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

Menopause Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03854396
• Other study ID #: 19.0075
• Status: Withdrawn
• Phase: Phase 3
• Start date: May 2020
• Est. completion date: February 2021

Study information

• Verified date: June 2021
• Source: University of Louisville
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Menopause
• Postmenopausal Symptoms
• Postmenopausal Syndrome
• Postmenopause
• Recurrent Urinary Tract Infection
• Syndrome
• Urinary Tract Infections

Intervention

Drug:
• Prasterone
Nightly intravaginal prasterone insert (6.5 mg prasterone at a concentration of 0.50%) for 24 weeks.
• Placebo
Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks.

Locations

Country	Name	City	State
United States	University of Louisville Urogynecology at Springs Medical Center	Louisville	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Olivia Cardenas-Trowers, M.D.	AMAG Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (9)

Brubaker L, Carberry C, Nardos R, Carter-Brooks C, Lowder JL. American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract Infection in Adult Women. Female Pelvic Med Reconstr Surg. 2018 Sep/Oct;24(5):321-335. doi: 10.1097/SPV.0000000000000550. — View Citation

Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014 Mar;28(1):1-13. doi: 10.1016/j.idc.2013.09.003. Epub 2013 Dec 8. Review. — View Citation

Iosif CS, Bekassy Z. Prevalence of genito-urinary symptoms in the late menopause. Acta Obstet Gynecol Scand. 1984;63(3):257-60. — View Citation

Labrie F, Archer DF, Bouchard C, Girard G, Ayotte N, Gallagher JC, Cusan L, Baron M, Blouin F, Waldbaum AS, Koltun W, Portman DJ, Côté I, Lavoie L, Beauregard A, Labrie C, Martel C, Balser J, Moyneur É; Members of the VVA Prasterone Group. Prasterone has parallel beneficial effects on the main symptoms of vulvovaginal atrophy: 52-week open-label study. Maturitas. 2015 May;81(1):46-56. doi: 10.1016/j.maturitas.2015.02.005. Epub 2015 Feb 16. — View Citation

Labrie F, Archer DF, Koltun W, Vachon A, Young D, Frenette L, Portman D, Montesino M, Côté I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur É; 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. — View Citation

Labrie F, Martel C, Bérubé R, Côté 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. — View Citation

Portman DJ, Gass ML; Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society. Menopause. 2014 Oct;21(10):1063-8. doi: 10.1097/GME.0000000000000329. — View 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. Review. — View Citation

Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in treatment response as measured by the vaginal pH	pH test strip.	Baseline, 12 weeks, and 24 weeks
Other	Change from baseline in treatment response as measured by the percentage of parabasal cells in the maturation index of the vaginal smear	Histological laboratory evaluation.	Baseline, 12 weeks, and 24 weeks
Other	Change from baseline in treatment response as measured by the percentage of superficial cells in the maturation index of the vaginal smear	Histological laboratory evaluation.	Baseline, 12 weeks, and 24 weeks
Other	Change from baseline in treatment response as measured by the percentage of intermediate cells in the maturation index of the vaginal smear	Histological laboratory evaluation.	Baseline, 12 weeks, and 24 weeks
Other	Change from baseline in treatment response as measured by the Vulvovaginal Symptom Questionnaire (VSQ)	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).	Baseline, 12 weeks, and 24 weeks
Other	Change from baseline in treatment response as measured by the self-reported most bothersome symptom (MBS)	Via a questionnaire, patient rates symptoms of GSM that she experiences. The highest ranked symptom is the patient's MBS.	Baseline, 12 weeks, and 24 weeks
Other	Change from baseline in treatment response as measured by the Overactive bladder questionnaire (OAB-q)	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).	Baseline, 12 weeks, and 24 weeks
Other	Change from baseline in treatment response as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF)	Three items on frequency, amount of leakage, and overall impact. Scoring 0-21, higher values indicating increasing severity.	Baseline, 12 weeks, and 24 weeks
Other	Number of participants with at least one adverse event	Adverse events will only be those determined to be related to the study drug.	12 weeks and 24 weeks
Primary	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
Primary	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	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