Antibiotic Usage for Overactive Bladder

Recruiting at 1 trial location

Overseen By Justina Tam, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Benaroya Research Institute

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

200 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use antibiotics within 48 hours before the procedure.

What data supports the effectiveness of the drug onabotulinumtoxinA for treating overactive bladder?

Research shows that onabotulinumtoxinA (Botox) injections are effective in treating symptoms of overactive bladder, including those that occur after certain surgeries. However, there is a risk of urinary tract infections and urinary retention, which are complications that need to be managed. ^{1 2 3 4 5}

Is onabotulinumtoxinA (Botox) safe for treating overactive bladder?

OnabotulinumtoxinA (Botox) is generally considered safe for treating overactive bladder, but it can increase the risk of urinary tract infections and urinary retention (difficulty emptying the bladder). ^{1 2 4 6 7}

How is the drug onabotulinumtoxinA (Botox) used for overactive bladder different from other treatments?

OnabotulinumtoxinA (Botox) is unique for overactive bladder treatment because it is injected directly into the bladder muscle, helping to relax it and reduce symptoms, unlike oral medications that work systemically. This localized approach can be beneficial for patients who do not respond well to standard oral treatments. ^{1 8 9 10 11}

Research Team

Justina Tam, MD

Principal Investigator

Stony Brook Medicine

Eligibility Criteria

Adults over 18 with an overactive bladder (OAB) who haven't improved with first and second-line treatments can join. They must not show symptoms or test positive for a urinary tract infection (UTI) at the time of treatment. Pregnant or breastfeeding women, recent antibiotic users, and those treated with high doses of onabotulinumtoxinA are excluded.

Inclusion Criteria

Age ≥ 18

You do not have symptoms of a urinary tract infection when you receive the injection.

Your urine test should not show signs of infection, and the number of white blood cells should be low.

Exclusion Criteria

Women who are pregnant or planning to become pregnant, women who are breastfeeding

You have taken antibiotics in the 48 hours before getting an injection of onabotulinumtoxinA into the bladder.

You have received more than 400 units of onabotulinumtoxinA injections within a 3-month period.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intradetrusor injection of onabotulinumtoxinA with or without prophylactic antibiotics

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the rate of symptomatic UTIs and adverse events

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• cystoscopic injection of onabotulinumtoxinA
• No antibiotic
• Prophylactic antibiotic

Trial Overview The study is testing if giving antibiotics before injecting onabotulinumtoxinA into the bladder helps prevent UTIs in OAB patients without current infections. Participants will either receive a prophylactic antibiotic or no antibiotic before the procedure, to see which approach is better.

Participant Groups

Group I: Prophylactic antibiotic Experimental Treatment 2 Interventions

These patients will receive the current standard of care, which is to receive a single dose of prophylactic antibiotics just prior to receiving intravesical injection of Onabotulinumtoxin A via cystoscopy. The specific prophylactic antibiotics will vary depending on patient's prior urine culture sensitivities and patient medication allergies/sensitivities and medical comorbidities.

Group II: No antibiotics Experimental Treatment 2 Interventions

These patients will receive no prophylactic antibiotics prior to receiving intravesical injection of Onabotulinumtoxin A via cystoscopy.

cystoscopic injection of onabotulinumtoxinA is already approved in United States, European Union for the following indications:

Approved in United States as Botox for:

• Overactive bladder
• Urinary incontinence
• Neurogenic detrusor overactivity
• Chronic migraine
• Spasticity
• Cervical dystonia
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus

Approved in European Union as Botox for:

• Overactive bladder
• Urinary incontinence
• Neurogenic detrusor overactivity
• Chronic migraine
• Spasticity
• Cervical dystonia
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus

Who Is Running the Clinical Trial?

Benaroya Research Institute

Lead Sponsor

Trials

50

Recruited

12,300+

Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction

Collaborator

Trials

7

Recruited

360+

Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU)

Collaborator

Trials

1

Recruited

200+

Stony Brook University

Collaborator

Trials

225

Recruited

41,700+

Northwell Health

Collaborator

Trials

481

Recruited

470,000+

Virginia Mason Hospital/Medical Center

Collaborator

Trials

23

Recruited

8,500+

Findings from Research

In a study of 284 patients receiving intravesical Botox® for detrusor overactivity, those who took a 3-day course of oral fluoroquinolone antibiotics had a significantly lower rate of urinary tract infections (UTIs) at 20.8% compared to 36% in those who received a single intramuscular dose of ceftriaxone.

