<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02213757</url>
  </required_header>
  <id_info>
    <org_study_id>2014-071</org_study_id>
    <nct_id>NCT02213757</nct_id>
  </id_info>
  <brief_title>Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH)</brief_title>
  <acronym>EVER</acronym>
  <official_title>Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH): A Randomized Controlled Trial [EVER Study]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medstar Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medstar Health Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if vaginal estrogen use is associated with&#xD;
      resolution of blood in the urine (microscopic hematuria) in postmenopausal women. The&#xD;
      hypothesis is that postmenopausal women with blood in the urine (microscopic hematuria) will&#xD;
      have higher rates of resolution of hematuria after treatment course with vaginal conjugated&#xD;
      equine estrogen cream compared to placebo cream&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized controlled trial of vaginal estrogen cream for postmenopausal women with&#xD;
      microscopic hematuria (AMH). Potential subjects will be screened with a dipstick urinalysis&#xD;
      of a catheterized urine specimen, followed by microscopic urinalysis and urine culture if&#xD;
      urine dipstick is positive for trace blood or greater. Women who are identified as having&#xD;
      asymptomatic microscopic hematuria (&gt;3 red blood cells (RBC) per high powered field (hpf)) on&#xD;
      a single urine microscopy specimen in the absence of urinary tract infection or other benign&#xD;
      cause will be eligible for enrollment.&#xD;
&#xD;
      Women meeting inclusion criteria will be randomized to either conjugated equine estrogen&#xD;
      cream (Premarin, 0.625mg conjugated estrogens) or placebo cream for 8 weeks. Microscopic&#xD;
      urinalysis of a catheterized urine specimen will be re-checked at 8 weeks to check for&#xD;
      reduction, resolution or persistence of AMH. During the 8 weeks of vaginal estrogen or&#xD;
      placebo, women will complete the recommended AMH workup as dictated by the American Urologic&#xD;
      Association (AUA) guidelines (cystourethroscopy, serum blood urea nitrogen and creatinine&#xD;
      levels, and computed tomography (CT) scan of the abdomen and pelvis with and without&#xD;
      intravenous contrast).1&#xD;
&#xD;
      Validated questionnaires to assess vaginal atrophy and symptoms of urinary urgency and&#xD;
      frequency will be completed at time of randomization and again at 8 weeks. Cost analysis of&#xD;
      the standard AMH workup (cystourethroscopy and CT scan) versus empiric treatment with 8 weeks&#xD;
      of vaginal estrogen cream will be calculated based on Medicare reimbursement, as well as&#xD;
      market price for vaginal estrogen cream Additionally, patients will be asked to complete a&#xD;
      questionnaire to assess the level of bother associated with completing the current AMH workup&#xD;
      of CT scan and cystoscopy as compared to completing a treatment course of vaginal estrogen&#xD;
      cream.&#xD;
&#xD;
      Secondary analyses will determine whether there are additional benefits to a trial period of&#xD;
      vaginal estrogen cream in postmenopausal women with AMH prior to reflexively screening for&#xD;
      urinary tract abnormalities. We will compare the cost of a standard AMH workup to a treatment&#xD;
      course of vaginal estrogen cream, to determine whether vaginal estrogen with potential&#xD;
      resolution of AMH is associated with any savings prior to pursuing further workup.&#xD;
      Additionally, questionnaires will ask study participants whether they would prefer to undergo&#xD;
      the current AUA AMH workup or a treatment course of vaginal cream, in order to assess bother&#xD;
      and anxiety associated with these interventions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low Enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Resolution of Microscopic Hematuria</measure>
    <time_frame>8 weeks</time_frame>
    <description>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, &lt;3 red blood cells per high powered field.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Improvement in Symptoms of Urinary Frequency and Urgency</measure>
    <time_frame>8 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Microscopic Hematuria</condition>
  <arm_group>
    <arm_group_label>Premarin vaginal cream</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo vaginal cream</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Premarin vaginal estrogen cream</intervention_name>
    <arm_group_label>Premarin vaginal cream</arm_group_label>
    <other_name>Conjugated estrogens vaginal cream</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo vaginal cream</intervention_name>
    <description>Inactive vaginal cream manufactured to mimic Premarin vaginal cream</description>
    <arm_group_label>Placebo vaginal cream</arm_group_label>
    <other_name>Other names have not been specified</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Post-menopausal women&#xD;
&#xD;
          -  Asymptomatic microscopic hematuria (three or more red blood cells per high powered&#xD;
             field on a single urine microscopy) in the absence of urinary tract infection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known urologic disease&#xD;
&#xD;
          -  Presence of gross hematuria&#xD;
&#xD;
          -  Presence of indwelling urologic foreign body (foley catheter, ureteral stent)&#xD;
&#xD;
          -  Inability to obtain intravenous contrast CT scan (elevated creatinine, severe contrast&#xD;
             allergy)&#xD;
&#xD;
          -  History of pelvic irradiation or malignancy&#xD;
&#xD;
          -  Not a candidate for vaginal estrogen&#xD;
&#xD;
               -  Allergy to vaginal estrogen&#xD;
&#xD;
               -  Current or prior diagnosis of breast or endometrial cancer&#xD;
&#xD;
               -  History of deep vein thrombosis/pulmonary embolus&#xD;
&#xD;
               -  Hypercoagulable state&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cheryl B Iglesia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medstar Washington Hospital Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lee A Richter, MD</last_name>
    <role>Study Director</role>
    <affiliation>Medstar Washington Hospital Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MedStar Washington Hospital Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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>
    <PMID>16579943</PMID>
  </reference>
  <reference>
    <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>
    <PMID>22453223</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21419446</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <results_first_submitted>March 1, 2022</results_first_submitted>
  <results_first_submitted_qc>March 13, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 15, 2023</results_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hematuria</keyword>
