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

164 Participants Needed

Trial Summary

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 evidence supports the effectiveness of the drug methenamine hippurate for preventing urinary tract infections?

Research shows that methenamine hippurate can significantly reduce the number of urinary tract infections in girls, from 3.1 infections per year to 0.7, and similar benefits are being explored in women. This suggests it may be a useful alternative to antibiotics for preventing these infections. ^{1 2 3 4 5}

Is methenamine hippurate safe for humans?

Methenamine hippurate has been used in studies for preventing urinary tract infections, and it generally appears safe with no significant side effects reported, except for some complaints about taste. It was better tolerated than another common treatment, nitrofurantoin, which caused nausea in some patients. ^{1 2 3 5 6}

How does the drug methenamine hippurate differ from other treatments for preventing urinary tract infections?

Methenamine hippurate is unique because it acts as a urinary antiseptic, which helps prevent urinary tract infections (UTIs) without using antibiotics. This makes it a useful alternative for people who want to avoid the side effects and resistance issues associated with long-term antibiotic use. ^{1 2 3 5 7}

What is the purpose of this trial?

The goal of this clinical trial is to compare methenamine hippurate prophylaxis to routine antibiotic prophylaxis following onabotulinumtoxinA (BOTOX-A) injections in women with overactive bladder (OAB). Participants will be randomly selected to receive one of the two post-procedural prophylaxis medications. The primary outcome measure will be urinary tract infection (UTI) rates within 30 days from the BOTOX-A procedure. Secondary outcomes will assess patient satisfaction with the two post-procedural prophylaxis medications.

Research Team

Vivian Sung, MD, MPH

Principal Investigator

Women & Infants Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

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

Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU). [2023]

2. England 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. [2022]

3. Sweden pubmed.ncbi.nlm.nih.gov

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

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

The resurgence of methenamine hippurate in the prevention of recurrent UTIs in women- a systematic review. [2023]

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

Methenamine Prophylaxis for Recurrent Urinary Tract Infections in a Tertiary Referral Center. [2023]

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

Prevention of recurrent urinary infections in women: a comparative trial between nitrofurantoin and methenamine hippurate. [2019]

7. Sweden pubmed.ncbi.nlm.nih.gov

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