Refractory Overactive Bladder: Sacral NEuromodulation v.... | NCT01502956

NCT01502956

ID	Type	Description	Link
U01HD069031	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Name	Class
Duke University	OTHER
University of Alabama at Birmingham	OTHER
University of California, San Diego	OTHER
The Cleveland Clinic

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
InterStim® device	Active Comparator	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.	Device: InterStim® device
Botox® injection	Active Comparator	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.	Drug: Botox® injection

Interventions

Name	Type	Description	Arm Group Labels	Other Names
InterStim® device	Device	Eligible subjects will complete baseline assessments, be randomized and scheduled for first stage lead placement (FSLP) InterStim®. The criterion for an initial clinical response to InterStim® therapy will be defined as a ≥50% improvement in the mean number of UUIE/day on a minimum 3 day bladder diary, completed during the 7-14 days following the first stage lead placement (FSLP). Subjects with a ≥ 50% improvement mean number of UUIE/day will be eligible to proceed with implantation of the implantable pulse generator (IPG). Subjects will then be followed monthly to determine the response to therapy.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Urge Urinary Incontinence (UUI) Episodes	The primary outcome is the change from baseline in mean number of UUI episodes over the first 6-month visit period (1, 2, 3, 4, 5 and 6 month assessments); and is measured using 3-day bladder diaries administered monthly for the first 6 month visit period.	6 Months

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Improvement of Bladder Function and Urinary Leakage	Proportion of subjects who report adequate improvement of their bladder function and urinary leakage with the Patient Global Impression of Improvement Questionnaire (PGI-I) at 6 months. Adequate improvement is defined as a rating of 1, 2, or 3 (better) on the patient-reported measure of perceived improvement with treatment on a scale of 1 (very much better) to 7 (very much worse).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Non-pregnant adult female at least 21 years old, with no plans to become pregnant during the course of the trial) and if of child-bearing potential, with a negative pregnancy test, and if sexually active, must be using medically acceptable contraception.
6 urge urinary incontinence episodes on a 3-day baseline bladder diary, with these urge incontinence episodes representing greater than 50% of the total incontinent episodes recorded.
Willing and able to complete all study related items and interviews.
Refractory urinary urge urinary incontinence: defined as (1) Persistent symptoms despite at least one or more conservative treatments (e.g. supervised behavioral therapy, supervised physical therapy); and (2)Persistent symptoms despite the use of a minimum of two anticholinergics, or unable to tolerate medication due to side effects, or has a contraindication to taking anticholinergic medication.
Currently not on an anticholinergic or antimuscarinic medication (e.g. oxybutynin, tolterodine, and/or fesoterodine) or be willing to stop medication for 3 weeks prior to completing baseline bladder diary and expected to remain off medications through duration of study.
Demonstrates ability (or have caregiver demonstrate ability) to perform clean intermittent self-catheterization.
Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function.
Urodynamic assessment within the previous 18 months prior to enrollment or done after enrollment, prior to randomization.

Exclusion Criteria:

Neurologic diseases such as multiple sclerosis, Parkinson Disease, CVA within 6 months prior to enrollment, myasthenia gravis, Charcot-Marie-Tooth disease, clinically significant peripheral neuropathy, and complete spinal cord injury.
Untreated urinary tract infection (UTI).
Any prior use of either study therapy for treatment of urinary urge incontinence (Botox A® or Interstim®).
Current participation in any other conflicting interventional research study.
PVR >150 ml on 2 occasions within 6 months prior to enrollment (If the PVR value was obtained by ultrasound and was ≥150 ml, the PVR will be confirmed by catheterization which will be the gold standard)
Subjects with knowledge of planned MRIs or diathermy, except those allowable per Medtronic guidelines.
Current or prior bladder malignancy.
Surgically altered detrusor muscle, such as augmentation cystoplasty.
Subjects taking aminoglycosides.
Currently pregnant or lactating.
Subjects who are on ambulatory anticoagulant therapy, including aspirin, who are unable to discontinue treatment for 24 hours prior to bladder injection and staged InterStim® procedure.
Serum creatinine level greater than twice the upper limit of normal within the previous year prior to enrollment.
Surgical treatment for stress incontinence (sling, Burch or urethral injection) or pelvic organ prolapse recommended or planned at enrollment by study investigator(s).
Prior stress incontinence or prolapsed surgery within the last 6 months prior to enrollment.
Allergy to lidocaine or bupivacaine.
Prior pelvic radiation.
Uninvestigated hematuria.
Greater than or equal to Stage III vaginal prolapse.
Known allergy to Botox A®.
Use of a vaginal pessary.

