Efficacy of Botulinum Toxin Type A for the Treatment of Non-neurogenic Urinary Urge Incontinence

• Sponsor: Saskatchewan Health Authority - Regina Area (Other)
• Overall Status: Completed
• CT.gov ID: NCT01226706
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 52
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Non-neurogenic urinary urge incontinence (UUI) is a common quality of life disorder that causes people to feel an "urgent" need to urinate. Standard treatment for UUI includes behavior modification, pelvic floor exercises, anticholinergic medication, and less commonly, sacral neuromodulation. Unfortunately anticholinergic therapy is only moderately effective.

Botulinum toxin A (BTA or Botox©) may be a useful treatment in patients that do not respond to standard therapy. Botulinum toxin A has been used in other studies to improve symptoms in neurogenic urinary incontinence, and a variety of lower urinary tract disorders. BTA has been used in other studies to improve the symptoms in urinary incontinence, migraines, spinal cord injuries and a variety of lower urinary tract disorders. However, the treatment of non-neurogenic urinary urge incontinence has not been examined in a well-controlled study.

The primary purpose of this study is to determine the efficacy of botulinum toxin A (BTA) in the treatment of non-neurogenic urinary urge incontinence (UUI). The secondary objectives are to examine the side effects associated with BTA treatment and the impact this treatment has on patients' quality of life.

Condition or Disease	Intervention/Treatment	Phase
Urinary Urge Incontinence	Drug: Botulinum Toxins, Type A; Drug: Placebos	N/A

Detailed Description

Introduction:

Non-neurogenic urinary urge incontinence (UUI) is a common quality of life disorder that becomes more prevalent with age. It is described as a condition that causes people to feel an "urgent" need to urinate due to muscle spasms in the bladder. Factors such as infection, inflammation, strokes, and dementia can stimulate the bladder to create spasms and cause urine loss. Overactive bladder refers to the symptom complex of urinary frequency, urgency and or nocturia with or without incontinence. Overactive bladder is a disorder of the storage phase of the bladder affecting approximately 16.9% of the US women, increasing to 31% after age 75. Standard treatment for UUI includes behavior modification, pelvic floor exercises, anticholinergic medication, and less commonly, sacral neuromodulation. Unfortunately anticholinergic therapy is only moderately effective and causes bothersome side effects, particularly at higher doses. Sacral neuromodulation therapy is currently unavailable in Saskatchewan with the closest treatment centre being located in Calgary.

Botulinum toxin A (BTA or Botox©) may be a useful treatment in patients that do not respond to standard therapy. Botulinum toxin A has been used in other studies to improve symptoms in neurogenic urinary incontinence, migraines following spinal cord injuries, and a variety of lower urinary tract disorders. This product has been approved by FDA for treatments of the following conditions: two eye muscle disorders (blepharospasm and strabismus in December 1989), severe underarm sweating (primary axillary hyperhydrosis), brow furrow and frown lines (April 2002) and other cosmetic purposes (July 2004). For the treatment of UUI, BTA is injected into the detrusor muscle of the bladder which is the muscle of the bladder that squeezes urine towards the outlet. BTA has been used in other studies to improve the symptoms in urinary incontinence and a variety of lower urinary tract disorders, however, the treatment for non-neurogenic urinary urge incontinence has not been examined in a well-controlled study.

Research Purpose and Objectives:

The primary purpose of this study is to determine the efficacy of BTA in the treatment of non-neurogenic UUI. The secondary objectives are to examine the side effects associated with BTA treatment and the impact this treatment has on patients' quality of life.

Research Methods:

This study employs a 12 month, double-blinded, randomized, partial cross-over design. The first 6 months of the study, subjects will be randomized to receive either detrusor injection of BTA or a placebo injection. In the remaining six months, subjects in the control group will be offered the detrusor injection of BTA. All 36 subjects will be followed for the remaining 6 months.

Study Procedures and Protocol

Pre-injection Assessment:

The pre-injection and assessment stage includes an evaluation of the medical history and physical exam. Previous therapy and medication will be disclosed to the physician. The investigator will ensure the subject meets the inclusion criteria, has had urinalysis and a pregnancy test if under 50 years old.

