Overactive Bladder, Overactive Bladder Syndrome, Urinary Bladder, Overactive, Urinary Frequency/Urgency, Urinary Incontinence, Urinary Urgency
Conditions
Keywords
OnabotulinumtoxinA, Bladder Injections
Brief summary
Patients with overactive bladder (OAB) will be randomly assigned (like a flip of a coin) to receive 100 units of onabotulinumtoxinA injected into the bladder at either 3 sites or 10 sites. Patient satisfaction and the effectiveness of the medication will be evaluated.
Detailed description
Overactive bladder (OAB) is a common condition which often has a negative impact on health related quality of life. Primary and secondary treatments include behavior modification, pelvic floor physical therapy, and OAB medications. OnabotulinumtoxinA (BTX) is a well-established third line therapy for refractory OAB. BTX has transitioned over the years from a procedure conducted in the operating room to one that is commonly done in the clinic or physician office. While ten injection sites is commonly practiced, there has been continuing interest in reducing the number of injection sites to make the technique more tolerable and more efficient. In this study, refractory OAB patients will be randomized to receive 100 units of BTX over 3 or 10 injection sites. The investigators hypothesize that decreasing the number of injection sites may improve patient tolerability and satisfaction with this office-based procedure and potentially reduce the rates of adverse events including hematuria and urinary tract infection.
Interventions
DRUGOnabotulinumtoxinA 100Unit Injection
Initial treatment with the option of repeat injections every 3 months
Sponsors
Corewell Health East
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
2 arm parallel study with 1 to 1 randomization
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women and men, 18 years of age or older * Self-reported failed conservative care of behavioral modifications and/or oral medications for the treatment of OAB * Average urinary frequency of \> 8 voids per day as recorded on initial 3-day voiding diary * Self-reported bladder symptoms \> 3 months * Discontinued antimuscarinics/beta-3 agonists for \> 2 weeks prior to study enrollment. May restart antimuscarinics/beta-3 agonists if indicated \> 6 weeks after Botox injections. * Capable of giving informed consent * Capable and willing to follow all study-related procedures * Previous OnabotulinumtoxinA injection at least three months prior to study enrollment.
Exclusion criteria
* Pregnant or planning to become pregnant during study duration * Diagnosis of neurogenic bladder with the exception of highly functioning stroke patients * If a patient has had a previous neuromodulation device placed, it will have to be turned off for 2 weeks for a washout period and remain off throughout the study * Previous non-responders to onabotulinumtoxinA (BTX) therapy * Patient cannot be receiving percutaneous nerve stimulation (PTNS) therapy. If patient is receiving PTNS, they need to stop for 1 month prior to entering the study. * Refusal to self-catheterize or have indwelling catheter in the event of urinary retention * Use of investigational drug/device therapy within past 4 weeks * Participation in any clinical investigation involving or impacting gynecologic, urinary or renal function within past 4 weeks * Current or past history of any physical condition that, in the investigator's opinion, might put the subject at risk or interfere with study results interpretation * Pelvic radiation treatment * Known hypersensitivity to OnabotulinumtoxinA. * Previous infection at OnabotulinumtoxinA injection site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Incontinence Episodes Per Day | 3 months after the initial injection | Participants will be asked to complete a 3-day voiding diary. On the diary participants will record the number of occurrences of voids over a 24 hour period for 3 consecutive days. Number of voids at 3 months are recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Urine Leakage | 3 months after the initial injection | Per the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). This validated questionnaire provides a measure to assess the impact of symptoms of incontinence on quality of life and outcome of treatment. Question items include frequency of urinary incontinence, amount of leakage, overall impact of urinary incontinence, and a self-diagnostic item. Scoring is between 0-21 with greater values indicating increased severity. |
| Change in Overactive Bladder Symptoms | 3 months after the initial injection | Per the Global Response Assessment (GRA). Participants will assess overall how their OAB symptoms/condition changed since starting the study. Participants will select, Markedly worse (1), Moderately worse (2), Mildly worse (3), Same (unchanged) (4), Slightly improved (5), Moderately improved (6), or Markedly improved (7). Scores are from 1-7 with a greater score indicating a greater improvement of symptoms. Numbers of participants reporting each assessment will be reported. |
