Back to resultsClinical Trial on the Preventive Effect of Intravaginal Prasterone on Recurrent Urinary Tract Infections in Postmenopausal Women
Primary Purpose
Recurrent Urinary Tract Infection, Postmenopause, Postmenopausal Syndrome
Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Prasterone
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Recurrent Urinary Tract Infection focused on measuring recurrent urinary tract infection, genitourinary syndrome of menopause, prasterone
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)
Sites / Locations
- University of Louisville Urogynecology at Springs Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Intravaginal prasterone insert
Intravaginal placebo insert (Witepsol H-15)
Arm Description
Nightly intravaginal prasterone insert for 24 weeks
Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Mean days of antibiotic use
Average number of days of antibiotic use for participants in each treatment group who develop a UTI.
Full Information
NCT ID
NCT03854396
First Posted
February 24, 2019
Last Updated
June 25, 2021
Sponsor
Olivia Cardenas-Trowers, M.D.
Collaborators
AMAG Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03854396
Brief Title
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
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Withdrawn
Why Stopped
due to termination of ISR by PI with agreement by grant sponsor
Study Start Date
May 2020 (Anticipated)
Primary Completion Date
February 2021 (Anticipated)
Study Completion Date
February 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Olivia Cardenas-Trowers, M.D.
Collaborators
AMAG Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Urinary Tract Infection, Postmenopause, Postmenopausal Syndrome, Postmenopausal Symptoms, Menopause
Keywords
recurrent urinary tract infection, genitourinary syndrome of menopause, prasterone
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravaginal prasterone insert
Arm Type
Active Comparator
Arm Description
Nightly intravaginal prasterone insert for 24 weeks
Arm Title
Intravaginal placebo insert (Witepsol H-15)
Arm Type
Placebo Comparator
Arm Description
Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Prasterone
Other Intervention Name(s)
Intrarosa, Dehydroepiandrosterone, DHEA
Intervention Description
Nightly intravaginal prasterone insert (6.5 mg prasterone at a concentration of 0.50%) for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Witepsol H-15, Witepsol
Intervention Description
Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks.
Primary Outcome Measure Information:
Title
Incidence of urinary tract infections (UTIs)
Description
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.
Time Frame
12 weeks
Title
Incidence of urinary tract infections (UTIs)
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Mean days of antibiotic use
Description
Average number of days of antibiotic use for participants in each treatment group who develop a UTI.
Time Frame
12 weeks and 24 weeks
Other Pre-specified Outcome Measures:
Title
Change from baseline in treatment response as measured by the vaginal pH
Description
pH test strip.
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Change from baseline in treatment response as measured by the percentage of parabasal cells in the maturation index of the vaginal smear
Description
Histological laboratory evaluation.
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Change from baseline in treatment response as measured by the percentage of superficial cells in the maturation index of the vaginal smear
Description
Histological laboratory evaluation.
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Change from baseline in treatment response as measured by the percentage of intermediate cells in the maturation index of the vaginal smear
Description
Histological laboratory evaluation.
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Change from baseline in treatment response as measured by the Vulvovaginal Symptom Questionnaire (VSQ)
Description
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).
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Change from baseline in treatment response as measured by the self-reported most bothersome symptom (MBS)
Description
Via a questionnaire, patient rates symptoms of GSM that she experiences. The highest ranked symptom is the patient's MBS.
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Change from baseline in treatment response as measured by the Overactive bladder questionnaire (OAB-q)
Description
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).
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Change from baseline in treatment response as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF)
Description
Three items on frequency, amount of leakage, and overall impact. Scoring 0-21, higher values indicating increasing severity.
Time Frame
Baseline, 12 weeks, and 24 weeks
Title
Number of participants with at least one adverse event
Description
Adverse events will only be those determined to be related to the study drug.
Time Frame
12 weeks and 24 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivia Cardenas-Trowers, M.D.
Organizational Affiliation
University of Louisville
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sean L. Francis, M.D.
Organizational Affiliation
University of Louisville
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville Urogynecology at Springs Medical Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40205
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified raw data and other supporting materials will be made available to approved investigators. Email requests to olivia.cardenas-trowers@louisville.edu.
IPD Sharing Time Frame
Data will be available beginning 1 month and ending 24 months following article publication.
IPD Sharing 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.
Citations:
PubMed Identifier
24484571
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.
Results Reference
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PubMed Identifier
29369839
Citation
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.
Results Reference
background
PubMed Identifier
6730943
Citation
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.
Results Reference
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PubMed Identifier
25415166
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.
Results Reference
background
PubMed Identifier
25160739
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.
Results Reference
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PubMed Identifier
30554531
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.
Results Reference
background
PubMed Identifier
26731686
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.
Results Reference
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PubMed Identifier
23954500
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.
Results Reference
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PubMed Identifier
25771041
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, 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.
Results Reference
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Clinical Trial on the Preventive Effect of Intravaginal Prasterone on Recurrent Urinary Tract Infections in Postmenopausal Women
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