The findings suggest that a longer course of antibiotics, especially for patients with a positive preprocedure urine culture, may further reduce the risk of postprocedure UTIs following Botox® injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the ideal antibiotic prophylaxis for intravesically administered Botox injection? A comparison of two different regimens. Houman, J., Moradzadeh, A., Patel, DN., et al.[2020]

In a study involving 62 patients with overactive bladder, a single instillation of liposomal botulinum toxin significantly reduced micturition events and urinary urgency compared to a placebo, indicating its efficacy in managing symptoms.

Importantly, this treatment did not increase the risk of urinary retention, suggesting it may be a safer alternative to traditional botulinum toxin injections for patients with refractory overactive bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder instillation of liposome encapsulated onabotulinumtoxina improves overactive bladder symptoms: a prospective, multicenter, double-blind, randomized trial. Chuang, YC., Kaufmann, JH., Chancellor, DD., et al.[2022]

In a study of 208 women with idiopathic overactive bladder (OAB) treated with 100 U of Botox, older and multiparous women were found to be at a higher risk for urinary retention, particularly those requiring clean intermittent self-catheterization (CISC).

The risk of urinary retention significantly decreased by 2 weeks post-injection, indicating that close monitoring during this period is crucial for OAB patients after receiving Botox treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary retention in female OAB after intravesical Botox injection: who is really at risk? Miotla, P., Cartwright, R., Skorupska, K., et al.[2018]

In a study of 174 patients receiving a single intravesical injection of 100U onabotulinumtoxinA for idiopathic detrusor overactivity, 79.3% reported successful outcomes at 3 months, indicating the treatment's efficacy.

Despite common adverse events like acute urinary retention and large postvoid residual, these did not negatively impact the long-term therapeutic success rates, suggesting that the treatment remains effective even in the presence of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Difficult Urination Does Not Affect the Successful Outcome after 100U OnabotulinumtoxinA Intravesical Injection in Patients with Idiopathic Detrusor Overactivity. Chen, YC., Kuo, HC.[2015]

In a study of 102 women, both those with idiopathic overactive bladder (OAB) and those with de novo OAB after midurethral sling surgery showed significant improvement in symptoms after receiving onabotulinumtoxinA injections, with similar rates of being completely dry (41.5% vs. 38.8%).

The treatment led to a notable reduction in daily voids and incontinence episodes for both groups, with urinary retention occurring in only four patients, indicating that the safety profile of onabotulinumtoxinA is acceptable even in women who have undergone previous surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of botulinum toxin injection in the treatment of de novo OAB symptoms following midurethral sling surgery. Miotla, P., Futyma, K., Cartwright, R., et al.[2018]

In a study of 281 women undergoing onabotulinumtoxinA injections for urgency incontinence, using multiple doses of prophylactic antibiotics did not significantly reduce the rate of urinary tract infections compared to a single dose, with infection rates of 13.8% and 10.3% respectively.

The study found that having a positive urine culture within 30 days post-injection greatly increased the odds of developing a urinary tract infection, highlighting the importance of monitoring urine cultures in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary tract infection following intradetrusor onabotulinumtoxina injection for non-neurogenic urgency incontinence: single- vs. multi-dose prophylactic antibiotic treatment regimens. Crouss, T., Kim, Y., Lai, E., et al.[2023]

Botulinum toxin-A significantly improves symptoms of idiopathic overactive bladder (OAB), including reduced urinary frequency and incontinence episodes, based on a review of 12 randomized controlled trials involving 1,020 participants.

While effective, botulinum toxin-A is associated with a higher risk of urinary retention and urinary tract infections compared to placebo, suggesting that lower doses may provide a better balance of benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin-A injections for idiopathic overactive bladder: a systematic review and meta-analysis. Cui, Y., Wang, L., Liu, L., et al.[2022]

In a study of 565 women undergoing Botox treatment for overactive bladder, 92.9% received some form of antibiotic prophylaxis, yet this did not significantly reduce the incidence of urinary tract infections (UTIs) post-procedure, with a UTI rate of 30.4%.

