Recurrent Urinary Tract InfectionPhase 4NCT05723601
Preference of Women With Recurrent Urinary Tract Infection for Vaginal Estradiol Tablet vs Cream
A Phase 4 study testing Estradiol vaginal cream and Estradiol Vaginal Tablet in people with Recurrent Urinary Tract Infection, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
Vaginally applied estrogen has been shown to decrease the incidence of Recurrent Urinary Tract Infection (rUTI) in post-menopausal women. However, prior studies have shown the compliance rate for topical estrogen cream is low. Read more about this study
- Who is it for?
- Ages 20 to 80 years, women only
- Conditions the study is for
- Recurrent Urinary Tract Infection
- What is being tested?
- Estradiol vaginal cream and Estradiol Vaginal Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2024to Jan 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 20 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women age 20-80 who are post-menopausal or have undergone surgical menopause. Post-menopausal defined as amenorrhea for ≥ 1 year, or surgical menopause through bilateral oophorectomy, or menopausal symptoms for ≥ 1 year in women with prior hysterectomy
- New or previous diagnosis of recurrent Urinary Tract Infections (rUTI) (3 or more UTIs in the past year or 2 or more UTIs in the last 6 months) Must have at least one culture documented UTI, the remaining can be documented by urinalysis showing nitrites and leukocyte esterase.
- Not currently taking daily prophylactic antibiotics
- Willing to use vaginal estrogen for prevention of recurrent UTIs
Who cannot join
- Interstitial cystitis or bladder pain syndrome, nephrolithiasis, genitourinary abnormalities, fistula, history of renal transplant or anatomic abnormality of the kidney
- Fecal incontinence, intermittent catheterization or indwelling catheter, poorly controlled DM, urothelial cancer, estrogen-sensitive cancer including active breast cancer
- Recent urologic surgery within 3 months
- Inability to retain vaginal tablet (ex due to advanced prolapse, history of colpocleisis)
- Other medical reasons that are deemed incompatible with vaginal estrogen treatment
- Use of vaginal estrogen in the past 1 month- patients can be recruited after a 1 month wash-out period
Show all 9Show fewer
- Inability to follow up at clinic study site to give sample, for example due to transportation issues
- Organ transplant patients
- Patients on systemic hormone replacement therapy (HRT)
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Addressing Preference as a Patient-centered Outcome to Prevent Recurrent Urinary Tract Infection (rUTI) in Post-menopausal Women: a Cross-over Randomized Controlled Trial
Vaginally applied estrogen has been shown to decrease the incidence of Recurrent Urinary Tract Infection (rUTI) in post-menopausal women. However, prior studies have shown the compliance rate for topical estrogen cream is low. The vaginal estradiol tablet has been shown to be preferred by patients being treated for genitourinary syndrome of menopause and has improved compliance. There are no studies looking at the preference of post-menopausal women with rUTI for vaginal estradiol tablet as an alternative to vaginal estradiol cream.
Read the detailed description
This study is a cross-over randomized study to assess preference. Participants will be in the study for 6 months, they will use vaginal estradiol cream for 3 months and vaginal estradiol tablet for 3 months. Patients who meet diagnostic criteria for rUTI will be recruited. Group A participants will start with 3 months of cream and then switch to tablets. Group B will start with 3 months of tablets and switch to cream. In addition, participants may be started on other supplemental medications (Cranberry, D-mannose, methenamine) at the discretion of their provider. Patients will get monthly phone calls to assess for side effects, safety concerns, and symptoms of UTI.
- Conditions
- Recurrent Urinary Tract Infection
- Being tested
- Estradiol vaginal cream, Estradiol Vaginal Tablet
- Keywords
- vaginal estradiol cream, vaginal estradiol tablet
- 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.
Estradiol vaginal creamDrug
Participants will use vaginal estradiol cream for 3 months
Estradiol Vaginal TabletDrug
Participants will use vaginal estradiol tablet for 3 months
| Study group | Role | What they receive |
|---|---|---|
| cream used first and then switch to tablets | Active comparator | participants will start with 3 months of cream and then switch to tablets Receives: Drug: Estradiol vaginal cream; Drug: Estradiol Vaginal Tablet |
| tablets used first and switch to cream | Active comparator | participants will start with 3 months of tablets and switch to cream Receives: Drug: Estradiol vaginal cream; Drug: Estradiol Vaginal Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient preference rate for vaginal estradiol cream versus tablet
Preference will be assess at 6 months or at the time of withdrawal, by asking participants: "Which route of vaginal estrogen do you prefer: Vaginal estradiol tablet or vaginal estradiol cream?"
Measured: month 6
Secondary outcomes (3)
Change in vaginal and urinary microbiome Lactobacillus amount with the use of vaginal estradiol tablet versus cream
Vaginal culture swab and urine culture specimens will be collected - The specimens will be sent for species-specific polymerase chain reaction (PCR) for Lactobacillus
Measured: Baseline, Month 3, and Month 6
Change in overall satisfaction, convenience, side effects, and effectiveness of vaginal estradiol cream vs tablet using Treatment Satisfaction Questionnaire for Medication (TSQM)
Treatment Satisfaction Questionnaire for Medication (TSQM) - The TSQM domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain. A questionnaire assessing adherence and the reasons for not taking drug at the recommended frequency of administration.
Measured: Month 3 and Month 6
Changes in adherence scores
Adherence will be assessed by the medication adherence questionnaire (MAQ) - The MAQ will be used to determine medication adherence. This questionnaire asks respondents about past experience in taking medications. The responses are 'yes' or 'no' and are scored as yes=1 and no=0. Scores will be summed: high adherence = score of 0 points; medium adherence = score of 1-2 points, and low adherence = score of 3-4 points. Means and standard deviations will be compared within and between groups.
Measured: Month 3 and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start12 Jan 2024
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Recurrent Urinary Tract InfectionStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Candace Parker-Autry, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05723601
- Sponsor's protocol ID
- IRB00092892
- Status last verified
- Dec 2025
- First submitted
- 1 Feb 2023
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No data will be shared with other researchers
Publications
Walters, M.D. and M.M. Karram, Urogynecology and Pelvic Reconstructive surgery. 2022: Mosby Elsevier.
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 23526171Ferrante KL, Wasenda EJ, Jung CE, Adams-Piper ER, Lukacz ES. Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial. Female Pelvic Med Reconstr Surg. 2021 Feb 1;27(2):112-117. doi: 10.1097/SPV.0000000000000749.
PubMed 31232721Raz 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 8350884Boris S, Suarez JE, Vazquez F, Barbes C. Adherence of human vaginal lactobacilli to vaginal epithelial cells and interaction with uropathogens. Infect Immun. 1998 May;66(5):1985-9. doi: 10.1128/IAI.66.5.1985-1989.1998.
PubMed 9573080O'Hanlon DE, Moench TR, Cone RA. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One. 2013 Nov 6;8(11):e80074. doi: 10.1371/journal.pone.0080074. eCollection 2013.
PubMed 24223212Anger J, Lee U, Ackerman AL, Chou R, Chughtai B, Clemens JQ, Hickling D, Kapoor A, Kenton KS, Kaufman MR, Rondanina MA, Stapleton A, Stothers L, Chai TC. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. J Urol. 2019 Aug;202(2):282-289. doi: 10.1097/JU.0000000000000296. Epub 2019 Jul 8.
PubMed 31042112Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001500. doi: 10.1002/14651858.CD001500.pub2.
PubMed 17054136Eriksen 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 10329858Weissmann-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 27648663Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015 Apr;40(4):277-83.
PubMed 25859123Dason S, Dason JT, Kapoor A. Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can Urol Assoc J. 2011 Oct;5(5):316-22. doi: 10.5489/cuaj.11214. No abstract available.
PubMed 22031610Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986 Jan;24(1):67-74. doi: 10.1097/00005650-198601000-00007.
PubMed 3945130Atkinson MJ, Sinha A, Hass SL, Colman SS, Kumar RN, Brod M, Rowland CR. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004 Feb 26;2:12. doi: 10.1186/1477-7525-2-12.
PubMed 14987333Rioux JE, Devlin MC, Gelfand MM, Steinberg WM, Hepburn DS. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2018 Nov;25(11):1208-1213. doi: 10.1097/GME.0000000000001220.
PubMed 30358715
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addressing Preference as a Patient-centered Outcome to Prevent Recurrent Urinary Tract Infection (rUTI) in Post-menopausal Women: a Cross-over Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05723601
- Acronym / sponsor ID
- IRB00092892
- Conditions
- Recurrent Urinary Tract Infection
- Keywords
- vaginal estradiol cream, vaginal estradiol tablet
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 12 Jan 2024 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 10 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vaginally applied estrogen has been shown to decrease the incidence of Recurrent Urinary Tract Infection (rUTI) in post-menopausal women. However, prior studies have shown the compliance rate for topical estrogen cream is low. The vaginal estradiol tablet has been shown to be preferred by patients being treated for genitourinary syndrome of menopause and has improved compliance. There are no studies looking at the preference of post-menopausal women with rUTI for vaginal estradiol tablet as an alternative to vaginal estradiol cream.
