Overactive Bladder, Overactive Bladder Syndrome, Urge Incontinence, Urinary Incontinence, Urge
Conditions
Keywords
incontinence, overactive bladder, urge incontinence
Brief summary
The goal of this clinical trial is to evaluate the outcomes of differing durations of antibiotic prophylaxis with bladder onabotulinumtoxinA injection in patients with refractory overactive bladder. The main question it aims to answer are: • Is the incidence of post-procedure UTI similar between single-dose and multi-day durations of peri-procedural antibiotics? Participants will be randomized to single-dose versus multi-day dose of antibiotic prophylaxis with bladder onabotulinumtoxinA injection. Researchers will compare incidence of UTI in each group to see if there is a significant difference.
Detailed description
* After informed consent is obtained, urinalysis will be collected. Post-void residual will also be assessed by bladder scan if not already documented in the electronic medical record in the prior three months. * Patients with positive urinalysis and symptomatic for UTI will be excluded from the study. * Patients will be randomized in a 1:1 ratio to one of two groups. * Group 1 will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection. * Group 2 will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection. * The same antibiotic will be continued for 3 days of total antibiotic administration with additional doses prescribed to the patient's pharmacy. * Bladder onabotulinumtoxinA injection and dosing will be completed based on the surgeon's standard technique and template. * Bladder onabotulinumtoxinA injection will be completed by staff or fellows in the Female Pelvic Medicine and Reconstructive Surgery division of the Genitourinary and Kidney Institute. * Patients will be followed for 4 weeks after the procedure. * At 4 weeks study investigators will contact the patient by phone to evaluate for any UTIs or adverse events not previously reported by the patient during the study period. * Chart review will occur at 4 weeks to assess for any unreported events. * Other than this additional phone call, post-operative patient management will not deviate from the standard of care. * Patients will be instructed to report symptomatic UTIs, urinary retention, or any other adverse events related to onabotulinumtoxinA or antibiotic to investigators. * Patients that report symptoms suggestive of a UTI will result in obtaining a urine culture. * Symptomatic, culture proven UTIs will be treated with appropriate antibiotics per the current AUA guidelines. * Symptoms suggestive of urinary retention, such as increased urinary frequency, voiding small amounts of urine, or feelings of incomplete bladder emptying, will result in obtaining a post void residual (PVR) and urinalysis. * Patients will undergo teaching to perform self, clean intermittent catheterization of the bladder per the discretion of the operating surgeon. * Any adverse reactions to the prescribed antibiotic will result in discontinuation of the antibiotic and managed according to the severity of the reaction. Antibiotic regimens: Allergy, prior urine culture resistance or another contraindication to first line antibiotic will result in the patient being prescribed second line antibiotic and so forth. First line: Group 1: trimethoprim / sulfamethoxazole 800/160 mg once pre-procedure Group 2: trimethoprim / sulfamethoxazole 800/160 mg once pre-procedure plus 800/160 mg every twelve hours for 6 total doses Second line: Group 1: cefalexin 500 mg once pre-procedure Group 2: cefalexin 500 mg once pre-procedure plus 500 mg every twelve hours for 6 total doses Third line: Group 1: nitrofurantoin 100 mg once pre-procedure Group 2: nitrofurantoin 100 mg once pre-procedure plus 100 mg every twelve hours for 6 total doses Fourth line: Group 1: ciprofloxacin 500 mg once pre-procedure Group 2: ciprofloxacin 500 mg once pre-procedure plus 500 mg every twelve hours for 6 total doses
Interventions
DRUGSingle-Dose Antibiotic
Allergy, prior urine culture resistance or another contraindication to first line antibiotic will result in the patient being prescribed second line antibiotic and so forth. First line: Arm 1: trimethoprim / sulfamethoxazole 800/160 mg once pre-procedure Second line: Arm 1: cefalexin 500 mg once pre-procedure Third line: Arm 1: nitrofurantoin 100 mg once pre-procedure Fourth line: Arm 1: ciprofloxacin 500 mg once pre-procedure
DRUGMulti-Dose Antibiotic
