Single-Dose Versus Multi-Dose Prophylactic Antibiotic Administration for Bladder OnabotulinumtoxinA Injection

Sponsor

The Cleveland Clinic (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05719285

Collaborator

(none)

100

Enrollment

Location

Arms

6.8

Anticipated Duration (Months)

14.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder Overactive Bladder Syndrome Urge Incontinence Urinary Incontinence, Urge	Drug: Single-Dose Antibiotic Drug: Multi-Dose Antibiotic	Phase 4

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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 groupsMen 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

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Single-Dose Prophylactic Antibiotic Regimen for Bladder OnabotulinumtoxinA Injection; A Prospective Non-Inferiority Trial

Actual Study Start Date :

Dec 6, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1: Single-Dose Antibiotic Prophylaxis Patients will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection.	Drug: 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 Other Names: ARM 1: Single-Dose Antibiotic Prophylaxis
Active Comparator: 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.	Drug: 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 Other Names: ARM 2: Multi-Dose Antibiotic Prophylaxis

Arm

Intervention/Treatment

Active Comparator: 1: Single-Dose Antibiotic Prophylaxis

Patients will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection.

Drug: Single-Dose Antibiotic

Other Names:

ARM 1: Single-Dose Antibiotic Prophylaxis

Active Comparator: 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.

Drug: 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

Other Names:

ARM 2: Multi-Dose Antibiotic Prophylaxis

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Rate of UTI [2 to 4 weeks]
Characterize the rate of postoperative UTI in the 2-to 4-week period following bladder onabotulinumtoxinA injection in each group.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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