Prophylactic Antibiotics for Bladder Cancer

Overseen By Judith Graziano

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Must not be taking: Antimicrobials

Disqualifiers: Poor renal function, Allergy, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate postoperative period

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether skipping preventive antibiotics after bladder cancer surgery results in the same or fewer infections compared to taking them. Specifically, it compares outcomes for patients who do not receive antibiotics to those who take nitrofurantoin after surgery. The trial aims to assist patients with muscle-invasive bladder cancer planning to have their bladder surgically removed, particularly if they are not on other antibiotics or have allergies to them. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering patients a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently receiving antimicrobials for an active infection, you would not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nitrofurantoin, the antibiotic used in this study, is commonly prescribed for urinary tract infections. However, its long-term effects remain debated. For instance, one study found no increase in tumors in rats that took nitrofurantoin for two years. Conversely, some research suggests a possible link between nitrofurantoin and certain types of cancer in humans, though these findings are not conclusive.

Generally, nitrofurantoin is well-tolerated for short-term use, which is typical for treating infections. Most people do not experience serious side effects. However, discussing any concerns with a healthcare provider is important, especially if other health conditions exist or long-term use is considered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using nitrofurantoin for bladder cancer patients because it offers a proactive approach to preventing infections after surgery. Unlike the standard practice of administering antibiotics only when an infection is detected, this treatment aims to ward off infections before they start. Nitrofurantoin is known for its effectiveness against urinary tract infections, making it a promising candidate for reducing postoperative complications in bladder cancer patients. By potentially minimizing the risk of infection, this approach could lead to faster recovery times and improved overall outcomes for patients.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that taking preventive antibiotics, such as nitrofurantoin, after bladder cancer surgery can reduce the risk of urinary tract infections (UTIs) within 90 days. Studies have found that these antibiotics decrease infection-related problems post-surgery. Nitrofurantoin is as effective as other antibiotics in preventing repeat UTIs in adults. Some research also suggests that antibiotics might stop cancer cells from spreading, potentially lowering the chances of cancer recurrence. In this trial, participants in the treatment group will receive prophylactic antibiotics postoperatively, while the control group will not receive them unless needed for an infection. This evidence supports the idea that nitrofurantoin could help manage infections after bladder cancer surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Hamed Ahmadi, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for individuals with muscle invasive bladder cancer who are undergoing radical cystectomy and urinary diversion. Specific eligibility details aren't provided, but typically participants must meet certain health criteria to join.

Inclusion Criteria

I have bladder cancer and will have surgery to remove my bladder.

Exclusion Criteria

Pregnancy

Unable to provide Informed consent

I am currently on medication for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo radical cystectomy with urinary diversion and are randomized to receive either no prophylactic antibiotics or prophylactic oral antibiotic, nitrofurantoin, postoperatively

Immediate postoperative period

Follow-up

Participants are monitored for postoperative urinary tract infections and other outcomes

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Nitrofurantoin

Trial Overview The study compares the effect of not using prophylactic antibiotics to taking a specific antibiotic (nitrofurantoin) after surgery, by looking at urinary tract infection rates within 90 days post-operation.

How Is the Trial Designed?

Group I: Treatment group Experimental Treatment 1 Intervention

Prophylactic antibiotics postoperatively.

Group II: Control group Active Control 1 Intervention

No prophylactic antibiotics post operatively. Participants will receive antibiotics only if needed post-operatively such as for infection

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

In a study of 10,055 male patients with uncomplicated urinary tract infections (UTIs), nitrofurantoin was prescribed in 56% of cases, but it had a high treatment failure rate of 25%, especially among older patients.

Other antibiotics like ciprofloxacin and amoxicillin/clavulanic acid showed lower failure rates (10% and 20%, respectively), suggesting that nitrofurantoin may not be the best first-choice treatment for all males with uncomplicated UTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrofurantoin failure in males with an uncomplicated urinary tract infection: a primary care observational cohort study. Platteel, TN., Beets, MT., Teeuwissen, HA., et al.[2023]

Long-term use of nitrofurantoin, a common treatment for urinary tract infections, may lead to severe pulmonary complications, as demonstrated in a case of a 51-year-old woman who developed lung fibrosis after years of treatment.

The autopsy findings indicated that the lung fibrosis was likely induced by nitrofurantoin, highlighting the need for regular monitoring of patients on this medication for potential adverse pulmonary effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrofurantoin-induced pulmonary fibrosis: a case report. Goemaere, NN., Grijm, K., van Hal, PT., et al.[2021]

The study identified that a nitrofurantoin suspension with glycerin (0.2%) and sodium citrate (0.3%) significantly improved physical stability, making it a promising formulation for treating urinary tract infections.

The optimal formulation, which included Veegum (1%), sodium carboxyl methyl cellulose (1%), glycerin, sodium citrate, and sorbitol (20%), exhibited pseudoplastic behavior, indicating good flow properties and ease of use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of flocculating agents and structural vehicles on the physical stability and rheological behavior of nitrofurantoin suspension. Moghimipour, E., Salimi, A., Rezaee, S., et al.[2022]

In a study involving 65 hospitalized patients with acute urinary tract infections, treatment with a nitrofurantoin/sulphadiazine compound showed therapeutic effectiveness, highlighting its potential as a reliable antibacterial option.

The study emphasized the importance of monitoring for iatrogenic infections, as these patients were already severely ill, indicating a need for careful management to minimize additional risks during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of acute urinary tract infection with a nitrofurantoin-sulphadiazine compound preparation (author's transl)]. Griendl, W.[2013]

Nitrofurantoin remains an effective treatment for uncomplicated urinary tract infections (UTIs), particularly against common pathogens like E. coli, despite its long history of use and potential side effects.