Allergy, prior urine culture resistance or another contraindication to first line antibiotic will result in the patient being prescribed second line antibiotic and so forth. First line: Arm 2: trimethoprim / sulfamethoxazole 800/160 mg once pre-procedure plus 800/160 mg every twelve hours for 6 total doses Second line: Arm 2: cefalexin 500 mg once pre-procedure plus 500 mg every twelve hours for 6 total doses Third line: Arm 2: nitrofurantoin 100 mg once pre-procedure plus 100 mg every twelve hours for 6 total doses Fourth line: Arm 2: ciprofloxacin 500 mg once pre-procedure plus 500 mg every twelve hours for 6 total doses
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Men and women 18 years of age or older with refractory overactive bladder or neurogenic bladder will be randomized in a 1:1 ratio into one of two groups until the targeted sample size is met: * The single dose group will receive one dose of antibiotic prior to intradetrusor Botox injection. * Individuals in the multi-dose group will receive one dose of antibiotic prior to intradetrusor Botox injection and additional antibiotics for a total of three days of antibiotic administration. Random permuted block randomization with block sizes of 2, 4, 6, and 8 will be used to assign eligible patients to treatment groups
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants with planned in-office bladder onabotulinumtoxinA injection * Men or Women Age ≥ 18 * Able to read, speak, and write in English * No contraindication to injection of onabotulinumtoxinA - hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation * Willingness and ability to initiate intermittent catheterization post-treatment if required * No contraindication to oral antibiotics * No active antibiotic therapy for any indication at the time of onabotulinumtoxinA injection * Have not participated in this study before
Exclusion criteria
* Any type of catheterization to empty the bladder * Unwillingness or inability to initiate intermittent catheterization post-treatment if required * Less than 3 months since last bladder onabotulinumtoxinA injection * Pregnant and/or breastfeeding * Active symptomatic UTI the day of the procedure - new or worsening frequency, urgency, dysuria, hematuria, suprapubic/flank pain, fevers or chills * History of recurrent UTI * Prior development of urinary retention or incomplete bladder emptying after bladder onabotulinumtoxinA injection requiring catheterization of any type
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Establish Noninferiority of the Single Dose Antibiotic Administration to the Multi-dose Antibiotic Administration. | 4 weeks | To assess this aim, the rate of postoperative urinary tract infection (UTI) within 4 weeks following bladder onabotulinumtoxinA injection will be compared between groups. Noninferiority will be declared if the incidence of UTI in the single dose group is not more than UTI incidence in the multiple dose group within statistical variability, by the prespecified noninferiority margin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibiotic Adverse Events | 4 weeks | Summarize rates of adverse events related to antibiotics in each group. |
| Symptomatic Urinary Retention | 4 weeks | Estimate the rate of symptomatic urinary retention requiring catheterization among refractory overactive bladder patients who experience a UTI. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1: Single-Dose Antibiotic Prophylaxis Patients will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection.
Single-Dose Antibiotic: Allergy, prior urine culture resistance or another contraindication to first line antibiotic will result in the patient being prescribed second line antibiotic and so forth.
First line:
Arm 1: trimethoprim / sulfamethoxazole 800/160 mg once pre-procedure
Second line:
Arm 1: cefalexin 500 mg once pre-procedure
Third line:
Arm 1: nitrofurantoin 100 mg once pre-procedure
Fourth line:
Arm 1: ciprofloxacin 500 mg once pre-procedure | 50 |
| 2: Multi-Dose Antibiotic Prophylaxis Patients will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection. The same antibiotic will be continued for 3 days of total antibiotic administration with additional doses prescribed to the patient's pharmacy.
Multi-Dose Antibiotic: Allergy, prior urine culture resistance or another contraindication to first line antibiotic will result in the patient being prescribed second line antibiotic and so forth.
