Microscopic HematuriaPhase 4EVERNCT02213757
Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH)
A Phase 4 study testing Premarin vaginal estrogen cream in people with Microscopic Hematuria, run by Medstar Health Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to determine if vaginal estrogen use is associated with resolution of blood in the urine (microscopic hematuria) in postmenopausal women. The hypothesis is that postmenopausal women with blood in the urine (microscopic hematuria) will have higher rates of resolution of hematuria after… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Microscopic Hematuria
- What is being tested?
- Premarin vaginal estrogen cream
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Post-menopausal women
- Asymptomatic microscopic hematuria (three or more red blood cells per high powered field on a single urine microscopy) in the absence of urinary tract infection.
Who cannot join
- Known urologic disease
- Presence of gross hematuria
- Presence of indwelling urologic foreign body (foley catheter, ureteral stent)
- Inability to obtain intravenous contrast CT scan (elevated creatinine, severe contrast allergy)
- History of pelvic irradiation or malignancy
- Not a candidate for vaginal estrogen
Show all 10Show fewer
- Allergy to vaginal estrogen
- Current or prior diagnosis of breast or endometrial cancer
- History of deep vein thrombosis/pulmonary embolus
- Hypercoagulable state
Trial locations and contacts
1 site in 1 country.
United States1 site
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20001
About this study
Official title: Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH): A Randomized Controlled Trial [EVER Study]
The purpose of this study is to determine if vaginal estrogen use is associated with resolution of blood in the urine (microscopic hematuria) in postmenopausal women. The hypothesis is that postmenopausal women with blood in the urine (microscopic hematuria) will have higher rates of resolution of hematuria after treatment course with vaginal conjugated equine estrogen cream compared to placebo cream
Read the detailed description
This is a randomized controlled trial of vaginal estrogen cream for postmenopausal women with microscopic hematuria (AMH). Potential subjects will be screened with a dipstick urinalysis of a catheterized urine specimen, followed by microscopic urinalysis and urine culture if urine dipstick is positive for trace blood or greater. Women who are identified as having asymptomatic microscopic hematuria (>3 red blood cells (RBC) per high powered field (hpf)) on a single urine microscopy specimen in the absence of urinary tract infection or other benign cause will be eligible for enrollment.
Women meeting inclusion criteria will be randomized to either conjugated equine estrogen cream (Premarin, 0.625mg conjugated estrogens) or placebo cream for 8 weeks. Microscopic urinalysis of a catheterized urine specimen will be re-checked at 8 weeks to check for reduction, resolution or persistence of AMH. During the 8 weeks of vaginal estrogen or placebo, women will complete the recommended AMH workup as dictated by the American Urologic Association (AUA) guidelines (cystourethroscopy, serum blood urea nitrogen and creatinine levels, and computed tomography (CT) scan of the abdomen and pelvis with and without intravenous contrast).1
Validated questionnaires to assess vaginal atrophy and symptoms of urinary urgency and frequency will be completed at time of randomization and again at 8 weeks. Cost analysis of the standard AMH workup (cystourethroscopy and CT scan) versus empiric treatment with 8 weeks of vaginal estrogen cream will be calculated based on Medicare reimbursement, as well as market price for vaginal estrogen cream Additionally, patients will be asked to complete a questionnaire to assess the level of bother associated with completing the current AMH workup of CT scan and cystoscopy as compared to completing a treatment course of vaginal estrogen cream.
Secondary analyses will determine whether there are additional benefits to a trial period of vaginal estrogen cream in postmenopausal women with AMH prior to reflexively screening for urinary tract abnormalities. We will compare the cost of a standard AMH workup to a treatment course of vaginal estrogen cream, to determine whether vaginal estrogen with potential resolution of AMH is associated with any savings prior to pursuing further workup. Additionally, questionnaires will ask study participants whether they would prefer to undergo the current AUA AMH workup or a treatment course of vaginal cream, in order to assess bother and anxiety associated with these interventions.
