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Recurrent Urinary Tract InfectionPhase 4NCT06353269

Adherence to Vaginal Estrogen Therapy in Hypoestrogenic Women With Recurrent Urinary Tract Infections

A Phase 4 study testing Estring Vaginal Product, Vagifem and Estrace 0.01% Vaginal Cream in people with Recurrent Urinary Tract Infection and Hypoestrogenism, run by University of California, Irvine at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The goal of this clinical trial is to learn about medication adherence to difference types of vaginal estrogen in women with low levels of estrogen (for example, post-menopausal women) who have recurrent urinary tract infections. Medication adherence means whether patients take their medicine as prescribed. Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
What is being tested?
Estring Vaginal Product, Vagifem and Estrace 0.01% Vaginal Cream
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
1 siteUnited States
Study dates
14 Jun 2024to Sep 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • female, at least 18 years old with diagnosis of hypoestrogenism (defined by post-menopausal status of 12 months or more of amenorrhea, history of bilateral salpingo-oophorectomy) AND recurrent UTI as defined by greater than or equal to 3 in 1 year or 2 in 6 months by positive urine culture or clinically suspected UTI)

Who cannot join

  • Have a known etiology of infections (urologic stones, fistulas, fecal incontinence, catheterization, or poorly controlled diabetes - Hgb A1C cutoff of 8)
  • Contraindication to vaginal estrogen (actively treated estrogen-sensitive tumor, allergies to medication formulation, inability to apply or place vaginal estrogen of any modality)
  • Suspected mesh complications or voiding problems from pelvic reconstructive surgery
  • Short vaginal length (less than 7cm) or poor dexterity or mobility that may prevent use of estrogen ring
  • Do not speak English
  • For the nested cohort only - patients currently using vaginal estrogen greater than 2x per month
Show all 9Show fewer
  • Deferral criteria:
  • Undiagnosed hematuria or vaginal bleeding; however enrollment may proceed after negative workup for malignancy
  • Remote history of estrogen-sensitive tumor: enrollment allowed after approval by oncologist or primary care physician

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of California Irvine Medical Center

    Orange, California, 92868

Other trials in United States

About this study

  • The goal of this clinical trial is to learn about medication adherence to difference types of vaginal estrogen in women with low levels of estrogen (for example, post-menopausal women) who have recurrent urinary tract infections. Medication adherence means whether patients take their medicine as prescribed.
  • Another goal of the study is to learn about changes to the skin of the vagina before and after estrogen treatment, using a specialized imaging modality called optical coherence tomography, which is similar to receiving an ultrasound.
  • A third goal of the study is to learn about changes to the microbiome (all the bacteria that naturally live in our bodies) before and after treatment with vaginal estrogen. The researchers will be looking specifically at the microbiome in the urine and the vagina.

Participants will be assigned by chance (like the flip of a coin) to receive one of three possible vaginal estrogen treatments - cream, tablets, or drug-eluting ring.

Read more
  • The main study tests and procedures include an initial visit in which the researchers will collect baseline information about participants and have participants complete a series of questionnaires.
  • There will then be 3 and 6 month follow-ups in which the researchers will have participants complete additional questionnaires and the researchers also assess whether participants are using the vaginal estrogen treatment that you were prescribed.

If a participant is part of the microbiome cohort, they will also be asked to do the following:

  • a baseline visit in which urinary and vaginal specimens are collected to assess their baseline microbiome. The vaginal specimen collection will involve a q-tip swab inside the vagina; it is similar to a pap smear.
  • Finally, participants will have an imaging modality performed on their vagina called optical coherence tomography, which allows the researchers to assess the thickness of the vaginal walls and the blood vessel density. This imaging modality involves the insertion of a thin probe into the vagina to obtain the images of the vaginal wall.
  • These tests will then be repeated at 6 months to assess if vaginal estrogen treatment causes changes to the vagina.
Being tested
Estring Vaginal Product, Vagifem, Estrace 0.01% Vaginal Cream
Keywords
vaginal estrogen
Medical subject headings
Urinary Tract Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Estring Vaginal ProductDrug

