Prophylactic Antibiotics for Bladder Cancer

Overseen By Maressa Twedt

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

Trial Summary

What is the purpose of this trial?

Using a randomized 2 arm design, this study is being conducted to test for non-inferiority of no prophylactic antibiotic therapy versus the prophylactic oral antibiotic, nitrofurantoin, through comparison of rates of postoperative urinary tract infections within the 90-day postoperative period in patients with muscle invasive bladder cancer who undergo radical cystectomy with urinary diversion.

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 nitrofurantoin safe for humans?

Nitrofurantoin has been used for a long time to treat urinary tract infections in adults, children, and pregnant women, but it can cause serious side effects like lung damage (pulmonary fibrosis), liver problems, and nerve damage. ^{1 2 3 4 5}

How does the drug nitrofurantoin differ from other treatments for bladder cancer?

Nitrofurantoin is unique because it is primarily used as an antibiotic for urinary tract infections, not typically for bladder cancer. Its use in this trial as a prophylactic (preventive) antibiotic for bladder cancer is novel, as it is not a standard treatment for this condition. ^{6 7 8 9 10}

Research Team

Hamed Ahmadi, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

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 am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

References

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

Safety and efficacy of nightly nitrofurantoin as prophylaxis in dogs with recurrent urinary tract infections: 13 cases (2015-2021). [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

[Pulmonary fibrosis secondary to nitrofurantoin]. [2013]

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

Nitrofurantoin-induced pulmonary fibrosis: a case report. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

[Pulmonary fibrosis secondary to nitrofurantoin]. [2013]

5. Switzerland 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. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Influence of flocculating agents and structural vehicles on the physical stability and rheological behavior of nitrofurantoin suspension. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

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

Nitrofurantoin failure in males with an uncomplicated urinary tract infection: a primary care observational cohort study. [2023]

10. Austria pubmed.ncbi.nlm.nih.gov

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