Antibiotic Prophylaxis for UTIs in Overactive Bladder

Overseen By Jordan Gisseman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Walter Reed National Military Medical Center

Must be taking: Nitrofurantoin

Must not be taking: Antibiotics

Disqualifiers: Neurogenic bladder, Recurrent UTI, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal use of antibiotics to prevent urinary tract infections (UTIs) in individuals with overactive bladder (OAB) receiving intradetrusor onabotulinumtoxinA injections. The researchers aim to determine whether a three-day course of the antibiotic nitrofurantoin is more effective than a single dose in preventing UTIs. Women with OAB or interstitial cystitis/bladder pain syndrome (IC/BPS) planning to receive onabotulinumtoxinA injections at Walter Reed National Military Medical Center may be suitable candidates for this trial. Participants will be randomly assigned to receive either the three-day course or a single dose during their injection. The trial seeks to identify the best method to prevent UTIs while minimizing unnecessary antibiotic use. As a Phase 4 trial, this research focuses on understanding how the already FDA-approved treatment can benefit more patients.

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 participate if you are already taking antibiotics at the time of the procedure.

What is the safety track record for nitrofurantoin?

Research has shown that nitrofurantoin is generally safe for preventing urinary tract infections (UTIs). Studies indicate that serious side effects occur in only 0.02 to 1.5 out of every 1,000 users, meaning most people tolerate it well. Nitrofurantoin effectively reduces the risk of UTIs compared to not taking preventive medicine. Although antibiotics can cause side effects, the risk of serious issues with nitrofurantoin remains low. Its current use for UTI prevention suggests it is safe for this purpose. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore more efficient methods for preventing UTIs in individuals with overactive bladder through the use of nitrofurantoin. Unlike the standard of care, which typically involves longer courses of antibiotics, these treatments focus on shorter regimens. The "3 day arm" offers a brief, three-day course of nitrofurantoin, while the "single dose arm" tests a one-time dose. These approaches could potentially reduce antibiotic exposure and resistance, making them promising options for safer, more convenient UTI prevention.

What evidence suggests that this trial's treatments could be effective for preventing UTIs in overactive bladder?

Research has shown that nitrofurantoin effectively prevents urinary tract infections (UTIs) caused by common bacteria like E. coli and E. faecalis. Studies have identified nitrofurantoin as a good preventive option for individuals who frequently experience UTIs, particularly those caused by specific bacteria. In past cases, the rate of UTIs was 11.4% when using nitrofurantoin. This trial will compare two dosing regimens of nitrofurantoin: a 3-day course and a single dose, both administered at the time of intradetrusor injection of onabotulinumtoxinA for overactive bladder. Nitrofurantoin is often chosen because it reduces the risk of UTIs without causing resistance to multiple antibiotics, making it a reliable choice for preventing UTIs after procedures like bladder injections. ^{1 5 6 7 8}

Who Is on the Research Team?

Jordan Gisseman, MD

Principal Investigator

Walter Reed National Military Medical Center

Are You a Good Fit for This Trial?

This trial is for female patients aged 18 or older who visit the urogynecology and urology clinics at Walter Reed National Military Medical Center, have been diagnosed with overactive bladder (OAB) or interstitial cystitis/bladder pain syndrome (IC/BPS), and opt for Botox injections into the bladder. Participants must not currently have a UTI.

Inclusion Criteria

I have been diagnosed with overactive bladder or interstitial cystitis.

I can follow instructions and attend all follow-up appointments.

I am planning to get Botox injections for my overactive bladder or interstitial cystitis.

Exclusion Criteria

Post void residual bladder volume ≥150mL

I have a condition where my bladder doesn't function properly due to nerve damage.

I am not allergic to, pregnant, or have had over 400 units of Botox in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person or phone)

Treatment

Participants receive intradetrusor onabotulinumtoxinA injections with either a single dose or a 3-day course of nitrofurantoin

1 day

1 visit (in-person)

Follow-up

Participants are monitored for UTI symptoms, diagnoses, and secondary outcomes

30-45 days

Follow-up by phone, email, or message

What Are the Treatments Tested in This Trial?

Interventions

• Nitrofurantoin

Trial Overview The study aims to find out if taking one dose of Nitrofurantoin 100mg at the time of Botox injection into the bladder is as effective in preventing UTIs as taking it twice daily for three days starting from the procedure day. It's a non-blinded randomized controlled trial comparing these two antibiotic regimens.

How Is the Trial Designed?

Group I: Single dose arm Experimental Treatment 1 Intervention

Subjects will be given a single dose of 100mg nitrofurantoin by mouth at the time of intradetrusor injection of 100u onabotulinumtoxinA

Group II: 3 day arm Active Control 1 Intervention

Subjects will be given a 3 day twice daily course of 100mg nitrofurantoin by mouth starting at the time of intradetrusor injection of 100u onabotulinumtoxinA

Nitrofurantoin is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Macrobid for:

• Urinary tract infections
• Prostatitis

Approved in Canada as Macrodantin for:

• Urinary tract infections
• Prostatitis

Approved in European Union as Furadantin for:

• Urinary tract infections
• Prostatitis

Who Is Running the Clinical Trial?