Recent studies indicate that short-term nitrofurantoin therapy is well-tolerated and effective, making it a recommended first-line treatment in current guidelines, although it is contraindicated in late pregnancy and for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nitrofurantoin--clinical relevance in uncomplicated urinary tract infections]. Stock, I.[2014]

In a study of 13 dogs receiving nightly nitrofurantoin for recurrent urinary tract infections, the treatment was well tolerated and resulted in a median infection-free interval of 268 days, with eight dogs showing no positive urine cultures during therapy.

However, treatment failures were noted, particularly due to infections with nitrofurantoin-resistant Proteus spp., highlighting the need for monitoring and potential adjustments in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nightly nitrofurantoin as prophylaxis in dogs with recurrent urinary tract infections: 13 cases (2015-2021). Murray, O., Furrow, E., Granick, J., et al.[2023]

Long-term use of furantoin, a medication often used for urinary tract infections, can lead to serious side effects such as pulmonary fibrosis, as seen in this case following bladder tumor surgery.

The patient experienced acute respiratory failure and despite initial treatment success, she relapsed and ultimately succumbed to the complications, highlighting the risks associated with prolonged furantoin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pulmonary fibrosis secondary to nitrofurantoin]. Pérez Herms, S., Castellanos Acosta, R., Guzmán Fernández, A., et al.[2013]

A case study highlights that chronic use of nitrofurantoin can lead to pulmonary fibrosis, particularly in a patient who had undergone surgery for a bladder tumor.

Despite initial treatment success for respiratory issues, the patient experienced a relapse and ultimately died from complications related to the underlying disease, emphasizing the serious risks associated with long-term nitrofurantoin use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pulmonary fibrosis secondary to nitrofurantoin]. Pérez Herms, S., Castellanos Acosta, R., Guzmán Fernández, A., et al.[2013]

In a study involving 52 elderly patients with uncomplicated lower urinary tract infections, cinoxacin demonstrated a better antibacterial spectrum compared to nitrofurantoin, although both effectively cleared infections.

Cinoxacin was well-tolerated with no reported side effects, while 15% of patients on nitrofurantoin experienced significant side effects like anorexia and nausea, leading to some needing to stop treatment early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative drug study of lower urinary tract infections in elderly patients. Lindan, R.[2019]

Nitrofurantoin is a broad-spectrum antibiotic effective against both Gram-negative and Gram-positive bacteria, making it a valuable option for treating acute lower urinary tract infections, especially in the context of rising antibiotic resistance.

Recent data suggest that nitrofurantoin is particularly useful for managing urinary tract infections caused by multidrug-resistant pathogens, highlighting its importance as a treatment option when other oral antibiotics are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Old Antibiotics in the Era of Antibiotic Resistance. Highlighted Nitrofurantoin for the Treatment of Lower Urinary Tract Infections. Munoz-Davila, MJ.[2020]

Citations

1. auajournals.org auajournals.org/doi/pdf/10.1097/JU.0000000000004586

Do Prophylactic Antibiotics Decrease the Rate of Urinary ... Conclusions: Prophylactic antibiotics for 30 days after RARC were associated with lower 90-day UTIs, infectious complications, UTI-related ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40279497/

Do Prophylactic Antibiotics Decrease the Rate of Urinary ... Conclusions: Prophylactic antibiotics for 30 days after RARC were associated with lower 90-day UTIs, infectious complications, UTI-related ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090429503011786

Antitumor activity of common antibiotics against superficial ... The administration of antibiotics after transurethral resection of bladder tumors might prevent seeding of cancer cells and thereby decrease the recurrence rate ...

4. evidence.nihr.ac.uk evidence.nihr.ac.uk/alert/nitrofurantoin-is-as-effective-as-other-long-term-antibiotics-for-preventing-recurrent-urinary-tract-infections/

Nitrofurantoin is as effective as other long-term antibiotics ... The analysis of 12 trials found no difference in successful cure of urinary tract infections in adult women with recurrent urinary tract ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3202002/

Guidelines for the diagnosis and management of recurrent ... Continuous low-dose antibiotic prophylaxis is effective at preventing UTIs. A 2008 Cochrane Database systematic review pooled 10 trials enrolling 430 women in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6388119/

Risk of Cancer after Lower Urinary Tract Infection However, a significant increase was observed in the incidence of bladder cancer in men after antibiotic treatment for more than 7 days (Table 6) ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/0300483X9090056M

Evaluation of nitrofurantoin on the two stages of urinary ... No increase in tumor incidence was observed in rats fed nitrofurantoin at a level of 0.18% of the diet for 2 years compared to a control group. Also, no ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK526248/

Nitrofurantoin - Pharmaceutical Drugs - NCBI Bookshelf - NIH In a hypothesis-generating cohort study, use of nitrofurantoin was associated with the occurrence of cancers of the female genital tract and nervous system, but ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0887233321000977

The numerical probability of carcinogenicity to humans ... For nitrofurantoin, a 99.9% probability of carcinogenicity to humans was reckoned. Therefore, a risk-benefit evaluation on the in-force authorization of ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/020064Orig1s029lbl.pdf

Macrobid® (Nitrofurantoin Capsules, USP) (monohydrate ... Based on urinary pharmacokinetic data, the extent and rate of urinary excretion of nitrofurantoin from ... Safety and effectiveness in pediatric patients ...