Methenamine in a Non-antibiotic, Multimodal Approach to UTI Prevention

• Status: Not yet recruiting
• Trial end date: 2021-11-05
• Target enrollment: 0
• Participant gender: Female

Summary

Urinary tract infections (UTIs) are the most common bacterial infection and are especially common in postmenopausal women, who often experience recurrent UTIs. Women with recurrent UTIs are commonly treated with antibiotics, but side effects, collateral damage to commensal bacteria, and antimicrobial resistance result from frequent antibiotic use. It is paramount that researchers develop non-antibiotic treatment strategies for UTIs.

Several non-antibiotic strategies may be successful in preventing recurrent UTIs in postmenopausal women, including low-dose vaginal estrogen, d-mannose, and methenamine hippurate. Methenamine hippurate (MH) is interesting as it causes few side effects, kills bacteria by denaturing bacterial proteins, RNA, and DNA, and does not develop resistance. Several studies have demonstrated the efficacy of daily methenamine on the incidence of UTI. However, women often require multiple therapies in order to prevent recurrence. There are currently few guidelines to help clinicians identify optimal treatment regimens for non-antibiotic prevention of UTI.

The purpose of this pilot study is to examine the feasibility of developing a sequential, multiple assignment, randomization trial (SMART); and examine the treatment effect of MH in combination with vaginal estrogen (VET) and D-mannose on prevention of UTI. The investigators plan to examine the efficacy of the addition of MH to low dose VET and d-mannose in the UTI prevention through randomization to MH + VET + D-mannose vs continuing VET + D-mannose alone. The primary outcome will be the proportion of patients who have symptomatic, culture-proven UTI during a 3 month treatment period. The investigators hypothesize that women on low dose VET, d-mannose, and MH will be less likely to have recurrent UTI than those with VET and d-mannose alone.

This study uses a pragmatic, longitudinal approach that mimics patients' clinical experiences and physicians' decision points during management of UTI prophylaxis. Through this randomized, controlled pilot study, this proposal would allow the investigators to examine the feasibility of conducting a larger-scale, adaptive study trial, and estimate the treatment effect of a non-antibiotic regimen augmented with MH in women who continue to develop recurrence.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Washington University School of Medicine
• Treatments: Estrogens; Methenamine; Methenamine hippurate; Methenamine mandelate

Criteria

Inclusion Criteria:

• Postmenopausal women

• History of recurrent UTI (>=3 culture proven UTIs in one year or >=2 in 6 months)

• Recurrent, culture proven UTI while on vaginal estrogen for at least 4 weeks + d-mannose prophylaxis

• English speaker

Exclusion Criteria:

• Not postmenopausal

• Complicated UTIs

• Known renal tract anomaly

• Liver dysfunction

• Neurogenic bladder

• Incomplete bladder emptying (PVR > 150 cc when voided volume >150 cc)

• Self-catheterization or use of indwelling catheter

• Contraindication to vaginal estrogen, methenamine hippurate, or d-mannose, including allergic reactions

• History of or current endometrial cancer

• History of estrogen sensitive breast cancer without approval of patient, patient's oncologist, oncologic surgeon, or primary care physician to use vaginal estrogen after counseling

• History of interstitial cystitis/painful bladder syndrome

• Urothelial cancer

• Enrolled in other clinical trials for UTIs other than Washington University study IRB# 201711120

• Currently on daily antibiotic prophylaxis and unwilling to stop this intervention