Prophylactic Antibiotic Administration for Bladder OnabotulinumtoxinA Injection

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

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.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder; Urge Incontinence; Urinary Incontinence, Urge; Overactive Bladder Syndrome
• Intervention / Treatment: Drug: Single-Dose Antibiotic; Drug: Multi-Dose Antibiotic

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 Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibiotic Adverse Events	Summarize rates of adverse events related to antibiotics in each group.	4 weeks
Symptomatic Urinary Retention	Estimate the rate of symptomatic urinary retention requiring catheterization among refractory overactive bladder patients who experience a UTI.	4 weeks

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Emily Slopnick, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Actual): June 8, 2023
• Study Completion (Actual): June 8, 2023

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: overactive bladder; incontinence; urge incontinence
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Urinary Incontinence; Urinary Incontinence, Urge; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 22-698

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No