<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/NCT04477837</url>
  </required_header>
  <id_info>
    <org_study_id>HEMBLED</org_study_id>
    <nct_id>NCT04477837</nct_id>
  </id_info>
  <brief_title>Prospective Comparison of Incidence of Heavy Menstrual Bleeding in Women Treated With Direct Oral Anticoagulants</brief_title>
  <official_title>Prospective, Observational, Non-interventional Open-label Multicenter Registry Regarding the Incidence of Heavy Menstrual Bleeding in Women of Reproductive Age Treated With Direct Oral Anticoagulants Because of Venous Thromboembolism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardioangiologisches Centrum Bethanien</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cardioangiologisches Centrum Bethanien</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prospective comparison of the incidence of heavy menstrual bleeding (HMB) in women of&#xD;
      reproductive age treated with direct oral anticoagulants (DOACs)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be treated as standard of care, no randomization schedule, no blinded&#xD;
      investigational product (IP).&#xD;
&#xD;
      The decision which DOAC will be given is made before the subject will enter the trial. The&#xD;
      DOAC has to be taken at least for seven days.&#xD;
&#xD;
      The registry is non-interventional (NIS) with routine blood draw at baseline and at month 4&#xD;
      after inclusion. The prospective follow up will be up to four months. Three consecutive&#xD;
      menstrual bleeding cycles will be documented by the participating patients at home. One&#xD;
      baseline data reporting and one follow up reporting after four months are planned in the&#xD;
      participating coagulation centers.&#xD;
&#xD;
      The primary aim is the comparison of the frequency of heavy menstrual bleeding in female&#xD;
      patients of reproductive age anticoagulated with DOACs using a modified pictorial blood loss&#xD;
      assessment chart.&#xD;
&#xD;
      Secondary aims are the prevalence of von Willebrand disease in young anticoagulated female&#xD;
      patients and correlation of HMB with age, International Society of Thrombosis and Hemostasis&#xD;
      bleeding assessment tool at inclusion, Blood group, anatomical reasons i.e. underlying&#xD;
      uterine pathologies, i. e. presence of uterine fibroids, endometrial polyps and/or&#xD;
      adenomyosis, occurrence of iron deficiency, hemoglobin level and intermittent use of&#xD;
      non-steroidal anti-inflammatory drug (NSAID).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 15, 2020</start_date>
  <completion_date type="Anticipated">June 15, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>4 Months</target_duration>
  <primary_outcome>
    <measure>Primary observation point (for all patients)</measure>
    <time_frame>baseline and monthly up to month 4</time_frame>
    <description>Frequency of heavy menstrual bleeding in anticoagulated female patients of reproductive Age using a modified Pictorial blood loss assessment Chart (PBAC)-Score (Higham, Br J Obstet Gynaecol 1990; 97: 734-9)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary observation points (for all patients)</measure>
    <time_frame>up to 16 weeks</time_frame>
    <description>Correlation of heavy menstrual bleeding with von Willebrand's disease; Age; ISTH-BAT-Score at inclusion; blood Group; anatomical reasons i.e. underlying uterine pathologies, i.e. presence of uterine fibroids, endometrial polyps and/or adenomyosis; iron deficiency; hemoglobin level; intermittent use of NSAR</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Heavy Menstrual Bleeding</condition>
  <arm_group>
    <arm_group_label>direct oral anticoagulant (DOAC) No.1</arm_group_label>
    <description>Apixaban 5mg, oral, twice daily for at least four months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>direct oral anticoagulant (DOAC) No.2</arm_group_label>
    <description>Rivaroxaban 20mg, oral, once daily for at least four months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>direct oral anticoagulant (DOAC) No.3</arm_group_label>
    <description>Edoxaban 60mg, oral, once daily for at least four months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>direct oral anticoagulant (DOAC) No.4</arm_group_label>
    <description>Dabigatran 150mg, oral, twice daily for at least four months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban 5 MG</intervention_name>
    <description>frequency of heavy menstrual bleeding</description>
    <arm_group_label>direct oral anticoagulant (DOAC) No.1</arm_group_label>
    <other_name>Eliquis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivaroxaban 20 MG</intervention_name>
    <description>frequency of heavy menstrual bleeding</description>
    <arm_group_label>direct oral anticoagulant (DOAC) No.2</arm_group_label>
    <other_name>Xarelto</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Edoxaban 60 MG</intervention_name>
    <description>frequency of heavy menstrual bleeding</description>
    <arm_group_label>direct oral anticoagulant (DOAC) No.3</arm_group_label>
    <other_name>Lixiana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabigatran 150 Mg Oral Capsule</intervention_name>
    <description>frequency of heavy menstrual bleeding</description>
    <arm_group_label>direct oral anticoagulant (DOAC) No.4</arm_group_label>
    <other_name>Pradaxa</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Expected number of patients estimated by study duration n=150 patients treated with direct&#xD;
        oral anticoagulants (DOAC) due to venous thromboembolism.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women with venous thromboembolism&#xD;
&#xD;
          -  Age: 18 - 50 years&#xD;
&#xD;
          -  Regular menstrual bleeding&#xD;
&#xD;
          -  Treatment with DOACs for at least 7 days before inclusion&#xD;
&#xD;
          -  Full therapeutic anticoagulation with rivaroxaban 1 x 20 mg, apixaban 2 x 5 mg,&#xD;
             edoxaban 60mg once daily or dabigatran 2 x 150mg for at least the next four months&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hysterectomy or ovariectomy&#xD;
&#xD;
          -  Known heavy menstrual bleeding&#xD;
&#xD;
          -  Hormonal contraceptives&#xD;
&#xD;
          -  Hormone replacement therapy&#xD;
&#xD;
          -  Use of hormone releasing intrauterine System (IUS)&#xD;
&#xD;
          -  Contraindications to treatment with DOACs&#xD;
&#xD;
          -  Treatment with rivaroxaban 15 mg twice daily (first three weeks after diagnosis of&#xD;
             venous thrombosis) or apixaban 10 mg twice daily (first week after diagnosis of venous&#xD;
             thrombosis)&#xD;
&#xD;
          -  Treatment with rivaroxaban (10 mg or 15 mg once daily) or apixaban (2,5 mg twice&#xD;
             daily) in reduced therapeutic dosages&#xD;
&#xD;
          -  Participation in any other trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edelgard Lindhoff-Last, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cardioangiologisches Zentrum Bethanien</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Edelgard Lindhoff-Last, Prof.</last_name>
    <phone>+49-699450280</phone>
    <email>e.lindhoff-last@ccb.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cardioangiology Center Bethanien (CCB)</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>60389</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edelgard Lindhoff-Last, Prof.MD</last_name>
      <phone>+49 69 9450280</phone>
      <email>e.lindhoff-last@ccb.de</email>
    </contact>
    <investigator>
      <last_name>Edelgard Lindhoff-Last, Prof</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cardioangiologisches Centrum Bethanien</investigator_affiliation>
    <investigator_full_name>Prof. Dr. med. E. Lindhoff-Last</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Menorrhagia</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rivaroxaban</mesh_term>
    <mesh_term>Apixaban</mesh_term>
    <mesh_term>Edoxaban</mesh_term>
    <mesh_term>Dabigatran</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04477837
org study id: HEMBLED
nct id: NCT04477837
lead sponsor: 
has dmc: Yes
is fda regulated device: No
Prospective comparison of the incidence of heavy menstrual bleeding (HMB) in women of
      reproductive age treated with direct oral anticoagulants (DOACs)
Patients will be treated as standard of care, no randomization schedule, no blinded
      investigational product (IP).