Day of the Procedure:

On the day of the surgery, the study pharmacist will randomize subjects using a random numbers table. The study doctor, nurses, and subjects will be blinded to treatment allocation. Ancef 1gm, or in the case of penicillin allergy, cipro 400 mg, will be given by intravenous.

A local anaesthetic will be instilled at the end of the cystoscopy (40 ml 1% lidocaine) and sedation will be provided as required. Fifteen minutes will lapse before beginning the procedure.

Using a 30 degree rigid scope and minimally invasive cystoscopic technique, 10 injections at 10 U/ml per injection (altogether 100 U of BTA) will be injected into the bladder wall, sparing the trigone.3,4 Subjects assigned to the placebo condition will receive injections of a saline at a similar frequency as the BTA injections.

Subjects will be observed for 60 minutes post procedure and then discharged home. This is the standard protocol for other BTA procedures performed on an outpatient basis in the RQHR. Catheter supplies will be provided upon discharge.

Follow-up Schedule:

1. Four to Six Weeks Post-Procedure: The primary and secondary measures will be assessed.

2. Three Months post-procedure: The same procedures will be repeated as at the four-to-six week assessment.

3. Six Months post-procedure: The four-to-six week assessment will be performed, and symptoms of retention or residual since the last visit will be discussed. A cystoscopy will be performed to study culture/urinalysis, measure desire and capacity, and show incontinence. Study allocation will be revealed at six months, and BTA injection will be offered to subjects that had received the placebo.

4. Nine Months: The four-to-six week procedures are repeated.

5. Twelve Months: The four-to-six week procedures are repeated.

Potential Significance:

Current anticholinergic therapy for non neurogenic UUI has limitations. In addition to significant systemic side effects, studies have shown that only 50% of patients improve with anticholinergic therapy, and that improvement does not always involve continence. Thus, detrusor injection of BTA may be a safe and efficacious therapy for patients who have failed standard therapy with anticholinergic medication and allow for an improved quality of life.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Botulinum Toxin A Intradetrusor Injections for the Treatment of Non-neurogenic Urinary Urge Incontinence- A Randomized Double-Blind Control Trial
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebos Placebo injected into the detrusor at Day 1,	Drug: Placebos; Placebos injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.
Experimental: Botulinum Toxins, Type A Botulinum Toxins, Type A 100U injected into the detrusor at Day 1	Drug: Botulinum Toxins, Type A; Botulinum Toxins, Type A 100U injected into the detrusor at Day 1

Outcome Measures

Primary Outcome Measures

1. Change in Maximum Capacity at Cystoscopy Between Baseline and 6 Month Follow-up [Baseline to 6 months]

   Cystoscopy is a test performed with a cystoscope, a narrow tube with a tiny camera at its tip, inserted into the urethra and bladder to see the inside of the bladder and urethra. Maximum bladder capacity--the amount of liquid or gas the bladder can hold under anesthesia. Without anesthesia, capacity is limited by either pain or a severe urge to urinate.