| Degree of Bladder Symptom Bother | 3 months after the initial injection | Per the Overactive Bladder Questionnaire-Short Form (OABq-SF). This validated measure evaluates overactive bladder symptom severity and health related quality of life. For each question, participants will answer how bothered they are by their urinary symptoms from not at all (1), a little bit (2), somewhat (3), quite a bit (4), a great deal (5), and a very great deal (5). Each question will be scored. Scores range from 19-114. The higher the score the greater perceived degree of bladder symptom bother. |
| Overall Voiding Symptoms at 3 Months | 3 months after the initial injection | Per the 3-day voiding diary. Participants will be asked to complete a 3-day voiding diary. On the diary participants will record the number of occurrences of voids, urge and stress incontinence episodes over a 24 hour period for 3 consecutive days. |
| Safety of Bladder Injections | At study completion, 3 months after the initial injection | Frequency and severity of study-related adverse events |
| Overall Patient Pain Tolerability With Treatment | After the initial injection | Per the Visual Analog Scale (VAS). Participants will record the amount of pain of performing the treatment on a Visual Analog Scale from 0 (no pain) to 10 (worst pain imaginable). Visual analog scores will be gathered at the end of the injection visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3 Injection Sites OnabotulinumtoxinA 100Unit injection into 3 sites throughout the bladder
OnabotulinumtoxinA 100Unit Injection: Initial treatment with the option of repeat injections every 3 months | 1 |
| 10 Injection Sites OnabotulinumtoxinA 100Unit injection into 10 sites throughout the bladder
OnabotulinumtoxinA 100Unit Injection: Initial treatment with the option of repeat injections every 3 months | 5 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Increase Botox dose | 0 | 1 |
| Overall Study | Lower dose due to elevated post void residual (PVR) | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | 3 Injection Sites | 10 Injection Sites | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 3 Participants | 3 Participants |
| Baseline number of stress incontinence episodes | 0 Stress incontinence episodes STANDARD_DEVIATION 0 | 0.2 Stress incontinence episodes STANDARD_DEVIATION 0.4 | 0.17 Stress incontinence episodes STANDARD_DEVIATION 0.4 |
| Baseline number of urge incontinence episodes | 21 Urge incontinence episodes STANDARD_DEVIATION 0 | 20.6 Urge incontinence episodes STANDARD_DEVIATION 12.1 | 20.7 Urge incontinence episodes STANDARD_DEVIATION 10.8 |
| Baseline number of voids | 14 Voids STANDARD_DEVIATION 0 | 14.9 Voids STANDARD_DEVIATION 6.02 | 14.8 Voids STANDARD_DEVIATION 5.4 |
| Baseline severity of urine leakage | 16 score on a scale STANDARD_DEVIATION 0 | 15 score on a scale STANDARD_DEVIATION 8.5 | 15.2 score on a scale STANDARD_DEVIATION 7.6 |
| Baseline Symptom Bother | 64 score on a scale STANDARD_DEVIATION 0 | 87.4 score on a scale STANDARD_DEVIATION 14.7 | 83.5 score on a scale STANDARD_DEVIATION 16.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United States | 1 participants | 5 participants | 6 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 5 |
| other Total, other adverse events | 1 / 1 | 0 / 5 |
| serious Total, serious adverse events | 0 / 1 | 0 / 5 |
Outcome results
Primary
Number of Incontinence Episodes Per Day
Participants will be asked to complete a 3-day voiding diary. On the diary participants will record the number of occurrences of voids over a 24 hour period for 3 consecutive days. Number of voids at 3 months are recorded.
Time frame: 3 months after the initial injection
Population: Due to the small number of participants statistical analysis was limited. 3 participants completed 3 month diary data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 Injection Sites | Number of Incontinence Episodes Per Day | 0 Incontinency episodes | Standard Deviation 0 |
| 10 Injection Sites | Number of Incontinence Episodes Per Day | 15.5 Incontinency episodes | Standard Deviation 21.9 |
Secondary
Change in Overactive Bladder Symptoms
Per the Global Response Assessment (GRA). Participants will assess overall how their OAB symptoms/condition changed since starting the study. Participants will select, Markedly worse (1), Moderately worse (2), Mildly worse (3), Same (unchanged) (4), Slightly improved (5), Moderately improved (6), or Markedly improved (7). Scores are from 1-7 with a greater score indicating a greater improvement of symptoms. Numbers of participants reporting each assessment will be reported.
