Menopause, Postmenopausal Symptoms, Postmenopausal Syndrome, Postmenopause, Recurrent Urinary Tract Infection
Conditions
Keywords
recurrent urinary tract infection, genitourinary syndrome of menopause, prasterone
Brief summary
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
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.
Interventions
DRUGPrasterone
Nightly intravaginal prasterone insert (6.5 mg prasterone at a concentration of 0.50%) for 24 weeks.
DRUGPlacebo
Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks.
Sponsors
AMAG Pharmaceuticals, Inc.
Olivia Cardenas-Trowers, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of urinary tract infections (UTIs) | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean days of antibiotic use | 12 weeks and 24 weeks | Average number of days of antibiotic use for participants in each treatment group who develop a UTI. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in treatment response as measured by the percentage of superficial cells in the maturation index of the vaginal smear | Baseline, 12 weeks, and 24 weeks | Histological laboratory evaluation. |
| Change from baseline in treatment response as measured by the percentage of intermediate cells in the maturation index of the vaginal smear | Baseline, 12 weeks, and 24 weeks | Histological laboratory evaluation. |
| Change from baseline in treatment response as measured by the Vulvovaginal Symptom Questionnaire (VSQ) | Baseline, 12 weeks, and 24 weeks | 21 items with four scales: symptoms, emotions, life impact, and sexual impact. Total scores range: 0-21 (higher scores suggestive of greater severity of symptoms). |
| Change from baseline in treatment response as measured by the vaginal pH | Baseline, 12 weeks, and 24 weeks | pH test strip. |
| Change from baseline in treatment response as measured by the Overactive bladder questionnaire (OAB-q) | Baseline, 12 weeks, and 24 weeks | Total scores range: 0-100 (higher scores on the symptom-severity scale suggestive of greater severity of symptoms and higher scores on the quality-of-life scale suggestive of better quality of life). |
| Change from baseline in treatment response as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) | Baseline, 12 weeks, and 24 weeks | Three items on frequency, amount of leakage, and overall impact. Scoring 0-21, higher values indicating increasing severity. |
| Number of participants with at least one adverse event | 12 weeks and 24 weeks | Adverse events will only be those determined to be related to the study drug. |
| Change from baseline in treatment response as measured by the self-reported most bothersome symptom (MBS) | Baseline, 12 weeks, and 24 weeks | Via a questionnaire, patient rates symptoms of GSM that she experiences. The highest ranked symptom is the patient's MBS. |
| Change from baseline in treatment response as measured by the percentage of parabasal cells in the maturation index of the vaginal smear | Baseline, 12 weeks, and 24 weeks | Histological laboratory evaluation. |
Countries
United States
Outcome results
None listed