Methenamine Hippurate for Preventing Urinary Tract Infections

(META Trial)

Overseen By Kyle Wohlrab, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Women and Infants Hospital of Rhode Island

Must not be taking: Methenamine, Antibiotics

Disqualifiers: Male, Neurogenic bladder, Bladder cancer, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods to prevent urinary tract infections (UTIs) after BOTOX-A injections for women with overactive bladder. It compares a common antibiotic treatment with methenamine hippurate, a different type of medication. Researchers aim to determine which method better prevents UTIs and which participants prefer. Women receiving BOTOX-A injections for bladder issues may qualify if they are not already using methenamine hippurate or antibiotics. As a Phase 4 trial, the treatment is FDA-approved and proven effective, allowing researchers to understand its benefits for 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 be taking antibiotics on the day of the BOTOX-A procedure.

What is the safety track record for these treatments?

Research has shown that methenamine hippurate is generally safe and well-tolerated for preventing urinary tract infections (UTIs). Studies indicate it can effectively reduce the frequency of UTIs without antibiotics. One review found methenamine to be a good option for avoiding antibiotics while still preventing UTIs. Another study showed that methenamine works as well as traditional antibiotics in preventing recurring UTIs.

Methenamine is well-received by patients, with few reports of side effects. It has been successfully used in different groups, including older adults, for UTI prevention. Overall, evidence suggests methenamine is a safe choice for those wanting to avoid antibiotics when preventing UTIs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard of care for preventing urinary tract infections, which typically involves various oral antibiotics, methenamine hippurate offers a unique approach. This treatment works by turning urine into an environment that's hostile to bacteria, thanks to its ability to release formaldehyde in the urinary tract. Researchers are excited about methenamine hippurate because it targets the problem differently than traditional antibiotics, potentially reducing the risk of antibiotic resistance and offering an alternative for those who can't tolerate standard antibiotics. Also, its effectiveness over a short, three-day course makes it a promising, convenient option for patients.

What evidence suggests that methenamine hippurate might be an effective treatment for preventing UTIs?

Research has shown that methenamine hippurate, which participants in this trial may receive, is a strong option for preventing urinary tract infections (UTIs). Studies indicate it works as well as antibiotics in reducing UTIs and can lower the number of repeat UTIs by about 25%. This makes it a safe and effective choice without the need for antibiotics. Methenamine hippurate is easy to tolerate and offers a promising alternative for preventing UTIs. ^{1 5 6 7 8}

Who Is on the Research Team?

Vivian Sung, MD, MPH

Principal Investigator

Women & Infants Hospital

Are You a Good Fit for This Trial?

This trial is for women with overactive bladder (OAB) who are receiving BOTOX-A injections. Participants should not have any conditions that would exclude them from the study, but specific exclusion criteria were not provided.

Inclusion Criteria

I am receiving BOTOX injections for overactive bladder in a doctor's office.

Exclusion Criteria

I need a catheter before a procedure.

I have been diagnosed with Interstitial Cystitis or Painful Bladder Syndrome.

I have had bladder cancer in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either methenamine hippurate or typical antibiotic prophylaxis for three days following BOTOX-A injections

3 days

Follow-up

Participants are monitored for urinary tract infection rates and medication satisfaction

30 days

Survey Completion

Participants complete the FACIT-TS-G survey assessing medication satisfaction over the phone

Completed >30 days after BOTOX-A injection

What Are the Treatments Tested in This Trial?

Interventions

• Methenamine Hippurate

Trial Overview The trial is testing if methenamine hippurate can prevent urinary tract infections as effectively as typical antibiotics after BOTOX-A injections for OAB. Women will be randomly given one of these medications and monitored for UTI rates within 30 days post-procedure.

How Is the Trial Designed?

Group I: Methenamine hippurate prophylaxis Experimental Treatment 1 Intervention

Participants in the experimental arm will receive methenamine hippurate 1 gram by mouth twice daily for three days.

Group II: Typically prescribed oral antibiotic prophylaxis Active Control 1 Intervention

Typically prescribed oral antibiotic prophylaxis for the purposes of this study is defined as oral antibiotics that are routinely prescribed following BOTOX-A injections for UTI prophylaxis. Given known heterogeneity in antibiotic prophylaxis type and duration as well as the lack of standardized antibiotic recommendations for intradetrusor BOTOX-A injections, the choice of antibiotic prophylaxis is deferred to the physician performing the BOTOX-A injections. The duration of treatment will be standardized to three days, based off previous studies.

Who Is Running the Clinical Trial?

