Standard Injections Versus Reduced Injections for Intravesical onabotulinumtoxinA Treatment of Overactive Bladder

Study Overview
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Brief Summary
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OnabotulinumtoxinA is an effective treatment for both idiopathic and neurogenic overactive bladder and was FDA approved for this indication in 2013. The standard technique for injecting onabotulinumtoxinA into the detrusor is mixing 100 units of onabotulinumtoxinA into 10mL of injectable normal saline and injecting 20 sites with 0.5mL in the posterior wall of hte bladder for idiopathic overactive bladder and mixing 200 units into 30mL and injecting 30 sites with 1mL for neurogenic overactive bladder. The purpose of this study is to compare the efficacy of a technique using a reduced number of injections with the same dosage of onabotulinumtoxinA to the standard technique. The hypothesis is that the reduced technique will not be inferior in terms of efficacy as the standard technique and that there will be a lower incidence of urinary tract infections and urinary retention requiring catheterization post-procedure.

Detailed Description
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Overactive bladder has a large economic burden within the United States and internationally. Patients are often non-compliant with first and second line treatments for overactive bladder or find that they do not significantly improve symptoms. Intradetrusor onabotulinumtoxinA injection has been showed in many studies to significantly improve overactive bladder symptoms and quality of life in patients and was approved by the FDA for the treatment of overactive bladder in 2013. Intradetrusor onabotulinumtoxinA injections are often performed in the office setting under local anesthesia. The standard technique for injecting onabotulinumtoxinA into the detrusor is mixing 100 units of onabotulinumtoxinA into 10mL of injectable normal saline and injecting 20 sites with 0.5mL in the posterior wall of hte bladder for idiopathic overactive bladder and mixing 200 units into 30mL and injecting 30 sites with 1mL for neurogenic overactive bladder. Despite instillation of local anesthetic into the bladder prior to the procedure, many patients still find the procedure uncomfortable and may elect not to have treatment or to undergo treatment under sedation. Some literature exists that suggests that a fewer number of injections with the same dosage of onabotulinumtoxinA still provides significant improvement in symptoms for patients with the potential for fewer adverse events, specifically urinary tract infection and urinary retention requiring catheterization. The purpose of this study is to directly compare the standard techniqe for intradetrusor onabotulinumtoxinA injections to a reduced injection technique to compare efficacy and rates of adverse events between the two groups. The hypothesis is that the reduced injection technique will be non-inferior to the standard technique. Participants in the study will be randomized to either the standard technique or the reduced technique at the time of their procedures, provided they meet the inclusion and exclusion criteria and provide written consent to participate. Efficacy will be measured using a series of validated patient questionnaires. Scores will be obtained at a baseline and then at two other time points post-procedure (4-12 weeks and 6-9 months). Rates of adverse outcomes, specifically urinary tract infection and urinary retention requiring catheterization, will also be obtained following the procedure. Other than the randomization of patients into study and control groups and having patients complete a series of questionnaires, the care of patients undergoing intradetrusor onabotulinumtoxinA injections will follow the standard of care. All patients will be screened for urinary tract infection prior to the procedure and if they screen positive will have their procedures delayed until after they are treated. All patients will receive pre-procedure antibiotics according to the American Urological Association guidelines. All patients will be screened for urinary retention and for symptoms of urinary tract infection at their initial post-procedure follow-up at 4-12 weeks and treated accordingly if they develop either.

Official Title
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Standard Injections Versus Reduced Injections for Intravesical onabotulinumtoxinA for Treatment of Idiopathic and Neurogenic Overactive Bladder: a Randomized Trial

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: onaBoNT-A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or Females ≥ 18 years of age Predominant complaint of urinary urgency, urinary frequency or urge incontinence Failed at least one medication (inadequate or poorly tolerated response) or behavior modification technique (timed voiding, pelvic floor physical therapy, etc.), or decline such interventions Willingness to perform self-catheterization in the event of symptomatic urinary retention Ability to follow study instructions and likely to complete all required follow-up Exclusion Criteria: Concurrent use of oral medications for treatment of OAB (anticholinergics or beta 3 agonists). Post void residual volume > 200 ml Symptomatic prolapse > POP-Q (Pelvic Organ Prolapse Quantification) stage 2 or greater that is untreated Evidence of active UTI (bladder infection) Any previous use of intradetrusor botulinum toxin (onabotulinumtoxinA or abobotulinumtoxinA) within the preceding 6 months Use of >/= 400 units bontulinum toxin in the preceding 3months in other areas of the body Procedure performed in the main operating room (not outpatient setting) Concurrent diagnosis of interstitial cystitis/painful bladder syndrome Females who are pregnant or planning a pregnancy during the study or who think that they may be pregnant at the start of the study, or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study. Any medical condition that may put the subject at increased risk with exposure to botulinum-A toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis/motor neuron disease, neuropathy, renal stones, or any other disorder that might interfere with neuromuscular function Known allergy or sensitivity to any of the components of onabotulinumtoxinA Concurrent participation in another investigational drug or device study that could impact the results Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study

