Methenamine hippurate 1g tablets

OBJECTIVE To investigate the preventive effect of the antiseptic methenamine hippurate on recurrent urinary tract infections (rUTIs) in older women. METHODS Triple-blind, randomised, placebo-controlled phase IV trial with a six-month treatment period and a six-month follow-up. Women ≥ 70 years with rUTIs were recruited from general practice in Norway, Sweden, Poland, and The Netherlands. Recruitment started December 2019, with follow-up completed at the end of June 2023. Participants were randomised to methenamine hippurate 1g x 2 or placebo 1 tablet x 2 for six months. The primary outcome was number of antibiotic treatments for UTIs during the treatment period. Secondary outcomes included number of antibiotic treatments for UTIs during the follow-up period, UTI symptom severity and episode duration. Differences in complications were measured as safety outcomes. RESULTS Of 289 recruited women, 281 (97%) were included in the main analysis (140 in the methenamine hippurate group, 141 in the placebo group). During the treatment period, the methenamine hippurate group had a lower incidence of antibiotic treatments for UTIs than the placebo group, with an incidence rate ratio of 0.75 (95% CI 0.57-1.0, p= 0.049). In the follow-up period, the ratio was reversed: The methenamine hippurate group had a higher incidence of antibiotic treatments for UTIs than the placebo group, with an incidence rate ratio of 1.7 (95% CI 1.3-2.3, p<0.001). There were no important differences in UTI symptom severity/duration or complications between the groups. CONCLUSION Methenamine hippurate reduces the frequency of rUTIs in older women with a point estimate of a 25% reduction, suggesting advantages over low-dose antibiotic prophylaxis due to its low potential for selection for antimicrobial resistance and mild side effects. However, discontinuation after six-month treatment duration seems to increase the risk of UTI relapses, and physicians should be aware of this risk when initiating or discontinuing treatment. TRIAL REGISTRATION ClinicalTrials.gov Registry (NCT04077580); EudraCT: 2018-002235.

Abstract licence: CC BY