Time frame: 3 months after the initial injection
Population: Due to a small number of participants data analysis was limited. 3 participants completed GRA data at 3 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 3 Injection Sites | Change in Overactive Bladder Symptoms | Slightly Improved | 0 Participants |
| 3 Injection Sites | Change in Overactive Bladder Symptoms | Slightly Worse | 0 Participants |
| 3 Injection Sites | Change in Overactive Bladder Symptoms | Moderately Improved | 0 Participants |
| 3 Injection Sites | Change in Overactive Bladder Symptoms | Moderately Worse | 0 Participants |
| 3 Injection Sites | Change in Overactive Bladder Symptoms | No change | 0 Participants |
| 3 Injection Sites | Change in Overactive Bladder Symptoms | Markedly Worse | 0 Participants |
| 3 Injection Sites | Change in Overactive Bladder Symptoms | Markedly Improved | 1 Participants |
| 10 Injection Sites | Change in Overactive Bladder Symptoms | Markedly Worse | 0 Participants |
| 10 Injection Sites | Change in Overactive Bladder Symptoms | Markedly Improved | 0 Participants |
| 10 Injection Sites | Change in Overactive Bladder Symptoms | Moderately Improved | 0 Participants |
| 10 Injection Sites | Change in Overactive Bladder Symptoms | Slightly Improved | 1 Participants |
| 10 Injection Sites | Change in Overactive Bladder Symptoms | No change | 0 Participants |
| 10 Injection Sites | Change in Overactive Bladder Symptoms | Slightly Worse | 1 Participants |
| 10 Injection Sites | Change in Overactive Bladder Symptoms | Moderately Worse | 0 Participants |
Secondary
Degree of Bladder Symptom Bother
Per the Overactive Bladder Questionnaire-Short Form (OABq-SF). This validated measure evaluates overactive bladder symptom severity and health related quality of life. For each question, participants will answer how bothered they are by their urinary symptoms from not at all (1), a little bit (2), somewhat (3), quite a bit (4), a great deal (5), and a very great deal (5). Each question will be scored. Scores range from 19-114. The higher the score the greater perceived degree of bladder symptom bother.
Time frame: 3 months after the initial injection
Population: Due to the small number of participants data analysis was limited. 3 participants completed data at 3 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 Injection Sites | Degree of Bladder Symptom Bother | 23 score on scale | Standard Error 0 |
| 10 Injection Sites | Degree of Bladder Symptom Bother | 43 score on scale | Standard Error 26.9 |
Secondary
Overall Patient Pain Tolerability With Treatment
Per the Visual Analog Scale (VAS). Participants will record the amount of pain of performing the treatment on a Visual Analog Scale from 0 (no pain) to 10 (worst pain imaginable). Visual analog scores will be gathered at the end of the injection visit.
Time frame: After the initial injection
Population: 6 subjects completed baseline VAS scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 Injection Sites | Overall Patient Pain Tolerability With Treatment | 2 score on a scale | Standard Deviation 0 |
| 10 Injection Sites | Overall Patient Pain Tolerability With Treatment | 3 score on a scale | Standard Deviation 1.1 |
Secondary
Overall Voiding Symptoms at 3 Months
Per the 3-day voiding diary. Participants will be asked to complete a 3-day voiding diary. On the diary participants will record the number of occurrences of voids, urge and stress incontinence episodes over a 24 hour period for 3 consecutive days.
Time frame: 3 months after the initial injection
Population: Due to small number of participants data analysis was limited. 3 subjects had data available for 3 month timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3 Injection Sites | Overall Voiding Symptoms at 3 Months | Average number of voids | 12.6 Episodes | Standard Error 0 |
| 3 Injection Sites | Overall Voiding Symptoms at 3 Months | Urge incontinence episodes | 0 Episodes | Standard Error 0 |
| 3 Injection Sites | Overall Voiding Symptoms at 3 Months | Stress incontinence episodes | 0 Episodes | Standard Error 0 |
| 10 Injection Sites | Overall Voiding Symptoms at 3 Months | Average number of voids | 13.2 Episodes | Standard Error 2.6 |
| 10 Injection Sites | Overall Voiding Symptoms at 3 Months | Urge incontinence episodes | 11 Episodes | Standard Error 15.6 |
| 10 Injection Sites | Overall Voiding Symptoms at 3 Months | Stress incontinence episodes | 1.5 Episodes | Standard Error 2.1 |
Secondary
Safety of Bladder Injections
Frequency and severity of study-related adverse events
Time frame: At study completion, 3 months after the initial injection
Population: 3 participants completed the study through the 3 month visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 3 Injection Sites | Safety of Bladder Injections | Post-void residual over 300 ml, severity mild | 1 Participants |
| 3 Injection Sites | Safety of Bladder Injections | Urinary tract infection, severity mild | 1 Participants |
| 10 Injection Sites | Safety of Bladder Injections | Post-void residual over 300 ml, severity mild | 0 Participants |
| 10 Injection Sites | Safety of Bladder Injections | Urinary tract infection, severity mild | 0 Participants |
Secondary
Severity of Urine Leakage
Per the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). This validated questionnaire provides a measure to assess the impact of symptoms of incontinence on quality of life and outcome of treatment. Question items include frequency of urinary incontinence, amount of leakage, overall impact of urinary incontinence, and a self-diagnostic item. Scoring is between 0-21 with greater values indicating increased severity.
Time frame: 3 months after the initial injection
Population: Due to small number of participants data analysis was limited. 3 participants had data at 3 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 Injection Sites | Severity of Urine Leakage | 3 score on a scale | Standard Deviation 0 |
| 10 Injection Sites | Severity of Urine Leakage | 7.5 score on a scale | Standard Deviation 7.5 |