<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/NCT03779633</url>
  </required_header>
  <id_info>
    <org_study_id>EstrogenPOP</org_study_id>
    <nct_id>NCT03779633</nct_id>
  </id_info>
  <brief_title>Preoperative Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse</brief_title>
  <official_title>Preoperative Locally Applied Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse: Changes in Subjective and Objective Outcome - a Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction With increasing age the incidence of pelvic organ prolapse (POP) rises and will&#xD;
      increase substantially in the future according to forecasting studies. It is possible that&#xD;
      oestrogens, alone or in combination with other forms of therapy, may assist in the management&#xD;
      of POP by increasing collagen synthesis and thereby improving the strength of the weakened&#xD;
      vaginal epithelium. Yet, studies investigating the effect of topical oestrogen and its impact&#xD;
      on POP associated symptoms, both self-reported improvement and observations of objective&#xD;
      improvement, are lacking.&#xD;
&#xD;
      Objective To evaluate the subjective efficacy concerning prolapse associated complaints&#xD;
      measured by the German pelvic floor questionnaire (domain POP: POP-score) after preoperative&#xD;
      use of local oestrogen compared to preoperative placebo treatment in postmenopausal women&#xD;
      with symptomatic pelvic organ prolapse. Further variables of interest are POP-score after 3&#xD;
      months, differences regarding the objective prolapse quantification system (POP-Q), surgical&#xD;
      outcome and tissue operability assessed by the surgeon.&#xD;
&#xD;
      Methods In this prospective, randomized, double-blind, placebo-controlled, multicenter study&#xD;
      the investigators aim to include 120 postmenopausal women with symptomatic pelvic organ&#xD;
      prolapse and indicated operative procedure. An analysis of covariance will be computed with&#xD;
      the depending variable POP-score after 6 weeks and the independent variables group (verum&#xD;
      versus placebo) and Pop-Score at baseline.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2, 2017</start_date>
  <completion_date type="Actual">August 27, 2020</completion_date>
  <primary_completion_date type="Actual">August 27, 2020</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>
    <intervention_model_description>Double-blind, Placebo-controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>subjective prolapse associated symptoms (measured with the validated German pelvic floor questionnaire)</measure>
    <time_frame>change from baseline POP Score at 6 weeks after treatment</time_frame>
    <description>treatment efficacy of preoperative vaginally administered oestrogen in postmenopausal women with symptomatic pelvic organ prolapse in comparison to placebo, measured by a subjective questionnaire. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>operative time in minutes</measure>
    <time_frame>up to 1 week postoperative</time_frame>
    <description>effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of stay in days</measure>
    <time_frame>up to 1 week postoperative</time_frame>
    <description>effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>intraoperative blood loss in ml</measure>
    <time_frame>up to 1 week postoperative</time_frame>
    <description>effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>blood circulation of the tissue (good, regular, scarce, no blood circulation)</measure>
    <time_frame>on day of surgery</time_frame>
    <description>differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>separability of the tissue layers (good, regular, scarce, not possible)</measure>
    <time_frame>on day of surgery</time_frame>
    <description>differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>easy separation from the bladder (yes/no)</measure>
    <time_frame>on day of surgery</time_frame>
    <description>differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>easy opening of the Douglas cavity (Yes/no)</measure>
    <time_frame>on day of surgery</time_frame>
    <description>differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>subjective (all domains of the pelvic floor questionnaire) outcome 3 months postoperative</measure>
    <time_frame>3 months postoperative</time_frame>
    <description>possible differences regarding subjective outcome parameters between intervention and placebo-group 3 months after operation. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>objective (POP-Q score) outcome 3 months postoperative</measure>
    <time_frame>3 months postoperative</time_frame>
    <description>possible differences regarding objective outcome parameters between intervention and placebo-group 3 months after operation. POP-Q Score (Score between 0 and 4). The POP- quantification system consists of six defined points of measurement (Aa, Ba, C,D,Ap,Bp) and three other landmarks (GH,TVL, PB). Each is measured in centimeters above the hymen (negative number) or below the hymen (positive number).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Pelvic Organ Prolapse</condition>