Secondary Outcome Measures

1. Change in Incontinence Episodes Between Baseline and 6 Week Follow-up [Baseline to 6 weeks]

   Incontinence- involuntary leakage of urine

2. Change in Incontinence Episodes Between Baseline and 3 Month Follow-up [Baseline to 3 month]

   Incontinence- involuntary leakage of urine

3. Change in Incontinence Episodes Between Baseline and 6 Month Follow-up [Baseline to 6 month]

   Incontinence- involuntary leakage of urine

4. Change in Incontinence Episodes Between Baseline and 9 Month Follow-up [Baseline to 9 months]

   Incontinence- involuntary leakage of urine

5. Change in Incontinence Episodes Between Baseline and 12 Month Follow-up [Baseline and 12 months]

   Incontinence- involuntary leakage of urine

6. Change in Incontinence Episodes Between Baseline and 24 Months Follow-up [Baseline and 24 months]

   Incontinence- involuntary leakage of urine

7. Change in Number of Daytime Voids Between Baseline and 6 Week Follow-up [Baseline to 6 weeks]

   Frequency of daily urination

8. Change in Number of Daytime Voids Between Baseline and 3 Month Follow-up [Baseline to 3 month]

   Frequency of daily urination

9. Change in Number of Daytime Voids Between Baseline and 6 Month Follow-up [Baseline to 6 months]

   Frequency of daily urination

10. Change in Number of Daytime Voids Between Baseline and 9 Month Follow-up [Baseline to 9 months]

    Frequency of daily urination

11. Change in Number of Daytime Voids Between Baseline and 12 Month Follow-up [Baseline to 12 months]

    Frequency of daily urination

12. Change in Number of Daytime Voids Between Baseline and 24 Month Follow-up [Baseline to 24 months]

    Frequency of daily urination

13. Change in Number of Night Voids Between Baseline and 6 Week Follow-up [Baseline to 6 weeks]

    Frequency of night voiding

14. Change in Number of Night Voids Between Baseline and 3 Month Follow-up [Baseline to 3 months]

    Frequency of night voiding

15. Change in Number of Night Voids Between Baseline and 6 Month Follow-up [Baseline to 6 months]

    Frequency of night voiding

16. Change in Number of Night Voids Between Baseline and 9 Month Follow-up [Baseline and 9 months]

    Frequency of night voiding

17. Change in Number of Night Voids Between Baseline and 12 Month Follow-up [Baseline to 12 months]

    Frequency of night voiding

18. Change in Number of Night Voids Between Baseline and 24 Months Follow-up [Baseline and 24 months]

    Frequency of night voiding

19. Subjective Benefit Assessment at 6 Weeks [Baseline to 6 weeks]

    Self assessed description of how well they believed the Botulinum Toxin type A was working. The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: dry (complete response), improvement (> 50% reduction in incontinence), partial response (≤ 50% reduction in incontinence), no response to treatment.

20. Subjective Benefit Assessment at 3 Months [Baseline to 3 months]

    Self assessed description of how well they believed the Botulinum Toxin type A was working. The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: dry (complete response), improvement (> 50% reduction in incontinence), partial response (≤ 50% reduction in incontinence), no response to treatment.

21. Subjective Benefit Assessment at 6 Months [Baseline to 6 months]

    Self assessed description of how well they believed the Botulinum Toxin type A was working.The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: dry (complete response), improvement (> 50% reduction in incontinence), partial response (≤ 50% reduction in incontinence), no response to treatment.

22. Change in Incontinence Impact Questionnaire From Baseline to 6 Weeks Follow-up [Baseline to 6 weeks]

    Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.

23. Change in Incontinence Impact Questionnaire From Baseline to 3 Months Follow-up [Baseline to 3 months]

    Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.

24. Change in Incontinence Impact Questionnaire From Baseline to 6 Months Follow-up [Baseline to 6 months]

    Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.

25. Change in Urogenital Distress Inventory From Baseline to 6 Week Follow-up [Baseline to 6 weeks]

    Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. Urogenital Distress Inventory - 6 (UDI-6) The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.

26. Change in Urogenital Distress Inventory From Baseline to 3 Months Follow-up [Baseline to 3 months]

    Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.

27. Change in Urogenital Distress Inventory From Baseline to 6 Months Follow-up [Baseline to 6 months]

    Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.

28. Change in Patient Perception of Bladder Condition From Baseline to 6 Weeks [Baseline to 6 weeks]

    Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.

29. Change in Patient Perception of Bladder Condition From Baseline to 3 Months [Baseline to 3 months]

    Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.

30. Change in Patient Perception of Bladder Condition From Baseline to 6 Months [Baseline to 6 months]

    Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.

31. Change in Indevus Urgency Severity Scale From Baseline to 6 Weeks [Baseline to 6 weeks]

    A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.

32. Change in Indevus Urgency Severity Scale From Baseline to 3 Months [Baseline to 3 months]

    A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.

33. Change in Indevus Urgency Severity Scale From Baseline to 6 Months [Baseline to 6 months]

    A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.

34. 24 Hour Pad Weight (gm) at 3 Months [3 months]

    weight of pad (in gm) worn for 24 hours to detect urine loss

35. 24 Hour Pad Weight (gm) at 9 Months [9 months]

    weight of pad (in gm) worn for 24 hours to detect urine loss

36. Frequency of Urinary Tract Infections From Baseline to 6 Months [Baseline to 6 months]

    Frequency of urinary tract infections from baseline to 6 month-follow-up

37. Frequency of Participants Needing Self-catheterization From Baseline to 6 Month Follow-up [Baseline to 6 months]

    Frequency of participants needing self-catheterization from baseline to 6 month follow-up.

