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Trial record 29 of 264 for:    Estrogen Resistance

Methenamine in a Non-antibiotic, Multimodal Approach to UTI Prevention

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ClinicalTrials.gov Identifier: NCT03996057
Recruitment Status : Not yet recruiting
First Posted : June 24, 2019
Last Update Posted : September 5, 2019
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:

Urinary tract infections (UTIs) are the most common bacterial infection and are especially common in postmenopausal women, who often experience recurrent UTIs. Women with recurrent UTIs are commonly treated with antibiotics, but side effects, collateral damage to commensal bacteria, and antimicrobial resistance result from frequent antibiotic use. It is paramount that researchers develop non-antibiotic treatment strategies for UTIs.

Several non-antibiotic strategies may be successful in preventing recurrent UTIs in postmenopausal women, including low-dose vaginal estrogen, d-mannose, and methenamine hippurate. Methenamine hippurate (MH) is interesting as it causes few side effects, kills bacteria by denaturing bacterial proteins, RNA, and DNA, and does not develop resistance. Several studies have demonstrated the efficacy of daily methenamine on the incidence of UTI. However, women often require multiple therapies in order to prevent recurrence. There are currently few guidelines to help clinicians identify optimal treatment regimens for non-antibiotic prevention of UTI.

The purpose of this pilot study is to examine the feasibility of developing a sequential, multiple assignment, randomization trial (SMART); and examine the treatment effect of MH in combination with vaginal estrogen (VET) and D-mannose on prevention of UTI. The investigators plan to examine the efficacy of the addition of MH to low dose VET and d-mannose in the UTI prevention through randomization to MH + VET + D-mannose vs continuing VET + D-mannose alone. The primary outcome will be the proportion of patients who have symptomatic, culture-proven UTI during a 3 month treatment period. The investigators hypothesize that women on low dose VET, d-mannose, and MH will be less likely to have recurrent UTI than those with VET and d-mannose alone.

This study uses a pragmatic, longitudinal approach that mimics patients' clinical experiences and physicians' decision points during management of UTI prophylaxis. Through this randomized, controlled pilot study, this proposal would allow the investigators to examine the feasibility of conducting a larger-scale, adaptive study trial, and estimate the treatment effect of a non-antibiotic regimen augmented with MH in women who continue to develop recurrence.


Condition or disease Intervention/treatment Phase
UTI Female Urogenital Diseases UTI - Lower Urinary Tract Infection Drug: Methenamine Hippurate 1000 MG Drug: Vaginal estrogen Dietary Supplement: D-mannose Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized control pilot trial
Masking: None (Open Label)
Masking Description: Attempt will be made to mask the current arm during assessment of outcomes (symptomatic UTI) when the participant calls in with symptoms, as the participant will be asked not to reveal their current prophylaxis regimen unless deemed medically or clinically necessary at the time.
Primary Purpose: Prevention
Official Title: The Efficacy and Effect of Methenamine Hippurate in a Non-antibiotic, Multimodal Approach to UTI Prevention
Estimated Study Start Date : October 1, 2019
Estimated Primary Completion Date : July 5, 2021
Estimated Study Completion Date : November 5, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Methenamine augmentation
2g methenamine hippurate twice daily for 90 days added to a baseline regimen of low dose vaginal estrogen (two to three times per week) and d-mannose (1000 mg twice daily)
Drug: Methenamine Hippurate 1000 MG
Discussed in arm/group description

Drug: Vaginal estrogen
Any form of low dose vaginal estrogen, whether ring, cream, tablet, or capsule. Depends on what patient is already using.

Dietary Supplement: D-mannose
Powder or tablet, depending on what patient is already using.

Active Comparator: No methenamine augmentation
Baseline regimen of low dose vaginal estrogen (two to three times per week) and d-mannose (1000 mg twice daily)
Drug: Vaginal estrogen
Any form of low dose vaginal estrogen, whether ring, cream, tablet, or capsule. Depends on what patient is already using.

Dietary Supplement: D-mannose
Powder or tablet, depending on what patient is already using.




Primary Outcome Measures :
  1. Culture proven, symptomatic urinary tract infection (UTI) [ Time Frame: 3 months ]
    Proportion of patients who have symptomatic, culture-proven UTI during a 3 month treatment period.

  2. Recruitment rate [ Time Frame: Through study recruitment, an average of 1 year ]
    Proportion of patients approached who are eligible for the study and consent to participate vs those who do not agree to participate.

  3. Retention rate [ Time Frame: 3 months ]
    Proportion of patients who finish the 3 months study versus those who are recruited, randomized, but do not complete the study.

  4. Adherence [ Time Frame: 3 months ]
    Average adherence to recommended dosage/frequency of vaginal estrogen, d-mannose, and methenamine hippurate use, as well as achievement of at least 75% adherence to medications.


Secondary Outcome Measures :
  1. Frequency of culture proven, symptomatic urinary tract infection (UTI) [ Time Frame: 3 months ]
    Average number of symptomatic, culture-proven UTI during a 3 month treatment period.

  2. Treatment for urinary tract infection (UTI) [ Time Frame: 3 months ]
    Proportion of patients who report treatment for symptomatic UTI during a 3 month treatment period. This may be culture-proven or not.

  3. Side effects or adverse events [ Time Frame: 3 months ]
    We will describe side effects that occur during prophylaxis with vaginal estrogen + d-mannose, with or without methenamine hippurate.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Postmenopausal women
  • History of recurrent UTI (>=3 culture proven UTIs in one year or >=2 in 6 months)
  • Recurrent, culture proven UTI while on vaginal estrogen for at least 4 weeks + d-mannose prophylaxis
  • English speaker

Exclusion Criteria:

  • Not postmenopausal
  • Complicated UTIs
  • Known renal tract anomaly
  • Liver dysfunction
  • Neurogenic bladder
  • Incomplete bladder emptying (PVR > 150 cc when voided volume >150 cc)
  • Self-catheterization or use of indwelling catheter
  • Contraindication to vaginal estrogen, methenamine hippurate, or d-mannose, including allergic reactions
  • History of or current endometrial cancer
  • History of estrogen sensitive breast cancer without approval of patient, patient's oncologist, oncologic surgeon, or primary care physician to use vaginal estrogen after counseling
  • History of interstitial cystitis/painful bladder syndrome
  • Urothelial cancer
  • Enrolled in other clinical trials for UTIs other than Washington University study IRB# 201711120
  • Currently on daily antibiotic prophylaxis and unwilling to stop this intervention

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03996057


Contacts
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Contact: Zoe Jennings, BS 3147475174 zoejennings@email.wustl.edu
Contact: Christine Chu, MD 3147471402 cchu23@wustl.edu

Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Christine Chu, MD Washington University School of Medicine

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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03996057     History of Changes
Other Study ID Numbers: 201804086
First Posted: June 24, 2019    Key Record Dates
Last Update Posted: September 5, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Washington University School of Medicine:
Urinary tract infection
UTI
Women
Postmenopausal women
Prevention
Non-antibiotic
Additional relevant MeSH terms:
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Estrogens
Urinary Tract Infections
Infection
Urologic Diseases
Methenamine
Methenamine hippurate
Methenamine mandelate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Anti-Bacterial Agents