Non-Therapeutic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men 22-80 years of age Symptoms of overactive bladder with urgency urinary incontinence (UUI) demonstrated on a 72-hour voiding diary defined as a minimum of four (4) leaking episodes associated with urgency, and at least one leaking episode each 24-hour period Greater than or equal to 6-month history of UUI diagnosis Failure of conservative or behavioral therapy (e.g., bladder diet, timed voiding, bladder training, bladder control strategies, pelvic floor muscle training, fluid management) Willing to abstain from OAB medications for the duration of the study Willing to maintain a stable dose of all other medications that affect bladder function (e.g., tricyclic antidepressants) for at least four (4) weeks prior to beginning the baseline voiding diary and baseline questionnaires Ambulatory and able to use the toilet independently and without difficulty Willing and capable of providing informed consent Willing and able to complete all procedures and follow-up visits indicated in the protocol Exclusion Criteria: Diagnosis of stress urinary incontinence or mixed urinary incontinence, as confirmed by cough stress test and with a response of Yes to Q3 on the UDI-6 questionnaire Current symptomatic urinary tract infection (UTI), urethritis, or more than three (3) UTIs in past year Have post-void residual urine volume >30% of total voided volume Inadequate skin integrity or any evidence of an infection, edema or inflammation in either lower leg Evidence of anatomic abnormalities that could jeopardize the placement of the device or pose a hazard to the subject Prior treatment of urinary symptoms with nerve stimulation (e.g., percutaneous tibial nerve stimulation [PTNS] or sacral nerve stimulation [SNS]) History of chronic pain (e.g., chronic pelvic pain, fibromyalgia, Lyme disease, chronic back pain) An active implantable electronic device regardless of whether stimulation is ON or OFF Treatment of urinary symptoms with botulinum toxin therapy within twelve (12) months Any neurological condition that could interfere with normal bladder or tibial nerve function, including stroke, epilepsy, multiple sclerosis, Parkinson's disease, peripheral neuropathy, fibromyalgia, or spinal cord injury (e.g., paraplegia) Current urinary tract mechanical obstruction (e.g., benign prostatic enlargement or urethral stricture) Other urinary tract dysfunction (e.g., abnormal upper urinary tract function, vesicoureteral reflux, bladder stone or tumor, urinary fistula) End stage renal failure, GFR < 35, or dialysis History of pelvic cancer within the past two years Pelvic organ prolapse at or beyond the hymenal ring Interstitial cystitis or bladder pain syndrome as defined by either American Urological Association (AUA) or European Association of Urology (EAU) guidelines prior to INTIBIA implant date Diabetes with peripheral nerve compromise or uncontrolled diabetes Pregnant as confirmed by urine or serum pregnancy test, plans to become pregnant over the study period, is less than one-year post-partum, is breast-feeding Current active or a chronic systemic infection Condition requiring magnetic resonance imaging (MRI) of lower leg Condition requiring diathermy Allergy to polyethylene terephthalate, silicone rubber, platinum, iridium, or polyurethane Allergy to local anesthetic or adhesives Deemed unsuitable for enrollment by the investigator based on history or physical examination (e.g., bleeding disorders, current anticoagulant medications) Enrolled in another investigational or interventional device or drug trial over the study period

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All eligible subjects will be implanted with the INTIBIA device. Subjects will be randomized to either INTIBIA therapeutic or INTIBIA non-therapeutic in a 2:1 ratio for the first 3 months of the study, at which point all subjects will receive therapeutic stimulation.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INTIBIA Therapeutic<br>Implanted with INTIBIA device and programmed to therapeutic stimulation for the duration of the study. | Device: INTIBIA Therapeutic<br>* INTIBIA implantable tibial nerve stimulator with therapeutic stimulation<br>|
| Experimental: INTIBIA Non-Therapeutic<br>Implanted with INTIBIA device and programmed to non-therapeutic stimulation for the first 3 months, then to therapeutic stimulation for the duration of the study. | Device: INTIBIA Non-Therapeutic<br>* INTIBIA implantable tibial nerve stimulator with non-therapeutic stimulation for 3 months, then therapeutic stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | ≥50% reduction in UUI episodes between INTIBIA therapeutic and INTIBIA non-therapeutic | 3 Months | 
| Response Rate | ≥50% reduction in UUUI episodes in the INTIBIA therapeutic group | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urgency Score | Change in mean urgency score relative to baseline on a scale of 0 (no urgency) to 4 (urge incontinence) | 3 Months | 
| Daily Voids | Change in mean number of daily voids relative to baseline | 3 Months |