Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections

Phase 2

Active, not recruiting

• Conditions: Recurrent Urinary Tract Infection
• Interventions: Drug: Periurethral application of estradiol cream; Drug: Intravaginal application of estradiol cream

• Registration Number: NCT05472779
• Lead Sponsor: Stephanie Wang Zuo

Brief Summary

Due to rising antibiotic resistance, there has been a focus on non-antibiotic prophylactic measures for postmenopausal patients with recurrent urinary tract infections (rUTI), one of which is the safe and efficacious option of vaginal estrogen therapy. Standard application of vaginal estrogen cream entails intravaginal application of the cream twice a week, but some providers counsel patients with rUTI to apply a small, pea-sized amount to the periurethral area. This ideally reduces the amount of vaginal estrogen used while attaining a similar effect. However, to date, there is no data to prove that the periurethral technique of application is similar or non-inferior to intravaginal application in preventing UTI.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-21
• Study First Submitted QC: 2022-07-21
• Study First Posted: 2022-07-25
• Study Start: 2023-01-03
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-17
• Primary Completion: 2025-04-30
• Study Completion: 2025-05-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 114

Inclusion Criteria

• Postmenopausal (definition: No menses for 1 or more years or surgical menopause (bilateral oophorectomy). If there is a past history of hysterectomy, patient must be age 56 or older (95th percentile for age at menopause) or have laboratory evidence of menopause (ie. FSH >30))
• Meets criteria for recurrent urinary tract infections (UTIs) with 2 or more UTI in 6 months or 3 or more UTI in 1 year
• May include patients who used vaginal estrogen previously if they have stopped use for 3 or more months prior to inclusion into study.
• Patients must be recommended vaginal estrogen as part of normal clinical care for prevention of recurrent UTI

Exclusion Criteria

• Current use of vaginal or oral estrogen products
• Inability or refusal to use vaginal estrogen
• Daily antibiotic use
• Significant vaginal stenosis (eg. due to lichen sclerosis, radiation or obliterative prolapse surgery) that would prohibit use of a vaginal applicator (ie. genital hiatus <1cm)
• Inability to use vaginal applicator and without caregiver who can administer (eg. provider-managed pessary use, significant arthritis)
• Frequent (1x weekly or more frequent) use of bladder instillations containing an antibiotic
• Known hydronephrosis as a result of incomplete bladder emptying
• Use of intermittent or indwelling urinary catheterization
• Known bladder stones, mesh erosion into bladder, or foreign object in bladder
• Unable to consent for self
• Active treatment for an estrogen-dependent malignancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Periurethral Estrogen Application	Periurethral application of estradiol cream	Periurethral application of 0.5 gram estradiol cream at bedtime twice a week for 6 months
Intravaginal Estrogen Application	Intravaginal application of estradiol cream	Intravaginal application of 1 gram estradiol cream at bedtime twice a week for 6 months

Primary Outcome Measures

Name	Time	Method
Percentage of participants who are UTI-free at 6 months	6 months

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Vaginal and urinary Lactobacillus levels at 6 months	Baseline, 6 months	Clean catch urine and vaginal swab sample collection with quantification of Lactobacillus
Change from baseline in vaginal symptoms at 6 months	Baseline, 6 months	Questionnaire assessment of vaginal symptoms and bother using 5-point Likert scale, developed by research team
Participant experience with use of estrogen cream	6 months	Questionnaire assessment of patient experience using 5-point Likert and open-ended questions, developed by the research team
Change from baseline in urinary symptoms at 6 months	Baseline, 6 months	Questionnaire assessment of urinary symptoms and symptom distress (Urogenital Distress Inventory, Short Form), total score range 0-100 with higher numbers representing worse urinary symptoms
Change from baseline in sexual function at 6 months	Baseline, 6 months	Questionnaire assessment of sexual function (Female Sexual Function Index-6) with scores ranging from 2 to 30, with 19 and below denoting sexual dysfunction.
Amount of estrogen cream used	6 months	Estradiol cream tubes will be weighed at each research visit in grams
Change from baseline in vaginal pH at 6 months	Baseline, 6 months	Assessment using pH strips during pelvic examination
Change from baseline in vaginal maturation index at 6 months	Baseline, 6 months	Assessment of vaginal cell types using a superficial swab, collected from proximal vagina
Change from baseline in Vaginal and urinary E. coli levels at 6 months	Baseline, 6 months	Clean catch urine and vaginal swab sample collection for quantification of E. coli

Trial Locations

Locations (4)

UPMC Lemieux Sports Complex; 🇺🇸 Cranberry Township, Pennsylvania, United States

UPMC Hamot; 🇺🇸 Erie, Pennsylvania, United States

University of Pittsburgh Medical Center-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Passavant-McCandless; 🇺🇸 Pittsburgh, Pennsylvania, United States