Clinical trial NCT04754737: Antibiotic Usage Prior to OnabotulinumtoxinA Injection
Official title: Optimizing Antibiotic Use in Treatment of Overactive Bladder: Evaluating the Need for Prophylactic Antibiotics Prior to OnabotulinumtoxinA Injection in Patients Without Urinary Tract Infection
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Antibiotic Stewardship
Overactive Bladder
Onabotulinumtoxin A
UTI
Lead sponsor: Benaroya Research Institute
Sponsor class: OTHER
Collaborators: name: Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction
name: Stony Brook University
name: Northwell Health
name: Virginia Mason Hospital/Medical Center
First posted: 2021-02-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, un-blinded
Primary purpose: PREVENTION

Brief summary: Intradetrusor injection of onabotulinumtoxinA, which is performed through a cystoscopic procedure, has been demonstrated to be efficacious in the treatment of both neurogenic and non-neurogenic overactive bladder (OAB), and is FDA approved as a treatment for overactive bladder. Intradetrusor of onabotulinumtoxinA is currently standard of care of patients with OAB who have persistent OAB symptoms despite behavioral therapies and oral medication treatments for OAB. As one of the main adverse events associated with intradetrusor injection of onabotulinumtoxinA is UTI, and published guidelines for cystoscopic procedures with manipulation recommend the use of prophylactic antibiotics, a single dose of prophylactic antibiotic is administered prior to this procedure. However, these recommendations are primarily based on data from randomized controlled trials (RCTs) involving antimicrobial prophylaxis during transurethral resection of the prostate. A previously published prospective study demonstrated that the rate of post-procedural UTI did not differ amongst patients with neurogenic bladder who did not receive prophylactic antibiotics and were asymptomatic for UTI, regardless of whether they had sterile urine cultures or asymptomatic bacteriuria, suggesting that patients who are not symptomatic for UTI may not require antibiotic prophylaxis prior to intradetrusor onabotulinumtoxinA injection. Studies have reported that up to 50% of antibiotic usage is inappropriate, leading to unnecessary exposure of patients to potential complications of antibiotic therapy, including Clostridium difficile infection which can cause recurrent diarrhea that may progress to sepsis and death, increasing antibiotic resistances, as well as dermal/allergic and gastro-intestinal manifestations. Therefore, in an effort to optimize antibiotic use, the investigators propose a prospective, randomized study to formally evaluate the differences in UTI frequency in subjects who have a negative urinalysis and are not symptomatic for UTI and receive prophylactic antibiotics at the time of intradetrusor onabotulinumtoxinA injection compared to those who do not receive prophylactic antibiotics at the time of injection. The proposed study seeks to evaluate the current practice standard of antibiotic prophylaxis prior to intradetrusor onabotulinumtoxin injection.

Detailed description: Intradetrusor injection of onabotulinumtoxinA, which is performed thorough a cystoscopic procedure, has been demonstrated to be efficacious in the treatment of both neurogenic and non-neurogenic overactive bladder (OAB), and is FDA approved as a treatment for OAB. Intradetrusor of onabotulinumtoxinA is currently standard of care in patients with persistent OAB symptoms despite behavioral therapies and oral medication treatments for OAB. As one of the main adverse events associated with intradetrusor injection of onabotulinumtoxinA is UTI, and published guidelines for cystoscopic procedures with manipulation recommend the use of prophylactic antibiotics, a single dose of prophylactic antibiotic is administered prior to this procedure as the current standard of care. However, the guideline recommendations are primarily based on data from randomized controlled trials (RCTs) involving antimicrobial prophylaxis during transurethral resection of the prostate, and does not address cystoscopic injection procedures like onabotulinumtoxinA injection. Studies have reported that up to 50% of antibiotic usage is inappropriate, leading to unnecessary exposure of patients to potential complications of antibiotic therapy, including Clostridium difficile infection which can cause recurrent diarrhea that may progress to sepsis and death, increasing antibiotic resistances, as well as dermal/allergic and gastro-intestinal manifestations. In an effort to optimize antibiotic usage, antimicrobial stewardship is required in nursing facilities, acute-care and critical care hospitals, as well as ambulatory care centers. These efforts highlight the importance of re-evaluating our current practice standard of prophylactic antibiotic administration in urologic procedures. A prospective study that included patients undergoing intradetrusor onabutulinumtoxin injections who were not symptomatic for UTI and did not receive antibiotic prophylaxis demonstrated that the rate of post-procedure UTI within 6 weeks of treatment was not significantly different in those with a sterile urine culture compared to those with asymptomatic bacteriuria, suggesting that in patients who are not symptomatic for UTI, antibiotic prophylaxis may not be necessary prior to intradetrusor onabotulinumtoxin injection. To date, there have been no randomized studies that evaluate differences in outcomes when prophylactic antibiotics are not given prior to onabotulinumtoxinA injection. Therefore, in an effort to optimize antibiotic use, the investigators propose a prospective, randomized study to formally investigate whether there is a difference in the rate of symptomatic post-procedure UTI after intradetrusor onabotulinumtoxin when antibiotic prophylaxis is given compared to when antibiotic prophylaxis is not given in patients who are not symptomatic for UTI and have a negative urinalysis. The proposed study seeks to evaluate the current practice standard of antibiotic prophylaxis prior to intradetrusor onabotulinumtoxin injection.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18
* Diagnosis of OAB who have failed 1st and 2nd line therapies per the AUA/SUFU OAB guidelines (including bladder training, dietary modification and pharmacotherapy with an anticholinergic and/or beta-3 agonist)
* Not symptomatic for UTI at the time of injection
* Negative urinalysis at the time of the injection defined as: negative for nitrites and leukocyte esterace, with urine white blood cell count less than 5 per high-power field
* Consent to participate in the study.

Exclusion Criteria:

* Antibiotic usage within 48 hours prior to intradetrusor onabotulinumtoxinA injection
* Women who are pregnant or planning to become pregnant, women who are breastfeeding
* Concurrent use of onabotulinumtoxinA injection with maximum cumulative dose exceeding 400 units in a 3-month interval.

Primary outcomes:
measure: symptomatic UTI
timeFrame: 14 days
Secondary outcomes:
measure: Percentage of subjective improvement in overactive bladder symptoms
timeFrame: 14-30 days
measure: Rate of adverse events including dysuria, gross hematuria, and urinary retention
timeFrame: 14-30 days
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: Stony Brook Medicine
state: New York
Study officials:
affiliation: Stony Brook Medicine
name: Justina Tam, MD
role: PRINCIPAL_INVESTIGATOR
References: