Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections

Study Overview
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Brief Summary
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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.

Official Title
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Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections: TAPER (Techniques of APplying Vaginal Estrogen for Prevention of Recurrent Urinary Tract Infections) Trial

Conditions
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Recurrent Urinary Tract Infection

Intervention / Treatment
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* Drug: Periurethral application of estradiol cream
* Drug: Intravaginal application of estradiol cream


Participation Criteria
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Eligibility Criteria
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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 History of or at high risk for estrogen-dependent malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravaginal Estrogen Application<br>Intravaginal application of 1 gram estradiol cream at bedtime twice a week for 6 months | Drug: Intravaginal application of estradiol cream<br>* The control group will apply 1 gram estradiol cream intravaginally using an applicator.<br>|
| Experimental: Periurethral Estrogen Application<br>Periurethral application of 0.5 gram estradiol cream at bedtime twice a week for 6 months | Drug: Periurethral application of estradiol cream<br>* The experimental group will apply estradiol cream in a different location (periurethral) and at a smaller dose (0.5 gram) compared to the control group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to urinary tract infection | Time to first urinary tract infection after initiation of study intervention | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urinary symptoms at 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 | Baseline, 6 months | 
| Change from baseline in vaginal symptoms at 6 months | Questionnaire assessment of vaginal symptoms and bother using 5-point Likert scale, developed by research team | Baseline, 6 months | 
| Change from baseline in sexual function at 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. | Baseline, 6 months | 
| Amount of estrogen cream used | Estradiol cream tubes will be weighed at each research visit in grams | 6 months | 
| Participant experience with use of estrogen cream | Questionnaire assessment of patient experience using 5-point Likert and open-ended questions, developed by the research team | 6 months | 
| Change from baseline in vaginal pH at 6 months | Assessment using pH strips during pelvic examination | Baseline, 6 months | 
| Change from baseline in vaginal maturation index at 6 months | Assessment of vaginal cell types using a superficial swab, collected from proximal vagina | Baseline, 6 months | 
| Change from baseline in Vaginal and urinary Lactobacillus levels at 6 months | Clean catch urine and vaginal swab sample collection with quantification of Lactobacillus | Baseline, 6 months | 
| Change from baseline in Vaginal and urinary E. coli levels at 6 months | Clean catch urine and vaginal swab sample collection for quantification of E. coli | Baseline, 6 months |