Walter Reed National Military Medical Center

Lead Sponsor

Trials

149

Recruited

33,800+

Published Research Related to This Trial

Nitrofurantoin is effective for treating urinary tract infections (UTIs) in male veterans, with a suggested minimum creatinine clearance (CrCl) of 60 ml/min needed to achieve an 80% cure rate, especially for Gram-negative infections.

The effectiveness of nitrofurantoin varies based on the type of bacteria causing the UTI, with Gram-negative infections showing better outcomes at lower CrCl levels compared to Gram-positive infections, while adverse effects remained consistent regardless of renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of nitrofurantoin in outpatient male veterans. Ingalsbe, ML., Wojciechowski, AL., Smith, KA., et al.[2020]

Imidafenacin, administered at doses of 0.1-0.2 mg before sleeping, significantly reduced nighttime frequency of urination in patients with overactive bladder (OAB) suffering from nocturia, demonstrating its efficacy over an 8-week period.

The treatment was found to be safe, with no increase in postvoid residual volume and no serious adverse events reported, indicating a favorable safety profile for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Imidafenacin before Sleeping on Nocturia. Kadekawa, K., Onaga, T., Shimabukuro, S., et al.[2015]

Imidafenacin 0.1 mg taken twice daily significantly reduced the number of daily micturitions and urge incontinence episodes in Taiwanese patients with overactive bladder after 12 weeks of treatment, compared to placebo.

The study, involving 118 patients, showed that while adverse events occurred in both groups, the safety profile of imidafenacin was acceptable, with common side effects including dry mouth and constipation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled, parallel study to evaluate the efficacy and safety of imidafenacin in patients with overactive bladder in Taiwan. Chuang, YC., Lin, CC., Chow, PM., et al.[2021]

In a study of 173 women with recurrent urinary tract infections (UTIs), StroVac vaccination showed a success rate of 79.3% in preventing UTIs after two years, compared to 59.2% for Nitrofurantoin, indicating that StroVac provides longer-lasting protection.

StroVac had a significantly lower discontinuation rate due to side effects (2.3%) compared to Nitrofurantoin (18.4%), suggesting it is a safer alternative for UTI prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vaccination with StroVac for recurrent urinary tract infections in women: a comparative single-centre study. Nestler, S., Grüne, B., Schilchegger, L., et al.[2022]

In a study involving 449 patients undergoing pelvic organ prolapse and urinary incontinence surgery, antibiotic prophylaxis with nitrofurantoin significantly reduced the rate of positive urine cultures and symptomatic urinary tract infections (UTIs) compared to a placebo.

Specifically, the use of nitrofurantoin led to a decrease in positive urine cultures (46% vs 61%) and symptomatic UTIs at the time of catheter removal (7.2% vs 19.8%), demonstrating its efficacy in preventing infections immediately following surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled comparison of the effect of nitrofurantoin monohydrate macrocrystals on the development of urinary tract infections after surgery for pelvic organ prolapse and/or stress urinary incontinence with suprapubic catheterization. Rogers, RG., Kammerer-Doak, D., Olsen, A., et al.[2022]

A study involving 142 women assessed the effectiveness of nitrofurantoin in preventing bacteriuria after urodynamics and cystourethroscopy, but found no significant difference in infection rates between those receiving nitrofurantoin and those receiving a placebo.

The overall rate of bacteriuria post-procedure was 6%, with 7% in the nitrofurantoin group and 5% in the placebo group, indicating that a short course of nitrofurantoin did not effectively reduce the risk of infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of antibiotic prophylaxis for combined urodynamics and cystourethroscopy. Cundiff, GW., McLennan, MT., Bent, AE.[2022]

In a study of 163 patients with benign prostatic hyperplasia and persistent overactive bladder symptoms, the combination of tamsulosin, dutasteride, and imidafenacin significantly improved symptoms compared to tamsulosin and dutasteride alone, with a mean difference in symptom score of -1.18 by week 24.

The combination therapy not only enhanced overactive bladder symptoms but also improved quality of life without serious adverse effects, suggesting it is a safe and effective treatment option for patients not responding to tamsulosin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of combination therapy with tamsulosin, dutasteride and imidafenacin for the management of overactive bladder symptoms associated with benign prostatic hyperplasia: A multicenter, randomized, open-label, controlled trial (DIrecT Study). Yamanishi, T., Asakura, H., Seki, N., et al.[2019]

In a study involving 401 Japanese patients with overactive bladder, imidafenacin significantly reduced incontinence episodes and urinary urgency compared to placebo, demonstrating a clear dose-dependent efficacy.

The 0.1 mg dose of imidafenacin was found to be well tolerated with minimal side effects, making it the recommended dose for further large-scale studies, while higher doses showed increased incidence of dry mouth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled phase II dose-finding study of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder. Homma, Y., Yamaguchi, T., Yamaguchi, O.[2012]

In a study of over 29,000 women, nitrofurantoin was found to be equally effective in treating urinary tract infections (UTIs) in those with moderate renal impairment compared to those without, showing no increased risk of treatment ineffectiveness.