Detailed description
This study is a cross-over randomized study to assess preference. Participants will be in the study for 6 months, they will use vaginal estradiol cream for 3 months and vaginal estradiol tablet for 3 months. Patients who meet diagnostic criteria for rUTI will be recruited. Group A participants will start with 3 months of cream and then switch to tablets. Group B will start with 3 months of tablets and switch to cream. In addition, participants may be started on other supplemental medications (Cranberry, D-mannose, methenamine) at the discretion of their provider. Patients will get monthly phone calls to assess for side effects, safety concerns, and symptoms of UTI.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cream used first and then switch to tablets | Active comparator | Drug: Estradiol vaginal cream, Drug: Estradiol Vaginal Tabletparticipants will start with 3 months of cream and then switch to tablets |
| tablets used first and switch to cream | Active comparator | Drug: Estradiol vaginal cream, Drug: Estradiol Vaginal Tabletparticipants will start with 3 months of tablets and switch to cream |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Women age 20-80 who are post-menopausal or have undergone surgical menopause. Post-menopausal defined as amenorrhea for ≥ 1 year, or surgical menopause through bilateral oophorectomy, or menopausal symptoms for ≥ 1 year in women with prior hysterectomy
- New or previous diagnosis of recurrent Urinary Tract Infections (rUTI) (3 or more UTIs in the past year or 2 or more UTIs in the last 6 months) Must have at least one culture documented UTI, the remaining can be documented by urinalysis showing nitrites and leukocyte esterase.
- Not currently taking daily prophylactic antibiotics
- Willing to use vaginal estrogen for prevention of recurrent UTIs
Key exclusion criteria (9 listed)
- Interstitial cystitis or bladder pain syndrome, nephrolithiasis, genitourinary abnormalities, fistula, history of renal transplant or anatomic abnormality of the kidney
- Fecal incontinence, intermittent catheterization or indwelling catheter, poorly controlled DM, urothelial cancer, estrogen-sensitive cancer including active breast cancer
- Recent urologic surgery within 3 months
- Inability to retain vaginal tablet (ex due to advanced prolapse, history of colpocleisis)
- Other medical reasons that are deemed incompatible with vaginal estrogen treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Estradiol vaginal creamParticipants will use vaginal estradiol cream for 3 months | Drug | cream used first and then switch to tablets, tablets used first and switch to cream |
| Estradiol Vaginal TabletParticipants will use vaginal estradiol tablet for 3 months | Drug | cream used first and then switch to tablets, tablets used first and switch to cream |
Primary outcome
Patient preference rate for vaginal estradiol cream versus tablet
Time frame: month 6
Preference will be assess at 6 months or at the time of withdrawal, by asking participants: "Which route of vaginal estrogen do you prefer: Vaginal estradiol tablet or vaginal estradiol cream?"
3 secondary outcomes
Change in vaginal and urinary microbiome Lactobacillus amount with the use of vaginal estradiol tablet versus cream
Time frame: Baseline, Month 3, and Month 6
Change in overall satisfaction, convenience, side effects, and effectiveness of vaginal estradiol cream vs tablet using Treatment Satisfaction Questionnaire for Medication (TSQM)
Time frame: Month 3 and Month 6
Changes in adherence scores
Time frame: Month 3 and Month 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- BackgroundWalters, M.D. and M.M. Karram, Urogynecology and Pelvic Reconstructive surgery. 2022: Mosby Elsevier.
- Background: PubMed 23526171Minkin 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.
- Background: PubMed 31232721Ferrante KL, Wasenda EJ, Jung CE, Adams-Piper ER, Lukacz ES. Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial. Female Pelvic Med Reconstr Surg. 2021 Feb 1;27(2):112-117. doi: 10.1097/SPV.0000000000000749.
- Background: PubMed 8350884Raz 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.
- Background: PubMed 9573080Boris S, Suarez JE, Vazquez F, Barbes C. Adherence of human vaginal lactobacilli to vaginal epithelial cells and interaction with uropathogens. Infect Immun. 1998 May;66(5):1985-9. doi: 10.1128/IAI.66.5.1985-1989.1998.
- Background: PubMed 24223212O'Hanlon DE, Moench TR, Cone RA. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One. 2013 Nov 6;8(11):e80074. doi: 10.1371/journal.pone.0080074. eCollection 2013.
- Background: PubMed 31042112Anger J, Lee U, Ackerman AL, Chou R, Chughtai B, Clemens JQ, Hickling D, Kapoor A, Kenton KS, Kaufman MR, Rondanina MA, Stapleton A, Stothers L, Chai TC. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. J Urol. 2019 Aug;202(2):282-289. doi: 10.1097/JU.0000000000000296. Epub 2019 Jul 8.
- Background: PubMed 17054136Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001500. doi: 10.1002/14651858.CD001500.pub2.
- Background: PubMed 10329858Eriksen 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.
- Background: PubMed 27648663Weissmann-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.
- Background: PubMed 25859123Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015 Apr;40(4):277-83.
- Background: PubMed 22031610Dason S, Dason JT, Kapoor A. Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can Urol Assoc J. 2011 Oct;5(5):316-22. doi: 10.5489/cuaj.11214. No abstract available.
- Individual participant dataSharing planned: No. No data will be shared with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Candace Parker-Autry, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Estradiol vaginal cream and Estradiol Vaginal Tablet in people with Recurrent Urinary Tract Infection, run by Wake Forest University Health Sciences 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 4 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 2 Dec 2025. 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?
Patient preference rate for vaginal estradiol cream versus tablet (time frame: month 6). 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 NCT05723601, which also lists 15 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 2 Dec 2025.