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Cindy Amundsen, MD	Duke University	Study Chair
Holly Richter, PhD, MD	University of Alabama at Birmingham	Principal Investigator
Shawn A. Menefee, MD	Kaiser Permanente, San Diego, CA	Principal Investigator
Sandip Vasada, MD	The Cleveland Clinic	Principal Investigator
Deborah L. Myers, MD	Brown/Women and Infants Hospital of Rhode Island	Principal Investigator
Yoko Kumesu, MD	University of New Mexico	Principal Investigator
Lily Arya, MD	University of Pennsylvania	Principal Investigator
Jerry Lowder, MD	University of Pittsburgh	Principal Investigator
W. Thomas Gregory, MD	Oregon Health and Science University	Principal Investigator
Dennis Wallace, PhD

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham, Department of Obstetrics and Gynecology		Birmingham	Alabama	35249-7333	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33620895	Derived	Hendrickson WK, Amundsen CL, Rahn DD, Meyer I, Bradley MS, Smith AL, Myers DL, Jelovsek JE, Lukacz ES. Comparison of 100 U With 200 U of Intradetrusor OnabotulinumToxinA for Nonneurogenic Urgency Incontinence. Female Pelvic Med Reconstr Surg. 2021 Mar 1;27(3):140-146. doi: 10.1097/SPV.0000000000001020.
31895722	Derived	Richter HE, Jelovsek JE, Iyer P, Rogers RG, Meyer I, Newman DK, Bradley MS, Harm-Ernandes I, Dyer KY, Wohlrab K, Mazloomdoost D, Gantz MG; Eunice Kennedy Shriver NICHD Pelvic Floor Disorders Network and the National Institutes of Health Office of Research on Women's Health. Characteristics Associated With Clinically Important Treatment Responses in Women Undergoing Nonsurgical Therapy for Fecal Incontinence. Am J Gastroenterol. 2020 Jan;115(1):115-127. doi: 10.14309/ajg.0000000000000482.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed. InterStim® device: Eligible subjects will complete baseline assessments, be randomized and scheduled for first stage lead placement (FSLP) InterStim®. The criterion for an initial clinical response to InterStim® therapy will be d

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

All eligible participants who provided at least 1 post-baseline diary assessment.

Arm/Group Information

ID	Title	Description
BG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
BG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00063.1± 11.8 BG00162.9± 11.5 BG00263.0± 11.6

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Age <65 years

Title	Measurements
	BG00091 BG001100 BG002

Sex/Gender, Customized

Count of Participants

Participants

Title

Denominators

Categories

Female

Title	Measurements
	BG000174 BG001190 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00010 BG00118 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG000149 BG001154 BG002

Menopausal Status

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Pre-menopausal	BG00018 BG00120 BG002

History of Recurrent UTIs

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
No history of recurrent UTIs	BG000149 BG001166 BG002

Urinary Incontinence Episodes Per Day

Mean

Standard Deviation

Episodes per day

Title

Denominators

Categories

Total incontinence episodes per day

Title	Measurements
	BG0005.8± 3.0 BG0016.0± 3.0 BG002

Nocturia (number of night voids per day)

Mean

Standard Deviation

Voids per day

Title

Denominators

Categories

Title	Measurements
	BG0001.7± 1.4 BG0011.7± 1.2 BG002

Overactive Bladder Questionnaire - Short Form (OABq-SF)

Values range from 0 to 100 with higher scores on the symptom scale indicating greater severity of symptoms and higher scores on the quality of life scale indicating better quality of life.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

OABq-SF Symptom Bother

Title	Measurements
	BG00076.1± 16.8 BG001

Urinary Frequency and Nocturia - Sandvik Questionnaire

Patient-reported measure of incontinence severity as assessed on a scale of slight (1-2) to very severe (10-12) using the standard scoring algorithm.

Count of Participants

Participants

Title

Denominators

Categories

Slight

Title	Measurements
	BG0001 BG001

Urinary Distress Inventory Short Form (UDI-SF)

Values range from 0 to 100 with higher scores indicating greater distress.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG00059.2± 16.9 BG00160.9± 18.3

Incontinence Impact Questionnaire Short Form (IIQ-SF)

Values range from 0 to 100 with higher scores indicating worse quality of life.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG00052.5± 25.8 BG00152.7± 27.6

Health Utilities Index Mark 3 (HUI-3)

Values are defined such that the score for dead is 0; the score for perfect health is 1.0.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG0000.74± 0.28 BG0010.71± 0.30

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Urge Urinary Incontinence (UUI) Episodes

The primary outcome is the change from baseline in mean number of UUI episodes over the first 6-month visit period (1, 2, 3, 4, 5 and 6 month assessments); and is measured using 3-day bladder diaries administered monthly for the first 6 month visit period.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Mean

95% Confidence Interval

UUI episodes

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.

