Recurrent Urinary Tract InfectionPhase 4PRUVENCT05551949
Preventing Recurrent UTI With Vaginal Estrogen
A Phase 4 study testing Vaginal estradiol tablets in people with Recurrent Urinary Tract Infection and Urinary Tract Infections, run by Johns Hopkins University at 1 site in United States.
Trial summary
Among postmenopausal women who suffer from recurrent urinary tract infections (UTI), vaginal estrogen therapy prevents UTI recurrences for 50% of sufferers. This research will investigate why some women benefit but others do not, focusing on (a) the effects of vaginal estrogen therapy on the bacteria that inhabit the… Read more about this study
- Who is it for?
- Ages 55 to 100 years, women only
- Conditions the study is for
- Recurrent Urinary Tract Infection, Urinary Tract Infections, Cystitis Recurrent
- What is being tested?
- Vaginal estradiol tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2022to 31 Aug 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants in this study will be
- Postmenopausal women (menopausal for at least 1 year)
- Minimum age of 55 years
- Participants will have documentation of recurrent UTI, defined as follows:
- History of treatment for at least 3 UTIs in the past year or 2 episodes within 6 months AND
- At least one positive urine culture during an acute symptomatic episode.
Who cannot join
- Women receiving antibiotic prophylaxis to prevent UTI recurrence;
- Women with contraindications to vaginal estrogen (as indicated on the FDA-mandated package insert) and those who have used vaginal or systemic estrogen within the past 6 months;
- Women with an active UTI and those who have received antibiotics within the prior 2 weeks;
- Women with complicated rUTI, defined by immune compromise, anatomic or functional abnormalities of the urinary tract, indwelling catheterization, those performing self-catheterization, and those with neurological disease or illness relevant to the lower urinary tract;
- Women with only asymptomatic bacteriuria (rather than recurrent symptomatic UTI)
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
About this study
Official title: Mechanisms of Successful Vaginal Estrogen Prophylaxis for Postmenopausal Women With Recurrent Urinary Tract Infections: Urogenital Microbiota and Host Immune Responses
Among postmenopausal women who suffer from recurrent urinary tract infections (UTI), vaginal estrogen therapy prevents UTI recurrences for 50% of sufferers. This research will investigate why some women benefit but others do not, focusing on (a) the effects of vaginal estrogen therapy on the bacteria that inhabit the vagina and bladder, (b) its influence on immune responses in both compartments, and (c) the extent to which those changes are critical to successful UTI prevention. The findings will be a first step in the development of more effective strategies to prevent UTI, one of the most common and costly benign urologic conditions.
Read the detailed description
Recurrent urinary tract infections (rUTI) are a significant problem among older women: 13% of female Medicare beneficiaries experience at least one UTI annually and >40% of these develop chronic recurrent UTI. Although UTIs are significantly reduced by vaginal estrogen therapy (VET), 50% of those using VET continue to experience UTI recurrences. It is unknown why some women benefit from VET while others do not. This application focuses on interrogating two mechanisms likely to be central to the effectiveness of VET. The first is the urogenital microbiota: an increase in vaginal lactobacilli is the purported mechanism by which VET reduces rUTI. Important and unanswered questions include how VET influences specific Lactobacillus spp., whether changes to specific Lactobacillus spp are the key to successful prophylaxis, and how VET affects the urinary microbiota. A second mechanism addressed by this application is the host vaginal and urinary immune response. Estrogen appears to influence localized urogenital immune responses, including Th17 and Th1 versus Th2 pathway signaling. Animal studies suggest that these compartmentalized immune responses play a critical role in UTI susceptibility, but human data are lacking. This application will address these unanswered questions. Postmenopausal women with rUTI will be treated with VET. Samples collected before and after VET will characterize vaginal and urinary microbiota, soluble mediators of inflammation in both compartments, and vaginal D-lactic acid. Aims 1 and 2 of this proposal will investigate the impact of VET on the urogenital microbiota and urogenital immune responses, respectively. Aim 3 will characterize the urogenital environments of participants who continue to experience rUTI during VET versus those who remain UTI-free. The accomplishment of these aims will provide pilot data for a larger and more definitive clinical trial. These proposed studies are a key step toward the investigators' goals of identifying biomarkers that reliably predict a successful response to rUTI prophylaxis and ascertaining the biological conditions required for successful UTI prevention. Ultimately, an understanding of the mechanisms of rUTI prevention will allow the development of novel and effective prevention strategies for postmenopausal women suffering from rUTI.