38. Frequency of Participants With Urinary Tract Infections From Baseline to 6 Months [Baseline to 6 months]

    Frequency of particiapnts with urinary tract infections from baseline to 6 month-follow-up

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female subjects, greater than 17 years of age

• Written informed consent has been obtained

• Ability to follow study instructions and likely to complete all required visits

• Written authorization for Use and Release of Health and Research Study Information has been obtained

• Subject meets the following criteria: clinical diagnosis of urinary urge incontinence with resistance to or intolerance of anticholinergic medication

• Anticholinergic medications allowed

• Willingness and ability to use self-catheterization if necessary

Exclusion Criteria:

• Uncontrolled clinically significant medical condition other than the condition under evaluation

• Known allergy or sensitivity to any of the components in the study medication

• Females with a positive pregnancy test, or who are breast-feeding, planning a pregnancy during the study, who think that they may be pregnant at the start of the study

• Concurrent participation in another investigational drug or device study

• Treatment with botulinum toxin of any serotype for urological condition prior to enrolment in study (if applicable)

• Any medical condition that may put the subject at increased risk with exposure to botulinum toxin A including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disorder that might interfere with neuromuscular function

• 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

• Symptomatic urinary retention or post-void residual of >200ml

• Anticoagulation therapy within 3 days of injection procedure

• Familial bleeding disorder

• UUI secondary to neurologic disease

• Myasthenia gravis

• Previous bladder pathology (e.g. transitional cell carcinoma)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regina General Hospital	Regina	Saskatchewan	Canada	S4P 0W5

Sponsors and Collaborators

• Saskatchewan Health Authority - Regina Area

Investigators

• Principal Investigator: Corrine Jabs, MD, Saskatchewan Health Authority - Regina Area

Study Documents (Full-Text)

None provided.

More Information

Publications

• Coyne KS, Matza LS, Kopp Z, Abrams P. The validation of the patient perception of bladder condition (PPBC): a single-item global measure for patients with overactive bladder. Eur Urol. 2006 Jun;49(6):1079-86. Epub 2006 Jan 24.
• Kalsi V, Apostolidis A, Popat R, Gonzales G, Fowler CJ, Dasgupta P. Quality of life changes in patients with neurogenic versus idiopathic detrusor overactivity after intradetrusor injections of botulinum neurotoxin type A and correlations with lower urinary tract symptoms and urodynamic changes. Eur Urol. 2006 Mar;49(3):528-35. Epub 2006 Jan 6.
• Nixon A, Colman S, Sabounjian L, Sandage B, Schwiderski UE, Staskin DR, Zinner N. A validated patient reported measure of urinary urgency severity in overactive bladder for use in clinical trials. J Urol. 2005 Aug;174(2):604-7.
• Patki PS, Hamid R, Arumugam K, Shah PJ, Craggs M. Botulinum toxin-type A in the treatment of drug-resistant neurogenic detrusor overactivity secondary to traumatic spinal cord injury. BJU Int. 2006 Jul;98(1):77-82.
• Rajkumar GN, Small DR, Mustafa AW, Conn G. A prospective study to evaluate the safety, tolerability, efficacy and durability of response of intravesical injection of botulinum toxin type A into detrusor muscle in patients with refractory idiopathic detrusor overactivity. BJU Int. 2005 Oct;96(6):848-52.
• Sahai A, Kalsi V, Khan MS, Fowler CJ. Techniques for the intradetrusor administration of botulinum toxin. BJU Int. 2006 Apr;97(4):675-8.
• Sahai A, Khan MS, Dasgupta P. Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity: results from a single center, randomized, double-blind, placebo controlled trial. J Urol. 2007 Jun;177(6):2231-6.
• Schurch B, de Sèze M, Denys P, Chartier-Kastler E, Haab F, Everaert K, Plante P, Perrouin-Verbe B, Kumar C, Fraczek S, Brin MF; Botox Detrusor Hyperreflexia Study Team. Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. J Urol. 2005 Jul;174(1):196-200.
• Smith CP, Nishiguchi J, O'Leary M, Yoshimura N, Chancellor MB. Single-institution experience in 110 patients with botulinum toxin A injection into bladder or urethra. Urology. 2005 Jan;65(1):37-41.
• Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003 May;20(6):327-36. Epub 2002 Nov 15.
• Uebersax JS, Wyman JF, Shumaker SA, McClish DK, Fantl JA. Short forms to assess life quality and symptom distress for urinary incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program for Women Research Group. Neurourol Urodyn. 1995;14(2):131-9.
• Vo AH, Satori R, Jabbari B, Green J, Killgore WD, Labutta R, Campbell WW. Botulinum toxin type-a in the prevention of migraine: a double-blind controlled trial. Aviat Space Environ Med. 2007 May;78(5 Suppl):B113-8.

