Clinical Trial on the Preventive Effect of Intravaginal Prasterone on Recurrent Urinary Tract Infections in Postmenopausal Women

Study Overview
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Brief Summary
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Urinary tract infections (UTIs) are bothersome and more likely to occur in postmenopausal women. Frequent UTIs, as well as other problems with the urinary and genital systems such as painful sex and urinary frequency/urgency, are part of a symptom complex called genitourinary syndrome of menopause (GSM). Prasterone (Intrarosa®) is a man-made steroid that helps with painful sex in postmenopausal women. Because previous studies have shown prasterone to help with other GSM problems, this study was designed to investigate if prasterone used in the vagina decreases the number of UTIs in postmenopausal women.

Detailed Description
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Urinary tract infections (UTIs) are costly contributing to more than 8 million ambulatory visits (84% women) in the United States in 2007. Recurrent urinary tract infections (rUTIs) are UTIs diagnosed on at least 2 urine cultures in 6 months, or at least 3 in 1 year. The incidence of rUTIs increases in menopause with an estimated 10-15% of women > 60 years old having rUTIs. rUTIs contribute to a constellation of bothersome genitourinary symptoms in some postmenopausal women called genitourinary syndrome of menopause (GSM). Thus, menopause, rUTIs, and GSM are intimately linked. Prasterone (Intrarosa®) is a synthetic version of the steroid, dehydroepiandrosterone (DHEA), approved by the US Food and Drug Administration in 2016 for the treatment of moderate to severe dyspareunia due to GSM. Large, prospective studies have shown prasterone to safely decrease vaginal pH, decrease parabasal cells, increase superficial cells, and decrease symptoms related to atrophy like dyspareunia in women with GSM. Given prasterone's favorable treatment effects on some GSM symptoms, investigation of prasterone as a possible treatment option for rUTIs in the setting of GSM is warranted. This is a single center, double-blind, placebo-controlled, randomized trial comparing the efficacy of nightly intravaginal prasterone for 24 weeks to intravaginal placebo in decreasing rUTIs in women with GSM. The study hypothesis is that intravaginal prasterone decreases UTI incidence in women with GSM compared to placebo.

Official Title
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A Randomized, Double-blind, Placebo-controlled Trial on the Preventive Effect of Intravaginal Prasterone (DHEA, Intrarosa®) on Recurrent Urinary Tract Infections in Women With Genitourinary Syndrome of Menopause

Conditions
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Recurrent Urinary Tract Infection, Postmenopause, Postmenopausal Syndrome, Postmenopausal Symptoms, Menopause

Intervention / Treatment
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* Drug: Prasterone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 years or older who are ≥ 1 year after spontaneous or surgical (bilateral oophorectomy) menopause Presence of ≤ 5% of superficial cells on vaginal smear and vaginal pH > 5.0 History of ≥ 2 UTIs in 6 months or ≥ 3 UTIs in 12 months (with documentation of a UTI confirmed on urine culture within the past 1 year) Negative urine culture prior to treatment randomization Exclusion Criteria: Known allergy/hypersensitivity to prasterone or its constituents Contraindications to estrogen: acute thrombophlebitis, history of blood clotting disorder, and/or personal history of thromboembolic disorder associated with estrogen use Known or suspected estrogen-dependent neoplasms or mammary, ovarian, cervical, or vaginal malignancies Known congenital urologic or gynecologic abnormality Chronic immunosuppression Need for chronic catheterization Vaginal bleeding of origin other than vaginal mucosal atrophy Vaginal infection requiring treatment Use of systemic hormone replacement therapy or estrogen within past 6 months Use of topical estrogen within past 3 months Consistent use of vaginal products (lubricants, douches) Ongoing antibiotic treatment Ongoing treatment with Lactobacillus Inability to comply with protocol or place vaginal insert with applicator appropriately Less than 3 months status post urinary incontinence and/or pelvic organ prolapse surgery Unable to speak or read English If an exclusion condition is resolved, the patient may be re-approached later for study recruitment (ie., genitourinary infection, use of antibiotics, etc)

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravaginal prasterone insert<br>Nightly intravaginal prasterone insert for 24 weeks | Drug: Prasterone<br>* Nightly intravaginal prasterone insert (6.5 mg prasterone at a concentration of 0.50%) for 24 weeks.<br>* Other names: DHEA;|
| Placebo Comparator: Intravaginal placebo insert (Witepsol H-15)<br>Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks | Drug: Placebo<br>* Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks.<br>* Other names: Witepsol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of urinary tract infections (UTIs) | Rate of UTIs during the study with UTI defined as at least one symptom of UTI (eg., dysuria, urinary frequency/urgency/incontinence, hematuria) and at least ≥10^2 colony-forming units (CFUs)/mL of 1 or more uropathogens on urine culture. | 12 weeks | 
| Incidence of urinary tract infections (UTIs) | Rate of UTIs during the study with UTI defined as at least one symptom of UTI (eg., dysuria, urinary frequency/urgency/incontinence, hematuria) and at least ≥10^2 colony-forming units (CFUs)/mL of 1 or more uropathogens on urine culture. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean days of antibiotic use | Average number of days of antibiotic use for participants in each treatment group who develop a UTI. | 12 weeks and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent urinary tract infection, genitourinary syndrome of menopause, prasterone