Preference of Women With Recurrent Urinary Tract Infection for Vaginal Estradiol Tablet vs Cream

Study Overview
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Brief Summary
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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
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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.

Official Title
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Addressing Preference as a Patient-centered Outcome to Prevent Recurrent Urinary Tract Infection (rUTI) in Post-menopausal Women: a Cross-over Randomized Controlled Trial

Conditions
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Recurrent Urinary Tract Infection

Intervention / Treatment
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* Drug: Estradiol vaginal cream
* Drug: Estradiol Vaginal Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 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)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: cream used first and then switch to tablets<br>participants will start with 3 months of cream and then switch to tablets | Drug: Estradiol vaginal cream<br>* Participants will use vaginal estradiol cream for 3 months<br>Drug: Estradiol Vaginal Tablet<br>* Participants will use vaginal estradiol tablet for 3 months<br>|
| Active Comparator: tablets used first and switch to cream<br>participants will start with 3 months of tablets and switch to cream | Drug: Estradiol vaginal cream<br>* Participants will use vaginal estradiol cream for 3 months<br>Drug: Estradiol Vaginal Tablet<br>* Participants will use vaginal estradiol tablet for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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? | month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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. | Month 3 and Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaginal estradiol cream, vaginal estradiol tablet