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

June 25, 2021 updated by: Olivia Cardenas-Trowers, M.D.

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Louisville, Kentucky, United States, 40205
        • University of Louisville Urogynecology at Springs Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intravaginal prasterone insert
Nightly intravaginal prasterone insert for 24 weeks
Drug: Prasterone
Nightly intravaginal prasterone insert (6.5 mg prasterone at a concentration of 0.50%) for 24 weeks.
Other Names:
  • Intrarosa
  • DHEA
  • Dehydroepiandrosterone
Placebo Comparator: Intravaginal placebo insert (Witepsol H-15)
Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks
Drug: Placebo
Nightly intravaginal placebo insert (Witepsol H-15, a mix of synthetic triglycerides) for 24 weeks.
Other Names:
  • Witepsol H-15
  • Witepsol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of urinary tract infections (UTIs)
Time Frame: 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.
12 weeks
Incidence of urinary tract infections (UTIs)
Time Frame: 24 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.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean days of antibiotic use
Time Frame: 12 weeks and 24 weeks
Average number of days of antibiotic use for participants in each treatment group who develop a UTI.
12 weeks and 24 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in treatment response as measured by the vaginal pH
Time Frame: Baseline, 12 weeks, and 24 weeks
pH test strip.
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
Time Frame: Baseline, 12 weeks, and 24 weeks
Histological laboratory evaluation.
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
Time Frame: Baseline, 12 weeks, and 24 weeks
Histological laboratory evaluation.
Baseline, 12 weeks, and 24 weeks
Change from baseline in treatment response as measured by the percentage of intermediate cells in the maturation index of the vaginal smear
Time Frame: Baseline, 12 weeks, and 24 weeks
Histological laboratory evaluation.
Baseline, 12 weeks, and 24 weeks
Change from baseline in treatment response as measured by the Vulvovaginal Symptom Questionnaire (VSQ)
Time Frame: 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).
Baseline, 12 weeks, and 24 weeks
Change from baseline in treatment response as measured by the self-reported most bothersome symptom (MBS)
Time Frame: 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.
Baseline, 12 weeks, and 24 weeks
Change from baseline in treatment response as measured by the Overactive bladder questionnaire (OAB-q)
Time Frame: 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).
Baseline, 12 weeks, and 24 weeks
Change from baseline in treatment response as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF)
Time Frame: Baseline, 12 weeks, and 24 weeks
Three items on frequency, amount of leakage, and overall impact. Scoring 0-21, higher values indicating increasing severity.
Baseline, 12 weeks, and 24 weeks
Number of participants with at least one adverse event
Time Frame: 12 weeks and 24 weeks
Adverse events will only be those determined to be related to the study drug.
12 weeks and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Olivia Cardenas-Trowers, M.D.

Collaborators

AMAG Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Olivia Cardenas-Trowers, M.D., University of Louisville
  • Principal Investigator: Sean L. Francis, M.D., University of Louisville

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 1, 2020

Primary Completion (Anticipated)

February 1, 2021

Study Completion (Anticipated)

February 1, 2021

Study Registration Dates

First Submitted

February 24, 2019

First Submitted That Met QC Criteria

February 24, 2019

First Posted (Actual)

February 26, 2019

Study Record Updates

Last Update Posted (Actual)

June 30, 2021

Last Update Submitted That Met QC Criteria

June 25, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19.0075

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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