- Conditions
- Microscopic Hematuria
- Being tested
- Premarin vaginal estrogen cream, Placebo vaginal cream
- Keywords
- Hematuria, Menopause, Urinalysis
- Medical subject headings
- Hematuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Premarin vaginal estrogen creamDrug
Also called Conjugated estrogens vaginal cream
Placebo vaginal creamDrug
Also called Other names have not been specified
Inactive vaginal cream manufactured to mimic Premarin vaginal cream
| Study group | Role | What they receive |
|---|---|---|
| Premarin vaginal cream | Experimental | Premarin vaginal cream to be applied intra-vaginally and to vulva as follows: 1 gram nightly for 2 weeks, followed by 0.5 gram twice weekly for 6 weeks. Receives: Drug: Premarin vaginal estrogen cream |
| Placebo vaginal cream | Placebo comparator | Placebo vaginal cream to be applied intra-vaginally and to vulva as follows: 1 gram nightly for 2 weeks, followed by 0.5 gram twice weekly for 6 weeks. Receives: Drug: Placebo vaginal cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Resolution of Microscopic Hematuria
Microscopic urinalysis will be performed after an 8 week trial of vaginal estrogen or placebo. Resolution of microscopic hematuria is defined according to AUA guidelines, <3 red blood cells per high powered field.
Measured: 8 weeks
Secondary outcomes (1)
Number of Participants With Improvement in Symptoms of Urinary Frequency and Urgency
To determine the effect of vaginal estrogen compared to placebo on symptoms of urinary frequency and urgency. Participants that experience at least one point reduction in OAB-q score will qualify as a participant with improvement in these symptoms.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionDec 2015
- Study completionDec 2015
Why it stopped: Low Enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Microscopic HematuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medstar Health Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Cheryl B Iglesia, MD, Principal investigator, Medstar Health Research InstituteLee A Richter, MD, Study director, Medstar Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02213757
- Sponsor's protocol ID
- 2014-071
- Acronym
- EVER
- Status last verified
- Mar 2023
- First submitted
- 8 Aug 2014
- Last updated
- 15 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Wu JM, Williams KS, Hundley AF, Jannelli ML, Visco AG. Microscopic hematuria as a predictive factor for detecting bladder cancer at cystoscopy in women with irritative voiding symptoms. Am J Obstet Gynecol. 2006 May;194(5):1423-6. doi: 10.1016/j.ajog.2006.01.053. Epub 2006 Mar 30.
PubMed 16579943Shalom DF, Lin SN, St Louis S, Lind LR, Winkler HA. The prevalence of microscopic hematuria in women with pelvic organ prolapse. Female Pelvic Med Reconstr Surg. 2011 Nov;17(6):290-2. doi: 10.1097/SPV.0b013e3182357afb.
PubMed 22453223Jung H, Gleason JM, Loo RK, Patel HS, Slezak JM, Jacobsen SJ. Association of hematuria on microscopic urinalysis and risk of urinary tract cancer. J Urol. 2011 May;185(5):1698-703. doi: 10.1016/j.juro.2010.12.093. Epub 2011 Mar 21.
PubMed 21419446
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH): A Randomized Controlled Trial [EVER Study]
- ClinicalTrials.gov ID
- NCT02213757
- Acronym / sponsor ID
- EVER / 2014-071
- Conditions
- Microscopic Hematuria
- Keywords
- Hematuria, Menopause, Urinalysis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Enrollment
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Medstar Health Research InstituteUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Aug 2014 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 11 Aug 2014 (estimated)
- Results
- Posted 15 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if vaginal estrogen use is associated with resolution of blood in the urine (microscopic hematuria) in postmenopausal women. The hypothesis is that postmenopausal women with blood in the urine (microscopic hematuria) will have higher rates of resolution of hematuria after treatment course with vaginal conjugated equine estrogen cream compared to placebo cream
Detailed description
This is a randomized controlled trial of vaginal estrogen cream for postmenopausal women with microscopic hematuria (AMH). Potential subjects will be screened with a dipstick urinalysis of a catheterized urine specimen, followed by microscopic urinalysis and urine culture if urine dipstick is positive for trace blood or greater. Women who are identified as having asymptomatic microscopic hematuria (>3 red blood cells (RBC) per high powered field (hpf)) on a single urine microscopy specimen in the absence of urinary tract infection or other benign cause will be eligible for enrollment.