- Being tested
- Vaginal estradiol tablets
- Keywords
- women
- 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.
Vaginal estradiol tabletsDrug
Vaginal estradiol tablets (10mcg).
| Study group | Role | What they receive |
|---|---|---|
| Vaginal estrogen therapy | Other | Participants receive Vaginal estrogen therapy. Receives: Drug: Vaginal estradiol tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Vaginal Microbiota
Changes to relative vaginal abundance of key Lactobacillus spp. before and after treatment.
Measured: Baseline and 12 weeks
Change in Vaginal Interleukin-6 Level
Changes to vaginal Interleukin-6 before and after treatment.
Measured: Baseline and 12 weeks
Change in Urinary Microbiota
Changes to relative urinary abundance of key Lactobacillus spp. before and after treatment.
Measured: Baseline and 12 weeks
Change in Urinary Interleukin-6 Level
Changes to urinary Interleukin-6 before and after treatment.
Measured: Baseline and 12 weeks
Secondary outcomes (1)
Urinary Tract Infection Recurrence
Participants with at least one occurrence of symptomatic UTI after at least 12 weeks of therapy.
Measured: Weeks 12 to 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2022
- Study start1 Jan 2022
- Primary completion30 Jun 2025
- Study completion31 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Urinary Tract InfectionStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Open label, single group clinical trial
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Victoria Handa, MD MHS, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05551949
- Sponsor's protocol ID
- IRB00314740
- Other IDs
- R01DK130856
- Acronym
- PRUVE
- Status last verified
- Feb 2026
- First submitted
- 20 Sep 2022
- Last updated
- 5 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared after study completion
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Successful Vaginal Estrogen Prophylaxis for Postmenopausal Women With Recurrent Urinary Tract Infections: Urogenital Microbiota and Host Immune Responses
- ClinicalTrials.gov ID
- NCT05551949
- Acronym / sponsor ID
- PRUVE / IRB00314740
- Keywords
- women
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- University of Maryland, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 31 Aug 2025 (actual)
- First posted
- 23 Sep 2022 (actual)
- Results
- Posted 5 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Among postmenopausal women who suffer from recurrent urinary tract infections (UTI), vaginal estrogen therapy prevents UTI recurrences for 50% of sufferers. This research will investigate why some women benefit but others do not, focusing on (a) the effects of vaginal estrogen therapy on the bacteria that inhabit the vagina and bladder, (b) its influence on immune responses in both compartments, and (c) the extent to which those changes are critical to successful UTI prevention. The findings will be a first step in the development of more effective strategies to prevent UTI, one of the most common and costly benign urologic conditions.
