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

NCT03854396 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: 19.0075
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Urinary Tract Infection; Postmenopause; Postmenopausal Syndrome; Postmenopausal Symptoms; Menopause

Keywords

recurrent urinary tract infection; genitourinary syndrome of menopause; prasterone

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Mean days of antibiotic use

  12 weeks and 24 weeks

Other Outcomes (9)

• Change from baseline in treatment response as measured by the vaginal pH

  Baseline, 12 weeks, and 24 weeks

• 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

• 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

Study Arms (2)

Intravaginal prasterone insert

ACTIVE COMPARATOR

Nightly intravaginal prasterone insert for 24 weeks

Drug: Prasterone

Intravaginal placebo insert (Witepsol H-15)

PLACEBO COMPARATOR

Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks

Drug: Placebo

Interventions

Prasterone DRUG

Nightly intravaginal prasterone insert (6.5 mg prasterone at a concentration of 0.50%) for 24 weeks.

Also known as: Intrarosa, Dehydroepiandrosterone, DHEA

Intravaginal prasterone insert

Placebo DRUG

Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks.

Also known as: Witepsol H-15, Witepsol

Intravaginal placebo insert (Witepsol H-15)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Olivia Cardenas-Trowers, M.D.: lead
• AMAG Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Louisville Urogynecology at Springs Medical Center

Louisville, Kentucky, 40205, United States

Location

Related Publications (9)

• 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.

  PMID: 24484571 BACKGROUND

• 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. No abstract available.

  PMID: 29369839 BACKGROUND

• Iosif CS, Bekassy Z. Prevalence of genito-urinary symptoms in the late menopause. Acta Obstet Gynecol Scand. 1984;63(3):257-60. doi: 10.3109/00016348409155509.

  PMID: 6730943 BACKGROUND

• 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.

  PMID: 25415166 BACKGROUND

• 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.

  PMID: 25160739 BACKGROUND

• 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.

  PMID: 30554531 BACKGROUND

• 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.

  PMID: 26731686 BACKGROUND

• 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.

  PMID: 23954500 BACKGROUND

• Labrie F, Archer DF, Bouchard C, Girard G, Ayotte N, Gallagher JC, Cusan L, Baron M, Blouin F, Waldbaum AS, Koltun W, Portman DJ, Cote I, Lavoie L, Beauregard A, Labrie C, Martel C, Balser J, Moyneur E; 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.

  PMID: 25771041 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

Dehydroepiandrosterone; witepsol

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Olivia Cardenas-Trowers, M.D.

  University of Louisville

  PRINCIPAL INVESTIGATOR

• Sean L. Francis, M.D.

  University of Louisville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Fellow Physician in Female Pelvic Medicine & Reconstructive Surgery

Study Record Dates

• First Submitted: February 24, 2019
• First Posted: February 26, 2019
• Study Start: May 1, 2020
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: June 30, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available beginning 1 month and ending 24 months following article publication.
• Access Criteria: Available to investigators whose proposed use of the data is for individual participant data meta-analysis and has been approved by an independent review committee for this purpose. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)