• Responsible Party: Corrine Jabs, Department Head Obstetrics & Gynecology, Saskatchewan Health Authority - Regina Area
• ClinicalTrials.gov Identifier: NCT01226706
• Other Study ID Numbers: REB-08-04; 120486
• First Posted: Oct 22, 2010
• Last Update Posted: Jul 3, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Corrine Jabs, Department Head Obstetrics & Gynecology, Saskatchewan Health Authority - Regina Area: Urinary incontinence, urge; detrusor hyperreflexia; detrusor instability; non-neurogenic; Female Urogenital Diseases and Pregnancy Complications; Female Urogenital Diseases; Urologic Diseases; Urination Disorders; Urinary Incontinence
• Additional relevant MeSH terms: Urinary Incontinence, Urge; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Period Title: Overall Study
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Botulinum Toxin Type A	Total
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1	Total of all reporting groups
Overall Participants	10	11	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (11.2)	63 (9.4)	63.38 (10.04)
Sex: Female, Male (Count of Participants)
Female	10 100%	11 100%	21 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	10 100%	11 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Change in Maximum Capacity at Cystoscopy Between Baseline and 6 Month Follow-up
Description	Cystoscopy is a test performed with a cystoscope, a narrow tube with a tiny camera at its tip, inserted into the urethra and bladder to see the inside of the bladder and urethra. Maximum bladder capacity--the amount of liquid or gas the bladder can hold under anesthesia. Without anesthesia, capacity is limited by either pain or a severe urge to urinate.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [mL]	-97.5 (176.92)	64.1 (105.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments	A sample of 16 subjects per group was required to detect a mean difference of 50 mL in maximum capacity at cystoscopy between botulinum toxin and placebo at 90% power with a two-sided type I error of 5%. Difference scores were computed for the primary outcome, which were then compared using the Wilcoxon- Mann-Whitney U test. This type of analysis was used to identify both between group differences and within group differences (over time) while using non-parametric statistics.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.016
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

2. Secondary Outcome

Title	Change in Incontinence Episodes Between Baseline and 6 Week Follow-up
Description	Incontinence- involuntary leakage of urine
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of episodes]	.50 (1.75)	3.00 (4.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.152
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

3. Secondary Outcome

Title	Change in Incontinence Episodes Between Baseline and 3 Month Follow-up
Description	Incontinence- involuntary leakage of urine
Time Frame	Baseline to 3 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of occurences]	1.28 (2.43)	5.05 (5.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

4. Secondary Outcome

Title	Change in Incontinence Episodes Between Baseline and 6 Month Follow-up
Description	Incontinence- involuntary leakage of urine
Time Frame	Baseline to 6 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [number of episodes]	-.39 (3.58)	4.09 (5.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.067
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

5. Secondary Outcome

Title	Change in Incontinence Episodes Between Baseline and 9 Month Follow-up
Description	Incontinence- involuntary leakage of urine
Time Frame	Baseline to 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of occurences]	-3.38 (2.43)	NA (NA)

6. Secondary Outcome

Title	Change in Incontinence Episodes Between Baseline and 12 Month Follow-up
Description	Incontinence- involuntary leakage of urine
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of occurences]	-3.83 (2.06)	-2.17 (5.02)

7. Secondary Outcome

Title	Change in Incontinence Episodes Between Baseline and 24 Months Follow-up
Description	Incontinence- involuntary leakage of urine
Time Frame	Baseline and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of occurences]	-3.75 (1.81)	-2.78 (7.55)

8. Secondary Outcome

Title	Change in Number of Daytime Voids Between Baseline and 6 Week Follow-up
Description	Frequency of daily urination
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	-0.50 (2.15)	2.14 (2.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