Units	Counts
Participants	OG000174 OG001190

Title

Denominators

Categories

Title	Measurements
	OG000-3.25(-3.64 to -2.87) OG001-3.89(-4.26 to -3.52)

Secondary

Number of Participants With Improvement of Bladder Function and Urinary Leakage

Proportion of subjects who report adequate improvement of their bladder function and urinary leakage with the Patient Global Impression of Improvement Questionnaire (PGI-I) at 6 months. Adequate improvement is defined as a rating of 1, 2, or 3 (better) on the patient-reported measure of perceived improvement with treatment on a scale of 1 (very much better) to 7 (very much worse).

All eligible participants who provided at least 1 postbaseline diary assessment.

Posted

Count of Participants

Participants

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection

Secondary

Change in Overactive Bladder

Change in mean Overactive Bladder Questionnaire Short Form (OABq-SF) score throughout baseline to the first 6-month visit (1, 2, 3, 4, 5, and 6-month assessments). Values range from 0 to 100 with higher scores on the symptom scale indicating greater severity of symptoms and higher scores on the quality of life scale indicating a better quality of life.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Mean

95% Confidence Interval

units on a scale

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection

Secondary

Urinary Frequency and Nocturia

Change in mean number of urinary incontinence episodes (any type) and nocturia episodes from baseline over the first 6-month visit period (1, 2, 3, 4, 5, and 6-month assessments) as measured by the 3 day bladder diary.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Mean

95% Confidence Interval

Number of episodes

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.

Secondary

Severity of Urge Incontinence Symptoms

Severity of urge incontinence symptoms at 6 month visit period as measured by the Sandvik questionnaire. The Sandvik score is a patient-reported measure of incontinence severity as assessed on a scale of slight (1-2), moderate (3-6), severe (8-9), very severe (12) to severe (10-12) using a standard scoring algorithm.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Count of Participants

Participants

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.

Secondary

Treatment Satisfaction (OAB-SATq Treatment Satisfaction, Adverse Effects, Treatment Endorsement, and Convenience)

Treatment satisfaction as measured by the mean Overactive Bladder Satisfaction of Treatment Questionnaire (OAB-SATq) score at 6 months (6 month assessment). The OAB-SATq score ranges from 0 to 100 and includes 5 subscales: treatment satisfaction, side effects, treatment endorsement, convenience, and treatment preference, with higher scores reflecting better satisfaction.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Mean

95% Confidence Interval

units on a scale

6 months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection

Secondary

Treatment Satisfaction (OAB-SATq Treatment Preference)

Treatment preference as measured by the Overactive Bladder Satisfaction of Treatment Questionnaire (OAB-SATq) at 6 months (6 month assessment).OAB-SATq treatment preference is a binary outcome that is classified as yes if a participant answers either "Slight preference for the treatment I am receiving now" or "Definitely prefer the treatment I am receiving now" to the question "Do you prefer the treatment that you received since entering this study to the treatment you received before the study?"

All eligible participants who provided at least 1 postbaseline diary assessment.

Posted

Count of Participants

Participants

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001

Secondary

Quality of Life (UDI-SF)

Change from baseline in quality of life measures over the first 6 month visit period (6 month assessment) as measured by the change in mean Urinary Distress Inventory Short Form (UDI-SF) score. The UDI-SF scale has a range from 0 to 100 with higher scores indicating greater distress.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Mean

95% Confidence Interval

units on a scale

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.

Secondary

Quality of Life (IIQ-SF)

Change from baseline in quality of life measures over the first 6 month visit period (6 month assessment) as measured by the change in the mean Incontinence Impact Questionnaire short form (IIQ-SF) score. The IIQ-SF scale has a range from 0 to 100 with higher scores indicating a worse quality of life.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Mean

95% Confidence Interval

units on a scale

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.

Secondary

Quality of Life (HUI-3)

Change from baseline in quality of life measures over the first 6 month visit period (6 month assessment) as measured by the Health Utility Index, Version 3 (HUI-3). The HUI 3 scale has a range from 0 to 1 with higher scores representing better health.

All eligible participants who provided at least 1 post-baseline diary assessment.