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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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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Injections<br>For idiopathic overactive bladder, 100 units of onabotulinumtoxinA mixed in 10mL of injectable saline injected in 20 sites with 0.5mL per injection along the posterior wall of the bladder above the trigone. For neurogenic overactive bladder, 200 units of onabotulinumtoxinA mixed in 30mL of injectable saline injected in 30 sites with 1mL per injection along the posterior wall of the bladder above the trigone. | Drug: onaBoNT-A<br>* Intradetrusor onabotulinumtoxinA in either the standard number of injections or a reduced number of injections<br>* Other names: Botox;|
| Experimental: Reduced Injections<br>For idiopathic overactive bladder, 100 units of onabotulinumtoxinA mixed in 10mL of injectable saline injected in 5 sites with 2mL per injection in an X configuration on posterior wall of the bladder above the trigone. For neurogenic overactive bladder, 200 units of onabotulinumtoxinA mixed in 10mL of injectable saline injected in 5 sites with 2mL per injection in an X configuration on posterior wall of the bladder above the trigone. | Drug: onaBoNT-A<br>* Intradetrusor onabotulinumtoxinA in either the standard number of injections or a reduced number of injections<br>* Other names: Botox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in overactive bladder symptom severity and health related quality of life scores on the overactive bladder questionnaire short form | The overactive bladder questionnaire short form is a validated questionnaire assessing both symptoms and quality of life related to overactive bladder. The survey has two subscales, a health related quality of life scale and a symptom severity scale. Each subscale is scored separately with a range of 0 to 100. For health related quality of life a score of 0 indicates worst quality of life and 100 indicating best quality of life. For symptom severity, the scores also range from 0 to 100 but with higher scores indicating greater symptom severity and lower scores less symptom severity. | 4-12 weeks post-procedure | 
| Mean change from baseline in overactive bladder symptom severity and health related quality of life scores on the overactive bladder questionnaire short form | The overactive bladder questionnaire short form is a validated questionnaire assessing both symptoms and quality of life related to overactive bladder. The survey has two subscales, a health related quality of life scale and a symptom severity scale. Each subscale is scored separately with a range of 0 to 100. For health related quality of life a score of 0 indicates worst quality of life and 100 indicating best quality of life. For symptom severity, the scores also range from 0 to 100 but with higher scores indicating greater symptom severity and lower scores less symptom severity. | 6-9 months post-procedure | 
| Mean change from baseline in overactive bladder symptoms on the International Consultation on Incontinence Questionnaire short form | The International Consultation on Incontinence Questionnaire short form is a validated questionnaire assessing symptoms of overactive bladder and effect on quality of life. The scores range from 0 to 21 with higher scores indicating worse symptom severity and effect on quality of life. | 4-12 weeks post-procedure | 
| Mean change from baseline in overactive bladder symptoms on the International Consultation on Incontinence Questionnaire short form | The International Consultation on Incontinence Questionnaire short form is a validated questionnaire assessing symptoms of overactive bladder and effect on quality of life. Scores range from 0 to 21 with higher scores indicating greater symptom severity. | 6-9 months post-procedure | 
| Mean change from baseline in overactive bladder symptoms assessed with the Patient Global Impression of Severity and Improvement scores | The Patient Global Impression of Severity and Patient Global Impression of Improvement scores are validated single question surveys that assess patients' impression of the severity of their illness prior to treatment intervention and the degree of improvement following treatment intervention. The Patient Global Impression of Severity is a 4 point Likert scale ranging from 1 to 4 with 1 being normal and 4 being severe symptoms (mild and moderate completing the range of scores). The Patient Global Impression of Improvement is a 7 point Likert scale with 1 being very much better and 7 being very much worse (much better, a little better, no change, a little worse, and much worse completing the range of scores). | baseline, 4-12 weeks post-procedure and 6-9 months post-procedure | 
| Mean change from baseline in overactive bladder symptoms assessed with the Patient Global Impression of Severity and Improvement scores | The Patient Global Impression of Severity and Patient Global Impression of Improvement scores are validated single question surveys that assess patients' impression of the severity of their illness prior to treatment intervention and the degree of improvement following treatment intervention. The Patient Global Impression of Severity is a 4 point Likert scale ranging from 1 to 4 with 1 being normal and 4 being severe symptoms (mild and moderate completing the range of scores). The Patient Global Impression of Improvement is a 7 point Likert scale with 1 being very much better and 7 being very much worse (much better, a little better, no change, a little worse, and much worse completing the range of scores). | 4-12 weeks post-procedure | 
| Mean change from baseline in overactive bladder symptoms and incontinence episodes using patient reported pad counts and episodes of nocturia | Number of pads used for urge incontinence and nocturia episodes are frequent metrics used for assessing efficacy of overactive bladder treatments | 6-9 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of urinary tract infection | Urinary tract infection is a common complication from intradetrusor onabotulinumtoxinA treatment | 1 day to 12 weeks post-procedure | 
| Incidence of urinary retention requiring intermittent catheterization | Urinary retention is a common complication following intradetrusor onabotulinumtoxinA treatment | 2-6 weeks post-procedure | 
| Mean change in pain from baseline following intradetrusor onabotulinumtoxinA injection using visual analog scale | Visual Analog Scales are validated tools for assessing pain. The scale is scored from 0 to 10 with 0 being no pain and 10 being worst possible pain. | immediately post-procedure |