9. Secondary Outcome

Title	Change in Number of Daytime Voids Between Baseline and 3 Month Follow-up
Description	Frequency of daily urination
Time Frame	Baseline to 3 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	0.89 (2.55)	3.32 (3.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

10. Secondary Outcome

Title	Change in Number of Daytime Voids Between Baseline and 6 Month Follow-up
Description	Frequency of daily urination
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	-0.22 (2.39)	2.73 (2.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

11. Secondary Outcome

Title	Change in Number of Daytime Voids Between Baseline and 9 Month Follow-up
Description	Frequency of daily urination
Time Frame	Baseline to 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	-1.13 (1.69)	NA (NA)

12. Secondary Outcome

Title	Change in Number of Daytime Voids Between Baseline and 12 Month Follow-up
Description	Frequency of daily urination
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	-1.61 (1.85)	-1.67 (2.36)

13. Secondary Outcome

Title	Change in Number of Daytime Voids Between Baseline and 24 Month Follow-up
Description	Frequency of daily urination
Time Frame	Baseline to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	-0.33 (3.92)	-2.61 (2.85)

14. Secondary Outcome

Title	Change in Number of Night Voids Between Baseline and 6 Week Follow-up
Description	Frequency of night voiding
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	0.31 (1.31)	0.77 (1.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.904
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

15. Secondary Outcome

Title	Change in Number of Night Voids Between Baseline and 3 Month Follow-up
Description	Frequency of night voiding
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [Number of voids]	0.06 (1.29)	1.36 (1.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

16. Secondary Outcome

Title	Change in Number of Night Voids Between Baseline and 6 Month Follow-up
Description	Frequency of night voiding
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	0.33 (0.79)	1.32 (1.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.230
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

17. Secondary Outcome

Title	Change in Number of Night Voids Between Baseline and 9 Month Follow-up
Description	Frequency of night voiding
Time Frame	Baseline and 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [Number of voids]	-1.13 (1.03)	NA (NA)

18. Secondary Outcome

Title	Change in Number of Night Voids Between Baseline and 12 Month Follow-up
Description	Frequency of night voiding
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	-0.94 (1.16)	-1.28 (1.33)

19. Secondary Outcome

Title	Change in Number of Night Voids Between Baseline and 24 Months Follow-up
Description	Frequency of night voiding
Time Frame	Baseline and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [number of voids]	-0.72 (1.25)	-1.00 (1.35)

20. Secondary Outcome

Title	Subjective Benefit Assessment at 6 Weeks
Description	Self assessed description of how well they believed the Botulinum Toxin type A was working. The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: dry (complete response), improvement (> 50% reduction in incontinence), partial response (≤ 50% reduction in incontinence), no response to treatment.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [score on a 4-point rating scale]	3.4 (0.9)	2.4 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Subjective Benefit Assessment at 3 Months
Description	Self assessed description of how well they believed the Botulinum Toxin type A was working. The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: dry (complete response), improvement (> 50% reduction in incontinence), partial response (≤ 50% reduction in incontinence), no response to treatment.
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [score on a 4-point rating scale]	3.2 (0.9)	1.9 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Subjective Benefit Assessment at 6 Months
Description	Self assessed description of how well they believed the Botulinum Toxin type A was working.The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: dry (complete response), improvement (> 50% reduction in incontinence), partial response (≤ 50% reduction in incontinence), no response to treatment.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [score on a 4-point rating scale]	2.8 (0.9)	1.6 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.0 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change in Incontinence Impact Questionnaire From Baseline to 6 Weeks Follow-up
Description	Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [scores on a scale]	.00 (14.02)	27.27 (41.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.173
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

24. Secondary Outcome

Title	Change in Incontinence Impact Questionnaire From Baseline to 3 Months Follow-up
Description	Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	4.29 (15.30)	35.35 (41.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

25. Secondary Outcome

Title	Change in Incontinence Impact Questionnaire From Baseline to 6 Months Follow-up
Description	Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	3.81 (33.95)	34.63 (36.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

26. Secondary Outcome

Title	Change in Urogenital Distress Inventory From Baseline to 6 Week Follow-up
Description	Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. Urogenital Distress Inventory - 6 (UDI-6) The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	6.11 (15.37)	17.68 (30.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.557
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

