Methenamine Hippurate versus Antibiotic Prophylaxis for the Management of Recurrent Urinary Tract Infections in Women: A Randomized Controlled Trial

The primary objective is to evaluate the non-inferiority of methenamine hippurate compared to antibiotic prophylaxis in reducing the incidence of symptomatic urinary tract infection in women with recurrent urinary tract infections during a 6-month period. Additionally, the study aims to determine if this non-antibiotic strategy is associated with a lower selection of antimicrobial resistance. 2: Prophylaxis

Secondary objectives include:

• Assessment of symptomatic episodes during a 12-month follow-up period.
• Determination of the incidence of urosepsis, septic shock, and related hospitalizations.
• Evaluation of quality of life, patient satisfaction, and psychosocial impact.
• Monitoring the incidence of adverse events.
• Quantification of total, prophylactic, and therapeutic antibiotic days.
• Characterization of the microbiological profile of pathogens from urine, rectal, and vaginal swabs, including changes in resistance patterns.
• Analysis of changes in vaginal microbiota composition, specifically alpha and beta diversity.
• Subgroup analyses based on immunodepressed status and hormonal stage.

The sponsor did not provide the total number of participants. The study population consists of women between the ages of 18 and 85 years diagnosed with recurrent urinary tract infections. Inclusion is limited to individuals requiring antibiotic prophylaxis due to having experienced at least two urinary tract infection episodes within the previous 6 months, three or more episodes within the past year, or at least one severe episode necessitating hospitalization during that period. The primary objectives are:

• To evaluate the non-inferiority of methenamine hippurate compared to antibiotic prophylaxis in reducing the frequency of symptomatic UTI episodes over a 6-month period.
• To assess whether methenamine hippurate is associated with a reduced selection of antimicrobial resistance.

This randomized, multicenter, open-label clinical trial is designed to evaluate the clinical and microbiological impact of methenamine hippurate as an alternative prophylaxis for the management of recurrent urinary tract infections in women. The study utilizes a non-inferiority design to compare the test product against various antibiotic prophylaxis options, including cefalexin, sulfamethoxazole/trimethoprim, and fosfomycin trometamol. The research methodology focuses on the primary clinical variable of symptomatic episodes and the primary microbiological variable of multidrug-resistant profiles. The protocol involves a 6-month prophylaxis period followed by a 12-month follow-up period. Study participation begins with a screening visit to confirm eligibility based on specific infection frequency criteria. Subsequent visits are scheduled to monitor the incidence of symptomatic episodes, adverse events, and the occurrence of severe complications such as urosepsis or bacteremia. The overall duration of participant involvement is approximately 18 months, concluding with an end-of-study visit.

Methenamine hippurate is the investigational product administered via the oral route at a dosage of 2 g. This substance is evaluated as a non-antibiotic prophylaxis for the management of recurrent urinary tract infections.

Cefalexin is utilized as a comparator treatment and is administered orally at a dose of 500 mg.

Septrin, containing sulfamethoxazole and trimethoprim, is utilized as a comparator treatment in tablet form at a dose of 400 mg via the oral route.

Fosfomycin trometamol is utilized as a comparator treatment for oral use at a dosage of 0.42 g.

The efficacy of methenamine hippurate as a non-antibiotic prophylaxis for the management of recurrent urinary tract infections is evaluated through several primary endpoints. The primary clinical variable is the total number of symptomatic urinary tract infection episodes recorded during the 6-month treatment period. The primary microbiological variable is the number of patients presenting with isolates exhibiting a multidrug-resistant profile at the 6-month mark.

Secondary efficacy and safety assessments include:

• The number of symptomatic episodes during a 12-month follow-up period.
• The percentage of severe infection episodes, including urosepsis, septic shock, bacteremia, and hospitalizations related to infection during the 6-month treatment and 12-month follow-up periods.
• Patient satisfaction measured using general and infection-specific quality-of-life questionnaires.
• The number of antibiotic courses administered during follow-up.
• The percentage of isolates showing a difficult-to-treat resistance profile, ESBL-producing isolates, or carbapenemase-producing isolates.
• The percentage of alpha and beta diversity within the vaginal microbiota.
• The percentage and intensity of adverse events categorized by organ system.