No specific route of antibiotic administration (IV, oral, or combination) was found to be more effective than no prophylaxis at preventing UTIs, suggesting that current prophylactic practices may need reevaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic regimen and route of administration do not alter rates of urinary tract infection after intravesical botulinum toxin injection for overactive bladder. Eckhardt, SE., Takashima, Y., Handler, SJ., et al.[2022]

A systematic review of 27 studies involving 2,100 patients indicated that prophylactic antibiotics are beneficial in reducing urinary tract infections (UTIs) after onabotulinum toxin type A (BTX) injections for overactive bladder syndrome, particularly in patients with idiopathic OAB.

The analysis suggests that continuing antibiotics for 2-3 days post-injection may help prevent UTIs, although no specific antibiotic regimen was identified as optimal due to the variability in the data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis for onabotulinum toxin A injections: systematic review and meta-analysis. Getaneh, FW., Simhal, R., Sholklapper, T., et al.[2023]

In a study of 616 procedures involving intravesical botulinum toxin A (BoNTA) injections for detrusor overactivity in patients with spinal cord injury, only 1.8% developed symptomatic urinary tract infections (UTIs), suggesting that the procedure is relatively safe.

The findings indicate that a single dose of antibiotics prior to the BoNTA injection is sufficient to prevent UTIs, challenging the need for prolonged antibiotic prophylaxis, although further randomized clinical trials are needed for confirmation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of different antibiotic protocols for asymptomatic bacteriuria in patients with neurogenic bladder treated with botulinum toxin A. Paradella, AC., Musegante, AF., Brites, C.[2022]

In a study of 216 patients receiving onabotulinumtoxin A (BTX-A) for overactive bladder, only 8.3% of patients in the operating room received antibiotics that matched the American Urological Association's 2008 guidelines, compared to 82% in the office setting, indicating significant variability in antibiotic practices.

The rates of urinary tract infections (UTIs) within 30 days post-BTX-A injection did not significantly differ based on whether the antibiotics used were concordant with the guidelines, suggesting that adherence to these antibiotic recommendations may not impact UTI rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic use, best practice statement adherence, and UTI rate for intradetrusor onabotulinumtoxin-A injection for overactive bladder: A multi-institutional collaboration from the SUFU Research Network (SURN). Shapiro, K., Anger, J., Cameron, AP., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

What is the ideal antibiotic prophylaxis for intravesically administered Botox injection? A comparison of two different regimens. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Bladder instillation of liposome encapsulated onabotulinumtoxina improves overactive bladder symptoms: a prospective, multicenter, double-blind, randomized trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Urinary retention in female OAB after intravesical Botox injection: who is really at risk? [2018]

4. Australia pubmed.ncbi.nlm.nih.gov

Difficult Urination Does Not Affect the Successful Outcome after 100U OnabotulinumtoxinA Intravesical Injection in Patients with Idiopathic Detrusor Overactivity. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of botulinum toxin injection in the treatment of de novo OAB symptoms following midurethral sling surgery. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Urinary tract infection following intradetrusor onabotulinumtoxina injection for non-neurogenic urgency incontinence: single- vs. multi-dose prophylactic antibiotic treatment regimens. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Botulinum toxin-A injections for idiopathic overactive bladder: a systematic review and meta-analysis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Antibiotic regimen and route of administration do not alter rates of urinary tract infection after intravesical botulinum toxin injection for overactive bladder. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis for onabotulinum toxin A injections: systematic review and meta-analysis. [2023]

10. Brazil pubmed.ncbi.nlm.nih.gov

Comparison of different antibiotic protocols for asymptomatic bacteriuria in patients with neurogenic bladder treated with botulinum toxin A. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Antibiotic use, best practice statement adherence, and UTI rate for intradetrusor onabotulinumtoxin-A injection for overactive bladder: A multi-institutional collaboration from the SUFU Research Network (SURN). [2023]