  <arm_group>
    <arm_group_label>Linoladiol Estradiol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Linoladiol Estradiol cream 6 weeks before surgery of pelvic organ prolapse</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo cream 6 weeks before surgery of pelvic organ prolapse</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Linoladiol Estradiol</intervention_name>
    <description>Linoladiol Estradiol Initial dose (week 1): 1 application (2g Linoladiol = 0.2mg Estradiol) every day for the first week Maintenance dose 1 (week 2) : 1 application (2g Linoladiol = 0.2mg Estradiol) every 48 hours the following week.&#xD;
Maintenance dose 2 (week 3-6): 1 application (2g Linoladiol = 0.2mg Estradiol) twice per week the following 4 weeks.&#xD;
Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks</description>
    <arm_group_label>Linoladiol Estradiol</arm_group_label>
    <other_name>Montavit ATC Code G03CA03</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo vaginal cream</intervention_name>
    <description>Initial dose (week 1): 1 application every day for the first week Maintenance dose 1 (week 2) : 1 application every 48 hours the following week.&#xD;
Maintenance dose 2 (week 3-6): 1 application twice per week the following 4 weeks.&#xD;
Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenopausal women&#xD;
&#xD;
          -  Able to read, understand and sign informed consent&#xD;
&#xD;
          -  Able to apply a vaginal cream&#xD;
&#xD;
          -  Symptomatic pelvic organ prolapse with planned and indicated prolapse surgical repair&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Suspicion or history of breast cancer or other oestrogen responsive malignancies&#xD;
             (endometrial cancer)&#xD;
&#xD;
          -  unexplained abnormal vaginal bleeding&#xD;
&#xD;
          -  history of deep vein thrombosis&#xD;
&#xD;
          -  inherited or acquired blood clotting disorders (eg, APC resistance, Antithrombin III&#xD;
             deficiency)&#xD;
&#xD;
          -  transient ischaemic attack, myo- cardial infarction or ischaemic heart disease&#xD;
&#xD;
          -  Hypersensitivity to oestrogen&#xD;
&#xD;
          -  Unable to read and sign informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Obstetrics and Gynecology, University of Tulln</name>
      <address>
        <city>Tulln</city>
        <zip>3430</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of General Gynecology and Gynecologic Oncology of the Medical University Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <reference>
    <citation>Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for Pelvic Floor Disorders: A Systematic Review. PLoS One. 2015 Sep 18;10(9):e0136265. doi: 10.1371/journal.pone.0136265. eCollection 2015.</citation>
    <PMID>26383760</PMID>
  </reference>
  <reference>
    <citation>Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab. 2014 Oct;99(10):3728-36. doi: 10.1210/jc.2014-1216. Epub 2014 Jun 20.</citation>
    <PMID>24947034</PMID>
  </reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>July 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 16, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>November 16, 2020</last_update_submitted>
  <last_update_submitted_qc>November 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Barbara Bodner-Adler</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Local Oestrogen</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prolapse</mesh_term>
    <mesh_term>Pelvic Organ Prolapse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 2, 2021</submitted>
    <returned>September 30, 2021</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03779633
org study id: EstrogenPOP
nct id: NCT03779633
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Introduction With increasing age the incidence of pelvic organ prolapse (POP) rises and will
      increase substantially in the future according to forecasting studies. It is possible that
      oestrogens, alone or in combination with other forms of therapy, may assist in the management
      of POP by increasing collagen synthesis and thereby improving the strength of the weakened
      vaginal epithelium. Yet, studies investigating the effect of topical oestrogen and its impact
      on POP associated symptoms, both self-reported improvement and observations of objective
      improvement, are lacking.

      Objective To evaluate the subjective efficacy concerning prolapse associated complaints
      measured by the German pelvic floor questionnaire (domain POP: POP-score) after preoperative
      use of local oestrogen compared to preoperative placebo treatment in postmenopausal women
      with symptomatic pelvic organ prolapse. Further variables of interest are POP-score after 3
      months, differences regarding the objective prolapse quantification system (POP-Q), surgical
      outcome and tissue operability assessed by the surgeon.

