InSite for Over Active Bladder

Study Overview
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Brief Summary
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The purposes of this study are: To provide evidence from a randomized controlled trial that InterStim Therapy provides better relief of symptoms of OAB than standard medical treatments in current use. To fulfill the requirements of the FDA-mandated post-approval study of the safety of the tined lead using a minimally invasive approach.

Detailed Description
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Approximately 30 million Americans meet the criteria for overactive bladder (OAB). Urinary voiding dysfunction symptoms impose a significant physical and psychosocial impact on individuals, including loss of self-esteem and a decrease in the ability to maintain an independent lifestyle. These symptoms can substantially affect a subject's daily activities. Patients with OAB are managed with diet modification, bladder training or retraining, pelvic muscle rehabilitation, medication and biofeedback. Medications are used as the first-line therapy for urgency frequency and urinary urge incontinence. InterStim Therapy utilizes sacral nerve stimulation and is indicated in the US for the treatment of urinary retention and the symptoms of OAB, including urinary urge incontinence and significant symptoms of urgency-frequency alone or in combination, in subjects who have failed or could not tolerate more conservative treatments. InSite OAB Protocol 1634 consists of two phases; Phase I which is the randomized portion of the trail and Phase II the non-randomized portion. Phase 1: A minimum of 60 subjects randomized to InterStim and a minimum of 60 subjects randomized to SMT. Phase 2: Non-randomized, all qualified subjects will receive InterStim, approximately 297 enrolled Subjects previously enrolled in Protocol 1634 for Urinary Urge Incontinence and Protocol 1635 for Urgency-Frequency will be included in Phase I of the new Protocol 1634 of OAB.

Official Title
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Prospective, Multicenter Trial Evaluating the Safety and Efficacy of InterStim® Therapy in Subjects With Symptoms of Overactive Bladder (InSite OAB)

Conditions
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Urinary Incontinence, Urgency-frequency, Overactive Bladder

Intervention / Treatment
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* Device: InterStim
* Drug: Standard Medical Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of OAB including urinary urge incontinence or urgency-frequency Be male or female at least 18 years of age or older Be able to consent to participate by signing the Informed Consent Be willing and able to attend visits and comply with the study protocol including adequate operation of equipment Have failed or are not a candidate for more conservative treatment (e.g. pelvic floor training, biofeedback, behavioral modification) Have failed or could not tolerate (stopped taking medication due to lack of efficacy or intolerable side effects) at least one anticholinergic or antimuscarinic medication AND have at least one anticholinergic or antimuscarinic medication not yet attempted Have been on current regiment of OAB medications or have not been on any OAB medications, for at least 4 weeks prior to beginning the baseline voiding diary Exclusion Criteria: Have severe or uncontrolled diabetes or diabetes with peripheral nerve involvement Have concomitant medical conditions which would limit the success of the study procedure Have skin, orthopedic or neurologic anatomical limitations that could prevent successful placement of an electrode Have neurological diseases such as multiple sclerosis, clinically significant peripheral neuropathy or complete spinal cord injury (e.g., paraplegia) Have knowledge of planned MRIs, diathermy, microwave exposure, high output ultrasonic exposure, or RF energy exposure Have urinary tract mechanical obstruction such as benign prostatic hypertrophy, cancer, or urethral stricture Have symptomatic urinary tract infection (UTI) Have implantable neurostimulators, pacemakers, or defibrillators Have primary stress incontinence or mixed incontinence where the stress component overrides the urge component Have had treatment of urinary symptoms with botulinum toxin therapy in the past 12 months Be a woman who is pregnant or planning to become pregnant or are a woman of child-bearing potential who is not using a medically-acceptable method of birth control Have a life expectancy of less than one year Have plans to enroll in another investigation device or drug trial during their participation in this trial, or currently enrolled in an investigational device or drug trial

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>InterStim Therapy | Device: InterStim<br> <br> |
| Active Comparator: 2<br>Standard Medical Therapy | Drug: Standard Medical Therapy<br>* Oxybutynin 2.5mg, 5mg Oxybutynin extended release 5 mg, 10mg, 15mg Oxybutynin transdermal 3.9mg Solifenacin 5mg, 10mg Tolterodine 1mg, 2mg Tolterodine extended release 2mg, 4mg Trospium 20mg Darifenacin extended release 7.5mg, 15mg fesoterodine Fumarate 4mg, 8mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Randomized Cohort: OAB Therapeutic Response | To demonstrate that the OAB therapeutic response rate at 6 months is greater for the InterStim therapy group than for the Standard Medical Therapy group. OAB therapeutic response rate was calculated as number of subjects with OAB therapeutic response divided by number of subjects included in the analysis. OAB therapeutic response was defined as: at least 50% or greater improvement in average leaks/day from baseline for subjects with urinary incontinence at baseline or at least 50% improvement in average voids/day from baseline or a return to normal voiding frequency (<8 voids/day) for subjects with urgency-frequency at baseline. | 6 months | 
| All Implanted Cohort: Adverse Events Related to the Tined Lead That Require Surgery | To demonstrate that the upper bound of the 95% CI for the cumulative five-year rate of adverse events related to the tined lead that require surgery is less than 0.33. Adverse events on or after neurostimulator implant with an etiology of lead and with an intervention of surgical intervention/revision are the event of interest. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Implanted Cohort: Tined Lead Migration Rate | To estimate the suspected cumulative tined lead migration rate at 5 years in subjects with a full system implant. Suspected tined lead migration resulting in an adverse event of lead migration/dislodgement meets the definition of this endpoint. | 5 years | 
| All Implanted Cohort: Infection Rate Associated With the Tined Lead | To characterize the cumulative infection rate at 5 years associated with the tined lead in subjects with a full system implant. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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overactive bladder, urinary incontinence, incontinence,Urgency-frequency