      The decision which DOAC will be given is made before the subject will enter the trial. The
      DOAC has to be taken at least for seven days.

      The registry is non-interventional (NIS) with routine blood draw at baseline and at month 4
      after inclusion. The prospective follow up will be up to four months. Three consecutive
      menstrual bleeding cycles will be documented by the participating patients at home. One
      baseline data reporting and one follow up reporting after four months are planned in the
      participating coagulation centers.

      The primary aim is the comparison of the frequency of heavy menstrual bleeding in female
      patients of reproductive age anticoagulated with DOACs using a modified pictorial blood loss
      assessment chart.

      Secondary aims are the prevalence of von Willebrand disease in young anticoagulated female
      patients and correlation of HMB with age, International Society of Thrombosis and Hemostasis
      bleeding assessment tool at inclusion, Blood group, anatomical reasons i.e. underlying
      uterine pathologies, i. e. presence of uterine fibroids, endometrial polyps and/or
      adenomyosis, occurrence of iron deficiency, hemoglobin level and intermittent use of
      non-steroidal anti-inflammatory drug (NSAID).
observational model: Cohort
time perspective: Prospective
measure: Primary observation point (for all patients)
time frame: baseline and monthly up to month 4
description: Frequency of heavy menstrual bleeding in anticoagulated female patients of reproductive Age using a modified Pictorial blood loss assessment Chart (PBAC)-Score (Higham, Br J Obstet Gynaecol 1990; 97: 734-9)
measure: Secondary observation points (for all patients)
time frame: up to 16 weeks
description: Correlation of heavy menstrual bleeding with von Willebrand's disease; Age; ISTH-BAT-Score at inclusion; blood Group; anatomical reasons i.e. underlying uterine pathologies, i.e. presence of uterine fibroids, endometrial polyps and/or adenomyosis; iron deficiency; hemoglobin level; intermittent use of NSAR
arm group label: direct oral anticoagulant (DOAC) No.1
description: Apixaban 5mg, oral, twice daily for at least four months
arm group label: direct oral anticoagulant (DOAC) No.2
description: Rivaroxaban 20mg, oral, once daily for at least four months
arm group label: direct oral anticoagulant (DOAC) No.3
description: Edoxaban 60mg, oral, once daily for at least four months
arm group label: direct oral anticoagulant (DOAC) No.4
description: Dabigatran 150mg, oral, twice daily for at least four months
intervention type: Drug
intervention name: Apixaban 5 MG
description: frequency of heavy menstrual bleeding
arm group label: direct oral anticoagulant (DOAC) No.1
other name: Eliquis
intervention type: Drug
intervention name: Rivaroxaban 20 MG
description: frequency of heavy menstrual bleeding
arm group label: direct oral anticoagulant (DOAC) No.2
other name: Xarelto
intervention type: Drug
intervention name: Edoxaban 60 MG
description: frequency of heavy menstrual bleeding
arm group label: direct oral anticoagulant (DOAC) No.3
other name: Lixiana
intervention type: Drug
intervention name: Dabigatran 150 Mg Oral Capsule
description: frequency of heavy menstrual bleeding
arm group label: direct oral anticoagulant (DOAC) No.4
other name: Pradaxa
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Edelgard Lindhoff-Last, Prof.
role: Principal Investigator
affiliation: Cardioangiologisches Zentrum Bethanien
last name: Edelgard Lindhoff-Last, Prof.
phone: +49-699450280
email: e.lindhoff-last@ccb.de
facility: 
status: Recruiting
contact: 
investigator: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Cardioangiologisches Centrum Bethanien
investigator full name: Prof. Dr. med. E. Lindhoff-Last
investigator title: Clinical Professor
mesh term: Menorrhagia
mesh term: Hemorrhage
mesh term: Rivaroxaban
mesh term: Apixaban
mesh term: Edoxaban
mesh term: Dabigatran
sharing ipd: No