Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections (TAPER)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Urinary Tract Infection
• Intervention / Treatment: Drug: Intravaginal application of estradiol cream; Drug: Periurethral application of estradiol cream

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Stephanie W Zuo, MD; Phone Number: 412-270-4818; Email: zuos@upmc.edu
• Study Contact Backup: Name: Lindsey Baranski; Phone Number: 412-641-7894; Email: baranskil@mail.magee.edu

Study Locations

• United States
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Recruiting
      • UPMC Lemieux Sports Complex
      • Contact: Lindsey Baranski
    • Erie, Pennsylvania, United States, 16550
      • Recruiting
      • UPMC Hamot
      • Contact: Linda Paterniti
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Medical Center-Magee Womens Hospital
      • Contact: Lindsey Baranski
    • Pittsburgh, Pennsylvania, United States, 15237
      • Recruiting
      • UPMC Passavant-McCandless
      • Contact: Lindsey Baranski

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravaginal Estrogen Application; Intravaginal application of 1 gram estradiol cream at bedtime twice a week for 6 months	Drug: Intravaginal application of estradiol cream; The control group will apply 1 gram estradiol cream intravaginally using an applicator.
Experimental: Periurethral Estrogen Application; Periurethral application of 0.5 gram estradiol cream at bedtime twice a week for 6 months	Drug: Periurethral application of estradiol cream; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants who are UTI-free at 6 months	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

Collaborators and Investigators

• Sponsor: Stephanie Wang Zuo
• Investigators: Principal Investigator: Stephanie W Zuo, MD, University of Pittsburgh Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2023
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: July 21, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Recurrence; Urinary Tract Infections; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: STUDY22010147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No