Women and Infants Hospital of Rhode Island

Lead Sponsor

Trials

119

Recruited

59,200+

Published Research Related to This Trial

In a study of 20 girls aged 5-12 with recurrent urinary tract infections, treatment with methenamine hippurate (Hiprex) for 12 months significantly reduced the average number of infections from 3.1 to 0.7 per year (p < 0.001).

After stopping the treatment, the infection rate increased to 1.4 per year, indicating that methenamine hippurate is effective for long-term prevention of urinary tract infections, with minimal side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term prophylaxis with methenamine hippurate in girls with recurrent urinary tract infections. Petersen, S.[2019]

In a trial involving 240 women with recurrent urinary tract infections, methenamine hippurate was found to be non-inferior to daily low-dose antibiotics in preventing symptomatic infections, with an incidence of 1.38 episodes per person year compared to 0.89 for antibiotics.

Both treatment groups reported similar rates of mild adverse reactions (24% for antibiotics and 28% for methenamine hippurate), suggesting that methenamine hippurate could be a safe alternative for antibiotic prophylaxis in managing recurrent urinary tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial. Harding, C., Mossop, H., Homer, T., et al.[2022]

This study is a randomized, controlled trial involving 400 women aged 70 and older, aimed at assessing the efficacy of methenamine hippurate in reducing recurrent urinary tract infections (UTIs) over a 6-month treatment period.

The primary outcome is the number of antibiotic treatments for UTIs during the treatment phase, with safety outcomes also being monitored, which will help determine the long-term safety and effectiveness of methenamine hippurate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU). Heltveit-Olsen, SR., Sundvall, PD., Gunnarsson, R., et al.[2023]

In a study of 24 patients treated with methenamine hippurate for an average of 16 months, the number of urinary tract infection reinfections was reduced by about two-thirds in patients who achieved abacteriuria, indicating its efficacy as a prophylactic treatment.

Methenamine hippurate was found to have limited effectiveness in treating established urinary tract infections, suggesting that it should be used primarily for prevention after achieving abacteriuria, as no significant side effects or complications, such as urinary calculus or renal function deterioration, were observed during the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with methenamine hippurate in recurrent urinary tract infection. Nilsson, S.[2019]

Methenamine hippurate (MH) demonstrated high success rates in preventing recurrent uncomplicated urinary tract infections (UTIs) in women, with an 83% success rate in premenopausal women and 77% in postmenopausal women over a 6-month period.

The study involved 162 women and found that success rates were not significantly affected by factors like age or diabetes, but patients using intermittent catheterization had lower success rates, indicating a need for further research to optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methenamine Prophylaxis for Recurrent Urinary Tract Infections in a Tertiary Referral Center. Wade, C., Lacy, ME., Harris, L., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39955521/

Effectiveness of methenamine hippurate in preventing ... Our meta-analysis provides evidence supporting methenamine hippurate as an effective, non-inferior and safe prophylactic option for preventing recurrent UTIs ...

2. bmcurol.biomedcentral.com bmcurol.biomedcentral.com/articles/10.1186/s12894-025-01708-8

Effectiveness of methenamine hippurate in preventing urinary ... Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1198743X25003441

Methenamine hippurate as prophylaxis for recurrent ... Methenamine hippurate reduces the frequency of rUTIs in older women with a point estimate of a 25% reduction, suggesting advantages over low-dose antibiotic ...

4. evidence.nihr.ac.uk evidence.nihr.ac.uk/alert/methenamine-as-good-as-antibiotics-preventing-urinary-tract-infections/

Methenamine is as good as antibiotics at preventing UTIs after 12 months, both treatments similarly reduced urinary tract infections; on average, women in the methenamine group reported marginally more ...

5. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2895

Methenamine for urinary tract infection prophylaxis: A ... This systematic review suggests methenamine generally appears to be an effective and well-tolerated antibiotic-sparing option for UTI prophylaxis.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6551271/

Safety and Efficacy of Methenamine Hippurate for the ... We found that methenamine is well tolerated and is useful in reducing UTI, antibiotic prescriptions, and hospitalization in RTR with recurrent UTI.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06810687

Is Methenamine Prophylaxis for Urinary Tract Infection After ... Methenamine has been shown to be non-inferior to antibiotic prophylaxis in the setting of recurrent UTI. Methenamine has most commonly been used ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6759703/

Evaluation of methenamine for urinary tract infection ... The available data, however, suggest that methenamine may be a safe and effective drug for the prevention of UTI in older adults with adequate ...