    estradiol vaginal ring, exchanged every 12 weeks

  • VagifemDrug

    vaginal estrogen tablet, used twice per week

  • Estrace 0.01% Vaginal CreamDrug

    vaginal estrogen cream, used twice per week

Study groups in NCT06353269
Study groupRoleWhat they receive
Estrogen creamExperimentalParticipants in this arm will receive the vaginal estrogen cream (Estrace 0.01%) for treatment. Participants will apply 0.5gm twice per week for the duration of the study.
Receives: Drug: Estrace 0.01% Vaginal Cream
Estrogen tabletExperimentalParticipants in this arm will receive the vaginal estrogen tablets (Vagifem) for treatment. Participants will place one tablet (10 mcg) into the vagina twice per week for the duration of the study.
Receives: Drug: Vagifem
Estrogen drug-eluting ringExperimentalParticipants in this arm will receive the vaginal estrogen drug-eluting ring (Estring) for treatment. Participants will have the ring placed by a provider at their clinical visit. The ring will be exchanged every 12 weeks.
Receives: Drug: Estring Vaginal Product

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adherence to vaginal estrogen treatment

    The primary outcome will be the adherence to vaginal estrogen treatment at the 6 month follow-up visit. The 6 month follow-up visit will be the endpoint of the study. The investigators will consider both subjective, patient-reported adherence at 6 months, as well as objective data - tube weight for the estrogen cream, number of tablets left for the estrogen tables, and presence or absence of drug-eluting ring on physical exam for the estrogen ring.

    Measured: 6 month follow-up visit

Secondary outcomes (12)
  1. UTI rates

    number of culture-proven urinary tract infections

    Measured: the 6 month duration of the study

  2. validated patient questionnaire - Urinary Distress Inventory Short Form (UDI-6)

    Urinary Distress Inventory Short Form (UDI-6) - six questions, scored from 0 (not at all) to 3 (greatly), with higher scores indicating more distress from urinary symptoms.

    Measured: Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

  3. validated patient questionnaires - UTI Symptoms Assessment Questionnaire (UTISA)

    UTI Symptoms Assessment Questionnaire (UTISA) - 15 questions, rated from 0 (did not have/not at all) to 3 (severe/a lot), with higher scores indicating a more symptomatic UTI

    Measured: Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

  4. validated patient questionnaires - Treatment Satisfaction with Medications Questionnaire (SATMED-Q)

    Treatment Satisfaction with Medications Questionnaire (SATMED-Q) - 17 questions, scored from 0 (not at all) to 4 (very much), with higher scores indicating greater satisfaction with medical treatment.

    Measured: Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

  5. validated patient questionnaires - Patient Global Impression of Improvement Questionnaire (PGI-I)

    Patient Global Impression of Improvement Questionnaire (PGI-I) - one-question with scores from 1 (very much better) to 7 (very much worse0, with higher scores indicating a worsening in symptoms after treatment.

    Measured: Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

  6. validated patient questionnaires - Medication Adherence Report Scale (MARS-5)

    Medication Adherence Report Scale (MARS-5) - 5 questions, rated from 1 (always) to 5 (never), with a higher score indicating lower medication adherence.

    Measured: Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

  7. optical coherence tomography measurements for nested OCT cohort - vaginal epithelial thickness

    changes to vaginal epithelial thickness (VET) before and after treatment as measured by vaginal optical coherence tomography (OCT).

    Measured: baseline and 6 month follow-up visits

  8. optical coherence tomography measurements for nested OCT cohort - blood vessel density

    changes to blood vessel density (BVD) before and after treatment as measured by vaginal optical coherence tomography (OCT).

