Clinical trial NCT02213757: Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH)
Official title: Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH): A Randomized Controlled Trial [EVER Study]
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Microscopic Hematuria
Keywords: Hematuria
Menopause
Urinalysis
Lead sponsor: Medstar Health Research Institute
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2014-08-11
Enrollment: 29
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

  * Allergy to vaginal estrogen
  * Current or prior diagnosis of breast or endometrial cancer
  * History of deep vein thrombosis/pulmonary embolus
  * Hypercoagulable state

Primary outcomes:
measure: Number of Participants With Resolution of Microscopic Hematuria
timeFrame: 8 weeks
Secondary outcomes:
measure: Number of Participants With Improvement in Symptoms of Urinary Frequency and Urgency
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
Study officials:
affiliation: Medstar Health Research Institute
name: Cheryl B Iglesia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medstar Health Research Institute
name: Lee A Richter, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Shalom 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.
citation: Jung 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.