Clinical trial NCT03854396: Clinical Trial on the Preventive Effect of Intravaginal Prasterone on Recurrent Urinary Tract Infections in Postmenopausal Women
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Recurrent Urinary Tract Infection
Postmenopause
Postmenopausal Syndrome
Postmenopausal Symptoms
Menopause
Keywords: recurrent urinary tract infection
genitourinary syndrome of menopause
prasterone
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: AMAG Pharmaceuticals, Inc.
First posted: 2019-02-26
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of urinary tract infections (UTIs)
timeFrame: 12 weeks
measure: Incidence of urinary tract infections (UTIs)
timeFrame: 24 weeks
Secondary outcomes:
measure: Mean days of antibiotic use
timeFrame: 12 weeks and 24 weeks
Other outcomes:
measure: Change from baseline in treatment response as measured by the vaginal pH
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Change from baseline in treatment response as measured by the percentage of parabasal cells in the maturation index of the vaginal smear
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Change from baseline in treatment response as measured by the percentage of superficial cells in the maturation index of the vaginal smear
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Change from baseline in treatment response as measured by the percentage of intermediate cells in the maturation index of the vaginal smear
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Change from baseline in treatment response as measured by the Vulvovaginal Symptom Questionnaire (VSQ)
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Change from baseline in treatment response as measured by the self-reported most bothersome symptom (MBS)
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Change from baseline in treatment response as measured by the Overactive bladder questionnaire (OAB-q)
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Change from baseline in treatment response as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF)
timeFrame: Baseline, 12 weeks, and 24 weeks
measure: Number of participants with at least one adverse event
timeFrame: 12 weeks and 24 weeks
Locations:
city: Louisville
country: United States
facility: University of Louisville Urogynecology at Springs Medical Center
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Olivia Cardenas-Trowers, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Louisville
name: Sean L. Francis, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Portman DJ, Goldstein SR, Kagan R. Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review. Climacteric. 2019 Feb;22(1):65-72. doi: 10.1080/13697137.2018.1535583. Epub 2018 Dec 17.
citation: Labrie F, Archer DF, Koltun W, Vachon A, Young D, Frenette L, Portman D, Montesino M, Cote I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur E; VVA Prasterone Research Group. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016 Mar;23(3):243-56. doi: 10.1097/GME.0000000000000571.
citation: Labrie F, Martel C, Berube R, Cote I, Labrie C, Cusan L, Gomez JL. Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol. 2013 Nov;138:359-67. doi: 10.1016/j.jsbmb.2013.08.002. Epub 2013 Aug 14.
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