Women meeting inclusion criteria will be randomized to either conjugated equine estrogen cream (Premarin, 0.625mg conjugated estrogens) or placebo cream for 8 weeks. Microscopic urinalysis of a catheterized urine specimen will be re-checked at 8 weeks to check for reduction, resolution or persistence of AMH. During the 8 weeks of vaginal estrogen or placebo, women will complete the recommended AMH workup as dictated by the American Urologic Association (AUA) guidelines (cystourethroscopy, serum blood urea nitrogen and creatinine levels, and computed tomography (CT) scan of the abdomen and pelvis with and without intravenous contrast).1
Validated questionnaires to assess vaginal atrophy and symptoms of urinary urgency and frequency will be completed at time of randomization and again at 8 weeks. Cost analysis of the standard AMH workup (cystourethroscopy and CT scan) versus empiric treatment with 8 weeks of vaginal estrogen cream will be calculated based on Medicare reimbursement, as well as market price for vaginal estrogen cream Additionally, patients will be asked to complete a questionnaire to assess the level of bother associated with completing the current AMH workup of CT scan and cystoscopy as compared to completing a treatment course of vaginal estrogen cream.
Secondary analyses will determine whether there are additional benefits to a trial period of vaginal estrogen cream in postmenopausal women with AMH prior to reflexively screening for urinary tract abnormalities. We will compare the cost of a standard AMH workup to a treatment course of vaginal estrogen cream, to determine whether vaginal estrogen with potential resolution of AMH is associated with any savings prior to pursuing further workup. Additionally, questionnaires will ask study participants whether they would prefer to undergo the current AUA AMH workup or a treatment course of vaginal cream, in order to assess bother and anxiety associated with these interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Premarin vaginal cream | Experimental | Drug: Premarin vaginal estrogen creamPremarin vaginal cream to be applied intra-vaginally and to vulva as follows: 1 gram nightly for 2 weeks, followed by 0.5 gram twice weekly for 6 weeks. |
| Placebo vaginal cream | Placebo comparator | Drug: Placebo vaginal creamPlacebo vaginal cream to be applied intra-vaginally and to vulva as follows: 1 gram nightly for 2 weeks, followed by 0.5 gram twice weekly for 6 weeks. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Post-menopausal women
- Asymptomatic microscopic hematuria (three or more red blood cells per high powered field on a single urine microscopy) in the absence of urinary tract infection.
Key exclusion criteria (10 listed)
- Known urologic disease
- Presence of gross hematuria
- Presence of indwelling urologic foreign body (foley catheter, ureteral stent)
- Inability to obtain intravenous contrast CT scan (elevated creatinine, severe contrast allergy)
- History of pelvic irradiation or malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Premarin vaginal estrogen creamAlso: Conjugated estrogens vaginal cream | Drug | Premarin vaginal cream |
| Placebo vaginal creamAlso: Other names have not been specifiedInactive vaginal cream manufactured to mimic Premarin vaginal cream | Drug | Placebo vaginal cream |
Primary outcome
Number of Participants With Resolution of Microscopic Hematuria
Time frame: 8 weeks
Microscopic urinalysis will be performed after an 8 week trial of vaginal estrogen or placebo. Resolution of microscopic hematuria is defined according to AUA guidelines, <3 red blood cells per high powered field.
1 secondary outcome
Number of Participants With Improvement in Symptoms of Urinary Frequency and Urgency
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16579943Wu JM, Williams KS, Hundley AF, Jannelli ML, Visco AG. Microscopic hematuria as a predictive factor for detecting bladder cancer at cystoscopy in women with irritative voiding symptoms. Am J Obstet Gynecol. 2006 May;194(5):1423-6. doi: 10.1016/j.ajog.2006.01.053. Epub 2006 Mar 30.
- Background: PubMed 22453223Shalom DF, Lin SN, St Louis S, Lind LR, Winkler HA. The prevalence of microscopic hematuria in women with pelvic organ prolapse. Female Pelvic Med Reconstr Surg. 2011 Nov;17(6):290-2. doi: 10.1097/SPV.0b013e3182357afb.
- Background: PubMed 21419446Jung H, Gleason JM, Loo RK, Patel HS, Slezak JM, Jacobsen SJ. Association of hematuria on microscopic urinalysis and risk of urinary tract cancer. J Urol. 2011 May;185(5):1698-703. doi: 10.1016/j.juro.2010.12.093. Epub 2011 Mar 21.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cheryl B Iglesia, MD principal investigator
Medstar Health Research Institute
Lee A Richter, MD study director
Medstar Health Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Premarin vaginal estrogen cream in people with Microscopic Hematuria, run by Medstar Health Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Resolution of Microscopic Hematuria (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02213757, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2023.