Posted

Mean

95% Confidence Interval

units on a scale

6 Months

ID	Title	Description
OG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
OG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	InterStim® Device	The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 1st stage is lead placement into the S3 foramen with best response to stimulation.The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.			58	178	20	178
EG001	Botox® Injection	Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.			58	191	66	191

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0011 events1 affected191 at risk
Bronchitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0003 events3 affected178 at risk EG0011 events1 affected191 at risk
Clostridium difficile infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0004 events2 affected178 at risk EG0010 events0 affected191 at risk
Clostridium difficile sepsis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Device related infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Diverticulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Epiglottitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Incision site infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Infectious colitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Influenza	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0012 events2 affected191 at risk
Lymphangitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Meningitis viral	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Osteomyelitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Parotitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Pneumonia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0003 events3 affected178 at risk EG0010 events0 affected191 at risk
Post procedural infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Pyelonephritis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Sepsis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0014 events4 affected191 at risk
Subcutaneous abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Urinary tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Wound infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0012 events1 affected191 at risk
Wound infection staphylococcal	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Abdominal hernia repair	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Anal sphincterotomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Appendicectomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Cardiac operation	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Endotracheal intubation	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Gastrectomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0011 events1 affected191 at risk
Gastric bypass	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Hernia hiatus repair	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Hysterectomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0011 events1 affected191 at risk
Intestinal resection	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Knee arthroplasty	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0012 events2 affected191 at risk
Knee operation	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Mammoplasty	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Medical device change	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0002 events2 affected178 at risk EG0010 events0 affected191 at risk
Medical device removal	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0003 events3 affected178 at risk EG0010 events0 affected191 at risk
Skin graft	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Spinal laminectomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Tenotomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Thyroidectomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Anastomotic ulcer	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0011 events1 affected191 at risk
Carotid artery restenosis	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0012 events2 affected191 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0012 events2 affected191 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Incision site pain	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Seroma	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Tongue injury	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0013 events3 affected191 at risk
Cauda equina syndrome	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Dementia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Dizziness	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0012 events2 affected191 at risk
Intracranial aneurysm	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Loss of consciousness	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Radiculopathy	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Seizure	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0002 events2 affected178 at risk EG0011 events1 affected191 at risk
Syncope	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0012 events2 affected191 at risk
Toxic encephalopathy	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0002 events2 affected178 at risk EG0011 events1 affected191 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Angina pectoris	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0005 events3 affected178 at risk EG0013 events2 affected191 at risk
Bradycardia	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Cardiac arrest	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Coronary artery disease	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0012 events2 affected191 at risk
Myocardial infarction	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Pericardial effusion	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0012 events1 affected191 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0005 events4 affected178 at risk EG0013 events3 affected191 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Abdominal hernia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Ileus	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Inflammatory bowel disease	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Intestinal cyst	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Oesophageal mass	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Salivary gland calculus	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Chest pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0002 events2 affected178 at risk EG0012 events2 affected191 at risk
Device deployment issue	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Device dislocation	General disorders	MedDRA (17.0)	Systematic Assessment	EG0003 events3 affected178 at risk EG0010 events0 affected191 at risk
Hernia	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0011 events1 affected191 at risk
Medical device site pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0014 events4 affected191 at risk
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Endometrial adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0011 events1 affected191 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Obliterative bronchiolitis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Agitation	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Confusional state	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Depression	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Depression suicidal	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Mental status changes	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Obesity	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Renal failure	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Urinary retention	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Hypertrophic cardiomyopathy	Congenital, familial and genetic disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected191 at risk
Cyst aspiration	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Sexual abuse	Social circumstances	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk
Lymphoedema	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected178 at risk EG0010 events0 affected191 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Urinary Tract Infection	Infections and infestations	MedDRA (17.0)			EG00028 events20 affected178 at risk EG001107 events66 affected191 at risk

ID	Term
D053202	Urinary Incontinence, Urge

Ancestor Terms

ID	Term
D014549	Urinary Incontinence
D014555	Urination Disorders
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D059411	Lower Urinary Tract Symptoms
D020924	Urological Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D019274	Botulinum Toxins, Type A

Ancestor Terms

ID	Term
D001905	Botulinum Toxins
D008666	Metalloendopeptidases
D010450	Endopeptidases
D010447	Peptide Hydrolases
D006867	Hydrolases
D004798	Enzymes
D045762	Enzymes and Coenzymes
D045726	Metalloproteases
D001426	Bacterial Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D001427	Bacterial Toxins
D014118	Toxins, Biological
D001685	Biological Factors

Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.