Detailed description
Recurrent urinary tract infections (rUTI) are a significant problem among older women: 13% of female Medicare beneficiaries experience at least one UTI annually and >40% of these develop chronic recurrent UTI. Although UTIs are significantly reduced by vaginal estrogen therapy (VET), 50% of those using VET continue to experience UTI recurrences. It is unknown why some women benefit from VET while others do not. This application focuses on interrogating two mechanisms likely to be central to the effectiveness of VET. The first is the urogenital microbiota: an increase in vaginal lactobacilli is the purported mechanism by which VET reduces rUTI. Important and unanswered questions include how VET influences specific Lactobacillus spp., whether changes to specific Lactobacillus spp are the key to successful prophylaxis, and how VET affects the urinary microbiota. A second mechanism addressed by this application is the host vaginal and urinary immune response. Estrogen appears to influence localized urogenital immune responses, including Th17 and Th1 versus Th2 pathway signaling. Animal studies suggest that these compartmentalized immune responses play a critical role in UTI susceptibility, but human data are lacking. This application will address these unanswered questions. Postmenopausal women with rUTI will be treated with VET. Samples collected before and after VET will characterize vaginal and urinary microbiota, soluble mediators of inflammation in both compartments, and vaginal D-lactic acid. Aims 1 and 2 of this proposal will investigate the impact of VET on the urogenital microbiota and urogenital immune responses, respectively. Aim 3 will characterize the urogenital environments of participants who continue to experience rUTI during VET versus those who remain UTI-free. The accomplishment of these aims will provide pilot data for a larger and more definitive clinical trial. These proposed studies are a key step toward the investigators' goals of identifying biomarkers that reliably predict a successful response to rUTI prophylaxis and ascertaining the biological conditions required for successful UTI prevention. Ultimately, an understanding of the mechanisms of rUTI prevention will allow the development of novel and effective prevention strategies for postmenopausal women suffering from rUTI.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label, single group clinical trial
| Arm | Type | Receives |
|---|---|---|
| Vaginal estrogen therapy | Other | Drug: Vaginal estradiol tabletsParticipants receive Vaginal estrogen therapy. |
Who may qualify
- Ages
- 55 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participants in this study will be
- Postmenopausal women (menopausal for at least 1 year)
- Minimum age of 55 years
- Participants will have documentation of recurrent UTI, defined as follows:
Key exclusion criteria (5 listed)
- Women receiving antibiotic prophylaxis to prevent UTI recurrence;
- Women with contraindications to vaginal estrogen (as indicated on the FDA-mandated package insert) and those who have used vaginal or systemic estrogen within the past 6 months;
- Women with an active UTI and those who have received antibiotics within the prior 2 weeks;
- Women with complicated rUTI, defined by immune compromise, anatomic or functional abnormalities of the urinary tract, indwelling catheterization, those performing self-catheterization, and those with neurological disease or illness relevant to the lower urinary tract;
- Women with only asymptomatic bacteriuria (rather than recurrent symptomatic UTI)
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 |
|---|---|---|
| Vaginal estradiol tabletsVaginal estradiol tablets (10mcg). | Drug | Vaginal estrogen therapy |
Primary outcome
Change in Vaginal Microbiota
Time frame: Baseline and 12 weeks
Changes to relative vaginal abundance of key Lactobacillus spp. before and after treatment.
Change in Vaginal Interleukin-6 Level
Time frame: Baseline and 12 weeks
Changes to vaginal Interleukin-6 before and after treatment.
Change in Urinary Microbiota
Time frame: Baseline and 12 weeks
Changes to relative urinary abundance of key Lactobacillus spp. before and after treatment.
Change in Urinary Interleukin-6 Level
Time frame: Baseline and 12 weeks
Changes to urinary Interleukin-6 before and after treatment.
1 secondary outcome
Urinary Tract Infection Recurrence
Time frame: Weeks 12 to 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Data will be shared after study completion
Related trials for Recurrent Urinary Tract Infection
Active, not recruitingObservational study
Characterization of Vaginal, Urinary and Fecal Microbiomes in Women With Recurrent Urinary Tract Infections
Urinary Tract Infections, Menopause
Active, not recruiting
Probiotic Supplement for Recurrent UTIs in Healthy Women (L. Plantarum, L. Rhamnosus, B. Lactis)
Recurrent Urinary Tract Infections
RecruitingPhase 3
Evaluate the Efficacy and Safety of U101 Oral Capsules in the Prevention of Uncomplicated rUTIs in Women
Recurrent Urinary Tract Infections in Women
Active, not recruiting
Effect of a Probiotic on the Urinary Tract Microbiota of Participants With Recurrent Urinary Tract Infection.
Recurrent Urinary Tract Infection
RecruitingPhase 4
Topical Steroids to Prevent Recurrent Urinary Tract Infections in Uncircumcised Male Infants: a Pilot Study
Urinary Tract Infection
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.
Victoria Handa, MD MHS principal investigator
Johns Hopkins University
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 Vaginal estradiol tablets in people with Recurrent Urinary Tract Infection and Urinary Tract Infections, run by Johns Hopkins University 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 6 inclusion and 5 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: finished, as of the sponsor's last update on 5 Mar 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?
Yes. Results are posted in the registry (first posted 5 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Vaginal Microbiota (time frame: Baseline and 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Mar 2026.