27. Secondary Outcome

Title	Change in Urogenital Distress Inventory From Baseline to 3 Months Follow-up
Description	Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	15.33 (14.44)	32.32 (19.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

28. Secondary Outcome

Title	Change in Urogenital Distress Inventory From Baseline to 6 Months Follow-up
Description	Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	11.11 (23.57)	28.48 (17.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.132
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

29. Secondary Outcome

Title	Change in Patient Perception of Bladder Condition From Baseline to 6 Weeks
Description	Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	.20 (.79)	1.45 (1.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

30. Secondary Outcome

Title	Change in Patient Perception of Bladder Condition From Baseline to 3 Months
Description	Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	.50 (1.27)	1.82 (1.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.099
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

31. Secondary Outcome

Title	Change in Patient Perception of Bladder Condition From Baseline to 6 Months
Description	Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	.50 (1.43)	1.55 (1.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.132
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

32. Secondary Outcome

Title	Change in Indevus Urgency Severity Scale From Baseline to 6 Weeks
Description	A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	1.00 (0.88)	1.09 (1.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

33. Secondary Outcome

Title	Change in Indevus Urgency Severity Scale From Baseline to 3 Months
Description	A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	0.67 (1.0)	1.36 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.230
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

34. Secondary Outcome

Title	Change in Indevus Urgency Severity Scale From Baseline to 6 Months
Description	A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy	Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
Measure Participants	10	11
Mean (Standard Deviation) [summary score]	0.60 (0.97)	1.09 (.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

35. Secondary Outcome

Title	24 Hour Pad Weight (gm) at 3 Months
Description	weight of pad (in gm) worn for 24 hours to detect urine loss
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [gm]	413.30 (558.82)	141.18 (301.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

36. Secondary Outcome

Title	24 Hour Pad Weight (gm) at 9 Months
Description	weight of pad (in gm) worn for 24 hours to detect urine loss
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Mean (Standard Deviation) [gm]	64.11 (145.36)	110.63 (277.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Botulinum Toxin Type A
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.888
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	A Bonferroni correction (0.05/n) was used for multiple comparisons

37. Secondary Outcome

Title	Frequency of Urinary Tract Infections From Baseline to 6 Months
Description	Frequency of urinary tract infections from baseline to 6 month-follow-up
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Number [number of occurences]	4	6

38. Secondary Outcome

Title	Frequency of Participants Needing Self-catheterization From Baseline to 6 Month Follow-up
Description	Frequency of participants needing self-catheterization from baseline to 6 month follow-up.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Number [Participants]	0 0%	1 9.1%

39. Secondary Outcome

Title	Frequency of Participants With Urinary Tract Infections From Baseline to 6 Months
Description	Frequency of particiapnts with urinary tract infections from baseline to 6 month-follow-up
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Botulinum Toxin Type A
Arm/Group Description	Placebo injected into the detrusor at Day 1, Placebo: Placebo injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.	Botulinum toxin Type A 100U injected into the detrusor at Day 1 botulinum toxin Type A: Botulinum toxin Type A 100U injected into the detrusor at Day 1
Measure Participants	10	11
Count of Participants [Participants]	4 40%	6 54.5%

Adverse Events

Time Frame	Adverse events were monitored from baseline up to 12 months after intervention (at 4-6 weeks, 3 months, 6 months, 9 months and 12 months).
Arm/Group Title	Placebo		Botulinum Toxin Type A
Arm/Group Description	normal saline injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy		Botulinum toxin Type A 100U injected into the detrusor in 5 sites on each side of the bladder (1 mL at each site) during cystoscopy
All Cause Mortality
	Placebo		Botulinum Toxin Type A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Botulinum Toxin Type A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/11 (9.1%)
Cardiac disorders
Perioperative Cardiac Event (Takotsubo syndrome)	0/10 (0%)	0	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Botulinum Toxin Type A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		5/11 (45.5%)
Gastrointestinal disorders
Constipation	0/10 (0%)		1/11 (9.1%)
General disorders
Pain/Discomfort	2/10 (20%)		3/11 (27.3%)
Infections and infestations
Hematuria	1/10 (10%)		1/11 (9.1%)

Limitations/Caveats

Poor recruitment. Recruitment slowed significantly when newer anticholinergic medications became available. Those who were previously eligible for the study had darifenacin and solifenacin to try before considering botulinum toxin treatment.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.