First line:
Arm 2: trimethoprim / sulfamethoxazole 800/160 mg once pre-procedure plus 800/160 mg every twelve hours for 6 total doses
Second line:
Arm 2: cefalexin 500 mg once pre-procedure plus 500 mg every twelve hours for 6 total doses
Third line:
Arm 2: nitrofurantoin 100 mg once pre-procedure plus 100 mg every twelve hours for 6 total doses
Fourth line:
Arm 2: ciprofloxacin 500 mg once pre-procedure plus 500 mg every twelve hours for 6 total doses | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | 1: Single-Dose Antibiotic Prophylaxis | 2: Multi-Dose Antibiotic Prophylaxis | Total |
|---|---|---|---|
| Age, Continuous | 69.42 years | 64.62 years | 67.02 years |
| Body Mass Index (BMI) | 32.26 kg/m^2 | 34.14 kg/m^2 | 33.20 kg/m^2 |
| Current Anti-Cholinergic Use | 7 participants | 7 participants | 14 participants |
| Current Beta-3 Agonist Use | 6 participants | 7 participants | 13 participants |
| Current Posterior Tibial Nerve Stimulation (PTNS) Use | 0 participants | 0 participants | 0 participants |
| Current Sacral Neuromodulation Use | 4 participants | 4 participants | 8 participants |
| Current Tobacco Use | 6 participants | 4 participants | 10 participants |
| Current Vaginal Estrogen use | 4 participants | 8 participants | 12 participants |
| Diabetes Mellitus | 14 Participants | 13 Participants | 27 Participants |
| Neurogenic Bladder | 2 participants | 1 participants | 3 participants |
| Previous Bladder Botox | 39 participants | 38 participants | 77 participants |
| Prior Anti-Cholinergic Use | 41 participants | 41 participants | 82 participants |
| Prior Beta-3 Agonist Use | 24 participants | 22 participants | 46 participants |
| Prior Posterior Tibial Nerve Stimulation (PTNS) Use | 3 participants | 1 participants | 4 participants |
| Prior Sacral Neuromodulation Use | 4 participants | 5 participants | 9 participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 50 participants | 50 participants | 100 participants |
| Sex: Female, Male Female | 46 Participants | 50 Participants | 96 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 4 Participants |
| Sleep Apnea | 22 participants | 10 participants | 32 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 4 / 50 | 5 / 50 |
| serious Total, serious adverse events | 0 / 50 | 1 / 50 |
Outcome results
Primary
Establish Noninferiority of the Single Dose Antibiotic Administration to the Multi-dose Antibiotic Administration.
To assess this aim, the rate of postoperative urinary tract infection (UTI) within 4 weeks following bladder onabotulinumtoxinA injection will be compared between groups. Noninferiority will be declared if the incidence of UTI in the single dose group is not more than UTI incidence in the multiple dose group within statistical variability, by the prespecified noninferiority margin.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1: Single-Dose Antibiotic Prophylaxis | Establish Noninferiority of the Single Dose Antibiotic Administration to the Multi-dose Antibiotic Administration. | 1 Participants |
| 2: Multi-Dose Antibiotic Prophylaxis | Establish Noninferiority of the Single Dose Antibiotic Administration to the Multi-dose Antibiotic Administration. | 1 Participants |
Secondary
Antibiotic Adverse Events
Summarize rates of adverse events related to antibiotics in each group.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1: Single-Dose Antibiotic Prophylaxis | Antibiotic Adverse Events | 0 Participants |
| 2: Multi-Dose Antibiotic Prophylaxis | Antibiotic Adverse Events | 0 Participants |
Secondary
Symptomatic Urinary Retention
Estimate the rate of symptomatic urinary retention requiring catheterization among refractory overactive bladder patients who experience a UTI.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1: Single-Dose Antibiotic Prophylaxis | Symptomatic Urinary Retention | 0 Participants |
| 2: Multi-Dose Antibiotic Prophylaxis | Symptomatic Urinary Retention | 1 Participants |