      Methods In this prospective, randomized, double-blind, placebo-controlled, multicenter study
      the investigators aim to include 120 postmenopausal women with symptomatic pelvic organ
      prolapse and indicated operative procedure. An analysis of covariance will be computed with
      the depending variable POP-score after 6 weeks and the independent variables group (verum
      versus placebo) and Pop-Score at baseline.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double-blind, Placebo-controlled
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: subjective prolapse associated symptoms (measured with the validated German pelvic floor questionnaire)
time frame: change from baseline POP Score at 6 weeks after treatment
description: treatment efficacy of preoperative vaginally administered oestrogen in postmenopausal women with symptomatic pelvic organ prolapse in comparison to placebo, measured by a subjective questionnaire. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome
measure: operative time in minutes
time frame: up to 1 week postoperative
description: effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo
measure: length of stay in days
time frame: up to 1 week postoperative
description: effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo
measure: intraoperative blood loss in ml
time frame: up to 1 week postoperative
description: effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo
measure: blood circulation of the tissue (good, regular, scarce, no blood circulation)
time frame: on day of surgery
description: differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation
measure: separability of the tissue layers (good, regular, scarce, not possible)
time frame: on day of surgery
description: differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation
measure: easy separation from the bladder (yes/no)
time frame: on day of surgery
description: differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation
measure: easy opening of the Douglas cavity (Yes/no)
time frame: on day of surgery
description: differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation
measure: subjective (all domains of the pelvic floor questionnaire) outcome 3 months postoperative
time frame: 3 months postoperative
description: possible differences regarding subjective outcome parameters between intervention and placebo-group 3 months after operation. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome.
measure: objective (POP-Q score) outcome 3 months postoperative
time frame: 3 months postoperative
description: possible differences regarding objective outcome parameters between intervention and placebo-group 3 months after operation. POP-Q Score (Score between 0 and 4). The POP- quantification system consists of six defined points of measurement (Aa, Ba, C,D,Ap,Bp) and three other landmarks (GH,TVL, PB). Each is measured in centimeters above the hymen (negative number) or below the hymen (positive number).
arm group label: Linoladiol Estradiol
arm group type: Experimental
description: Linoladiol Estradiol cream 6 weeks before surgery of pelvic organ prolapse
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo cream 6 weeks before surgery of pelvic organ prolapse
intervention type: Drug
intervention name: Linoladiol Estradiol
description: Linoladiol Estradiol Initial dose (week 1): 1 application (2g Linoladiol = 0.2mg Estradiol) every day for the first week Maintenance dose 1 (week 2) : 1 application (2g Linoladiol = 0.2mg Estradiol) every 48 hours the following week.
Maintenance dose 2 (week 3-6): 1 application (2g Linoladiol = 0.2mg Estradiol) twice per week the following 4 weeks.
Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks
arm group label: Linoladiol Estradiol
other name: Montavit ATC Code G03CA03
intervention type: Other
intervention name: Placebo vaginal cream
description: Initial dose (week 1): 1 application every day for the first week Maintenance dose 1 (week 2) : 1 application every 48 hours the following week.
Maintenance dose 2 (week 3-6): 1 application twice per week the following 4 weeks.
Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Austria
citation: Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for Pelvic Floor Disorders: A Systematic Review. PLoS One. 2015 Sep 18;10(9):e0136265. doi: 10.1371/journal.pone.0136265. eCollection 2015.
PMID: 26383760
citation: Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab. 2014 Oct;99(10):3728-36. doi: 10.1210/jc.2014-1216. Epub 2014 Jun 20.
PMID: 24947034
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Barbara Bodner-Adler
investigator title: Clinical Professor
mesh term: Prolapse
mesh term: Pelvic Organ Prolapse
mesh term: Estradiol
sharing ipd: Undecided
submitted: September 2, 2021
returned: September 30, 2021