However, women with more severe renal impairment (less than 50 ml/min) had a significantly higher risk of serious pulmonary adverse events leading to hospitalization when treated with nitrofurantoin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care. Geerts, AF., Eppenga, WL., Heerdink, R., et al.[2021]

Imidafenacin significantly improves symptoms of overactive bladder (OAB) and reduces nocturia, as shown in a multicenter study with patients assessed at baseline, 4 weeks, and 8 weeks using various scoring methods.

The drug enhances sleep quality, particularly in older patients (75 years and above), by increasing bladder capacity and decreasing nighttime urine volume, making it an effective and safe treatment option for nocturia associated with OAB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of imidafenacin on nocturia and sleep disorder in patients with overactive bladder. Wada, N., Watanabe, M., Kita, M., et al.[2015]

Nitrofurantoin is effective in preventing urinary tract infections (UTIs), showing a significant reduction in risk compared to no prophylaxis, with a risk ratio of 0.38 based on a systematic review of 26 controlled trials involving 3052 patients.

While nitrofurantoin is generally safe, it is associated with a higher risk of non-severe adverse effects compared to other antibacterials, although severe adverse effects are rare, occurring in only 0.02-1.5 per 1000 users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrofurantoin's efficacy and safety as prophylaxis for urinary tract infections: a systematic review of the literature and meta-analysis of controlled trials. Muller, AE., Verhaegh, EM., Harbarth, S., et al.[2022]

In a study of 446 patients treated with nitrofurantoin for acute cystitis, the overall clinical cure rate was 86.5%, showing that nitrofurantoin is effective regardless of gender or renal function, as no significant differences were found.

Adverse events were rare, occurring in only 2% of patients, indicating that nitrofurantoin is a safe option for treating cystitis in both males and females, even those with varying degrees of renal dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Review on the Safety and Efficacy of Nitrofurantoin for the Treatment of Cystitis in the Veteran Population With or Without Renal Insufficiency. Welch, E., Sheth, S., Ashong, CN., et al.[2022]

In a study of 42,298 patients aged 65 and older, alternative antibiotics like cefalexin, ciprofloxacin, and co-amoxiclav were associated with lower odds of treatment failure compared to nitrofurantoin, suggesting they may be better options for older patients with UTIs.

However, prescribing cefalexin or ciprofloxacin was linked to higher odds of hospitalization for sepsis and increased mortality, indicating that while alternative antibiotics may reduce treatment failure, they could pose additional risks for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choice of Empirical Antibiotic Therapy and Adverse Outcomes in Older Adults With Suspected Urinary Tract Infection: Cohort Study. Ahmed, H., Farewell, D., Francis, NA., et al.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557479/

Recurrent Urinary Tract Infections - StatPearls - NCBI Bookshelf [78] Long-term, low-dose antibiotic prophylaxis is effective but requires high patient compliance and risks resistance. Patients may relapse when prophylaxis is ...

2. withpower.com withpower.com/trial/phase-4-overactive-bladder-syndrome-oabs-3-2024-3f651

Antibiotic Prophylaxis for UTIs in Overactive Bladder The effectiveness of nitrofurantoin varies based on the type of bacteria causing the UTI, with Gram-negative infections showing better outcomes at lower CrCl ...

3. mdpi.com mdpi.com/2079-6382/14/10/998

Antimicrobial Prophylaxis for Recurrent Urinary Tract ... Conclusions: Our findings strongly suggest that nitrofurantoin is an effective prophylactic choice for rUTIs caused by common uropathogens (E. coli, E. faecalis ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06387329?locStr=United%20States&country=United%20States&cond=Interstitial%20Cystitis%2FPainful%20Bladder%20Syndrome&aggFilters=ages:child%20adult%20older,funderType:nih%20fed,status:rec&rank=5

NCT06387329 | Bladder Botox UTI Antibiotic Prophylaxis The primary outcome was UTI within 30 days by culture, or by empiric treatment with improvement in symptoms. The overall UTI rate was 11.4%.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6718139/

Long-term prescribing of nitrofurantoin for urinary tract ... Long-term prescription of nitrofurantoin may reduce UTIs in veterans with SCI and there is no evidence that it promotes multi-drug resistance.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27542332/

Nitrofurantoin's efficacy and safety as prophylaxis for ... Cohort studies reported severe adverse effect frequencies of 0.02-1.5 per 1000 nitrofurantoin users. Conclusions: Nitrofurantoin is effective in the prevention ...

7. academic.oup.com academic.oup.com/jac/article-pdf/42/3/363/9838068/420363.pdf

Efficacy and safety profile of long-term nitrofurantoin in ... Our results show that prophylaxis should continue for 12 months, as this gives a better result than a shorter period. 8,10,11,32 Most patients had a reduced ...

8. auanet.org auanet.org/guidelines-and-quality/guidelines/recurrent-uti

Recurrent Uncomplicated Urinary Tract Infections in Women Preliminary data suggests that continuous prophylaxis with low-dose antibiotics leads to lower rates of antibiotic resistance and fewer adverse events than ...