    Measured: baseline and 6 month follow-up visits

  9. Vaginal health index for nested microbiome cohort

    vaginal health index (VHI) before and after treatment - The Vaginal Health Index Score is a clinical tool that, by evaluating 5 parameters (vaginal elasticity, vaginal secretions, pH, epithelial mucous membrane, vaginal hydration), allows to obtain a final score defining the degree of atrophy in the genitourinary tract by assigning a single score to each parameter. Total score ranges from 5 to 25, with lower scores corresponding to greater urogenital atrophy

    Measured: baseline and 6 month follow-up visits

  10. Vaginal maturation index for nested microbiome cohort

    vaginal maturation index (VMI) before and after treatment - microscopic evaluation of the ratio of vaginal epithelial cells (parabasal, intermediate and superficial)

    Measured: baseline and 6 month follow-up visits

  11. Urologic microbiome results for nested microbiome cohort

    Urologic microbiome before and after treatment (Lactobacillus abundance processed by Zymo analysis).

    Measured: baseline and 6 month follow-up visits

  12. Vaginal microbiome results for nested microbiome cohort

    Vaginal microbiome before and after treatment (Lactobacillus abundance processed by Zymo analysis).

    Measured: baseline and 6 month follow-up visits

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2024
  2. Study start14 Jun 2024
  3. Primary completionJun 2027 (estimated)
  4. Study completionSep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Health services research
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
111 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06353269
Sponsor's protocol ID
4255
Status last verified
Jun 2026
First submitted
28 Feb 2024
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002 Jul 8;113 Suppl 1A:5S-13S. doi: 10.1016/s0002-9343(02)01054-9.

    PubMed 12113866
  • Tan-Kim J, Shah NM, Do D, Menefee SA. Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. Am J Obstet Gynecol. 2023 Aug;229(2):143.e1-143.e9. doi: 10.1016/j.ajog.2023.05.002. Epub 2023 May 11.

    PubMed 37178856
  • Perrotta C, Aznar M, Mejia R, Albert X, Ng CW. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Obstet Gynecol. 2008 Sep;112(3):689-90. doi: 10.1097/AOG.0b013e318185f7a5. No abstract available.

    PubMed 18757671
  • Brubaker L, Carberry C, Nardos R, Carter-Brooks C, Lowder JL. American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract Infection in Adult Women. Female Pelvic Med Reconstr Surg. 2018 Sep/Oct;24(5):321-335. doi: 10.1097/SPV.0000000000000550. No abstract available.

    PubMed 29369839
  • Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6. doi: 10.1056/NEJM199309093291102.

    PubMed 8350884
  • Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol. 1999 May;180(5):1072-9. doi: 10.1016/s0002-9378(99)70597-1.

    PubMed 10329858
  • Portman D, Shulman L, Yeaw J, Zeng S, Uzoigwe C, Maamari R, Iyer NN. One-year treatment persistence with local estrogen therapy in postmenopausal women diagnosed as having vaginal atrophy. Menopause. 2015 Nov;22(11):1197-203. doi: 10.1097/GME.0000000000000465.

    PubMed 25944522
  • Minkin MJ, Maamari R, Reiter S. Improved compliance and patient satisfaction with estradiol vaginal tablets in postmenopausal women previously treated with another local estrogen therapy. Int J Womens Health. 2013;5:133-9. doi: 10.2147/IJWH.S41897. Epub 2013 Mar 15.

    PubMed 23526171
  • Weissmann-Brenner A, Bayevsky T, Yoles I. Compliance to vaginal treatment-tablets versus cream: a retrospective 9 years study. Menopause. 2017 Jan;24(1):73-76. doi: 10.1097/GME.0000000000000729.

    PubMed 27648663
  • Rioux JE, Devlin C, Gelfand MM, Steinberg WM, Hepburn DS. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000 May-Jun;7(3):156-61. doi: 10.1097/00042192-200007030-00005.

    PubMed 10810960

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Estring Vaginal Product, Vagifem and Estrace 0.01% Vaginal Cream in people with Recurrent Urinary Tract Infection and Hypoestrogenism, run by University of California, Irvine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adherence to vaginal estrogen treatment (time frame: 6 month follow-up visit). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06353269, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.

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