  <keyword>Menopause</keyword>
  <keyword>Urinalysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hematuria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estrogens</mesh_term>
    <mesh_term>Estrogens, Conjugated (USP)</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Premarin Vaginal Cream</title>
          <description>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.&#xD;
Premarin vaginal estrogen cream</description>
        </group>
        <group group_id="P2">
          <title>Placebo Vaginal Cream</title>
          <description>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.&#xD;
Placebo vaginal cream: Inactive vaginal cream manufactured to mimic Premarin vaginal cream</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Premarin Vaginal Cream</title>
          <description>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.&#xD;
Premarin vaginal estrogen cream</description>
        </group>
        <group group_id="B2">
          <title>Placebo Vaginal Cream</title>
          <description>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.&#xD;
Placebo vaginal cream: Inactive vaginal cream manufactured to mimic Premarin vaginal cream</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="29"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Resolution of Microscopic Hematuria</title>
        <description>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, &lt;3 red blood cells per high powered field.</description>
        <time_frame>8 weeks</time_frame>
        <population>There were 14 participants in Placebo arm, 10 completed study and 4 were lost to follow up. 6 in Placebo group had resolution of microhematuria.&#xD;
There were 15 participants in Estrogen arm, 10 completed study and 5 were lost to follow up. 10 in Estrogen group had resolution of microhematuria.</population>
        <group_list>
          <group group_id="O1">
            <title>Premarin Vaginal Cream</title>
            <description>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.&#xD;
Premarin vaginal estrogen cream</description>
          </group>
          <group group_id="O2">
            <title>Placebo Vaginal Cream</title>
            <description>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.&#xD;
Placebo vaginal cream: Inactive vaginal cream manufactured to mimic Premarin vaginal cream</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Resolution of Microscopic Hematuria</title>
          <description>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, &lt;3 red blood cells per high powered field.</description>
          <population>There were 14 participants in Placebo arm, 10 completed study and 4 were lost to follow up. 6 in Placebo group had resolution of microhematuria.&#xD;
There were 15 participants in Estrogen arm, 10 completed study and 5 were lost to follow up. 10 in Estrogen group had resolution of microhematuria.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Improvement in Symptoms of Urinary Frequency and Urgency</title>
        <description>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.</description>
        <time_frame>8 weeks</time_frame>
        <population>OAB-q scores were collected at baseline and at follow-up. Subjects with at least one point reduction in OAB-q score were recorded to show improvement in OAB-q score. Seven participants in the test group showed a reduction of at least 1 point and seven participants in the control group showed a reduction of at least 1 point.</population>
        <group_list>
          <group group_id="O1">
            <title>Premarin Vaginal Cream</title>
            <description>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.&#xD;
Premarin vaginal estrogen cream</description>
          </group>
          <group group_id="O2">
            <title>Placebo Vaginal Cream</title>
            <description>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.&#xD;
Placebo vaginal cream: Inactive vaginal cream manufactured to mimic Premarin vaginal cream</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Improvement in Symptoms of Urinary Frequency and Urgency</title>
          <description>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.</description>
          <population>OAB-q scores were collected at baseline and at follow-up. Subjects with at least one point reduction in OAB-q score were recorded to show improvement in OAB-q score. Seven participants in the test group showed a reduction of at least 1 point and seven participants in the control group showed a reduction of at least 1 point.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Premarin Vaginal Cream</title>
          <description>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.&#xD;
Premarin vaginal estrogen cream</description>
        </group>
        <group group_id="E2">
          <title>Placebo Vaginal Cream</title>
          <description>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.&#xD;
Placebo vaginal cream: Inactive vaginal cream manufactured to mimic Premarin vaginal cream</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Richter</name_or_title>
      <organization>MHRI</organization>
      <phone>2028776526</phone>
      <email>Lee.Ann.Richter@medstar.net</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02213757
org study id: 2014-071
nct id: NCT02213757
lead sponsor: 
collaborator: 
has dmc: No
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
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Number of Participants With Resolution of Microscopic Hematuria
time frame: 8 weeks
description: 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.
measure: Number of Participants With Improvement in Symptoms of Urinary Frequency and Urgency
time frame: 8 weeks
description: 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.
arm group label: Premarin vaginal cream
arm group type: Experimental
description: 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.
arm group label: Placebo vaginal cream
arm group type: Placebo Comparator
description: 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.
intervention type: Drug
intervention name: Premarin vaginal estrogen cream
arm group label: Premarin vaginal cream
other name: Conjugated estrogens vaginal cream
intervention type: Drug
intervention name: Placebo vaginal cream
description: Inactive vaginal cream manufactured to mimic Premarin vaginal cream
arm group label: Placebo vaginal cream
other name: Other names have not been specified
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Cheryl B Iglesia, MD
role: Principal Investigator
affiliation: Medstar Washington Hospital Center
last name: Lee A Richter, MD
role: Study Director
affiliation: Medstar Washington Hospital Center
facility: 
country: United States
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.
PMID: 16579943
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.
PMID: 22453223
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.
PMID: 21419446
responsible party type: Sponsor
mesh term: Hematuria
mesh term: Estrogens
mesh term: Estrogens, Conjugated (USP)
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 