Intradetrusor Botulinum Toxin A for OAB Via 1 Versus 10 Injections: A Randomized Clinical Trial

Study Overview
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Brief Summary
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Patients with either overactive bladder (OAB) or urgency urinary incontinence (UUI) with be randomized (like a flip of a coin) to receive 100 units of bladder Botox® at either one injection site or ten injection sites. Efficacy and patient satisfaction will be measured by questionnaires.

Detailed Description
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Intradetrusor (bladder) Botulinum toxin A (BTA or Botox®) is a well-established treatment for urinary urgency incontinence (UUI).[1,2] While this treatment's efficacy in comparison to alternative therapies including anticholinergic medications and sacral neuromodulation for treatment of UUI has been studied, the ideal number of injection sites within the bladder has not been well established. [3,4] Intradetrusor BTA injections are often completed as an office procedure while the patient is awake. Each injection site can cause discomfort for the patient during the procedure. Urinary tract infection and urinary retention are risks associated with this procedure and could potentially be related to number of injection sites. Currently, there is a lack of information in the literature regarding the optimal number of intravesical BTA injection sites. Prior studies evaluated efficacy using 100u BTA spread across 20 injections sites, however current practices at local institutions safely use 10 injections sites based on studies showing similar effect and adverse event profiles between use of 10, 20, and 40 injection sites.[5,6] Research using animal models has shown diffuse distribution of BTA within the entire detrusor muscle after just a single BTA injection at one site.[7] This has been corroborated in human studies.[8] A recently published observational pilot study shows promise for single site intradetrusor Botox® injection as it reported a lower rate of urinary retention and similar durability.[9] Similar clinical efficacy with only one to three intravesical BTA injection[s] has also been reported.[10] In this study, participants will be randomized to receive 100u BTA via intradetrusor injection at one injection site (experimental) versus 10 injection sites (control). Investigators hypothesize that one injection will have similar efficacy to multiple injections and potentially better tolerability and patient satisfaction, due to decreased procedure time and less pain, along with potential for lower adverse event rates, specifically urinary retention and urinary tract infections.

Official Title
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Intradetrusor Botulinum Toxin A for OAB Via 1 Versus 10 Injections: A Randomized Clinical Trial

Conditions
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Overactive Bladder, Urinary Urge Incontinence, Overactive Bladder Syndrome, Urinary Incontinence, Urge, Urge Incontinence, Urinary Urgency, Urinary Frequency

Intervention / Treatment
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* Drug: OnabotulinumtoxinA 100 UNT [Botox]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female 18 years old or greater Diagnosis of overactive bladder (urinary urgency or frequency, OAB) or urinary urgency incontinence (UUI) Exclusion Criteria: Have a diagnosis of neurogenic bladder Received intravesical botox injections within prior 6 months Current treatment with either: SNM, PTNS, or OAB medications - need wash out as below SNM - turn device off for at least 2 weeks prior to procedure, off during 3-month follow up window PTNS - no treatments within 2 weeks of start, none during 3-month post-procedure follow up window OAB meds - 2 week wash out period prior to injection, none during 3-month post-procedure follow up window Currently pregnant or trying to get pregnant Contraindications to Botox® - hypersensitivity to Botox®, inability to self-catheterize/refusal to have indwelling catheter Have a UTI (can enroll after treatment) Have urinary retention (PVR>150cc on two occasions) Do not speak English or Spanish

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Parallel study with 2 arms, 1:1 randomization
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Injection Site<br>100u Botox® injected at one intradetrusor site | Drug: OnabotulinumtoxinA 100 UNT [Botox]<br>* Intradetrusor (Bladder) Botox Injection at 1 vs 10 injection sites<br>|
| Active Comparator: 10 Injection Sites<br>100u Botox® injected at 10 intradetrusor sites | Drug: OnabotulinumtoxinA 100 UNT [Botox]<br>* Intradetrusor (Bladder) Botox Injection at 1 vs 10 injection sites<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Overactive Bladder Questionnaire Long Form Score (symptoms severity sub-scale)(OAB-Q LF) | Participants will be asked to Overactive Bladder Questionnaire Long Form prior to receiving the Botox procedure. The OAB-Q LF symptom severity sub-scale score will be compared prior to procedure and again to score at 3 weeks after procedure. The OAB-q Symptom Severity Score will be computed at baseline and 3 weeks (and 3 months) using the standard scoring algorithm. Minimum value of symptom severity subscale is 8, maximum is 48. A higher score means worse symptoms. A lower score means less symptoms. | change from baseline OAB-Q score to 3 wk post-procedure score | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Overactive Bladder Questionnaire Long Form Score (symptoms severity sub-scale)(OAB-Q LF) | Participants will be asked to complete Overactive Bladder Questionnaire Long Form prior to receiving the Botox procedure. The OAB-Q LF symptom severity sub-scale score will be compared prior to procedure and again to score at 3 months after procedure. The OAB-q Symptom Severity Score will be computed at baseline and 3 weeks (and 3 months) using the standard scoring algorithm. Minimum value of symptom severity subscale is 8, maximum is 48. A higher score means worse symptoms. A lower score means less symptoms. | comparison of baseline OAB-Q score to 3 month post-procedure score | 
| Post-void residual (PVR) | A PVR will be collected via either urethral catheterization or bladder scan (ultrasound in clinic) at 3 weeks post-procedure as a marker of urinary retention. The PVRs will be compared between study and control groups | PVR collected at 3 wk post-procedure | 
| Number of participants with urinary tract infection (UTI) | Urine culture will be sent for any patient with urinary tract infections symptoms (eg: worsening urgency, frequency, dysuria). | anytime after procedure, until at least 3 months post-procedure. | 
| Patient Global Impression - Improvement (PGI-I) | Participants will complete PGI-I Questionnaire at 3 months after procedure. The minimum value is 1 (very much better) and maximum value score is 7 (very much worse). A higher score indicates worse symptoms. A lower score indicates better symptoms or more improvement. | 3 months after botox procedure | 
| Visual Analogue Scale (VAS) - Pain | Participants will complete VAS-pain immediately post-procedure as a pain and tolerability assessment | immediately after procedure |