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

Recurrent Urinary Tract Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06353269
• Other study ID #: 4255
• Status: Recruiting
• Phase: Phase 4
• Start date: April 2024
• Est. completion date: October 2027

Study information

• Verified date: April 2024
• Source: University of California, Irvine
• Contact: CHARLOTTE TER HAAR, MD
• Phone: 714-506-6351
• Email: terhaarc[@]hs.uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

• 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.

• 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 111
• Est. completion date: October 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

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

Related Conditions & MeSH terms

• Communicable Diseases
• Hypoestrogenism
• Infections
• Recurrence
• Recurrent Urinary Tract Infection
• Urinary Tract Infections

Intervention

Drug:
• Estring Vaginal Product
estradiol vaginal ring, exchanged every 12 weeks
• Vagifem
vaginal estrogen tablet, used twice per week
• Estrace 0.01% Vaginal Cream
vaginal estrogen cream, used twice per week

Locations

Country	Name	City	State
United States	University of California Irvine Medical Center	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Irvine

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. We 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.	6 month follow-up visit
Secondary	UTI rates	number of culture-proven urinary tract infections	the 6 month duration of the study
Secondary	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.	Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up
Secondary	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	Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up
Secondary	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.	Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up
Secondary	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.	Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up
Secondary	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.	Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up
Secondary	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).	baseline and 6 month follow-up visits
Secondary	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).	baseline and 6 month follow-up visits
Secondary	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	baseline and 6 month follow-up visits
Secondary	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)	baseline and 6 month follow-up visits
Secondary	Urologic microbiome results for nested microbiome cohort	Urologic microbiome before and after treatment (Lactobacillus abundance processed by Zymo analysis).	baseline and 6 month follow-up visits
Secondary	Vaginal microbiome results for nested microbiome cohort	Vaginal microbiome before and after treatment (Lactobacillus abundance processed by Zymo analysis).	baseline and 6 month follow-up visits