<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/NCT03772366</url>
  </required_header>
  <id_info>
    <org_study_id>2018-17</org_study_id>
    <nct_id>NCT03772366</nct_id>
  </id_info>
  <brief_title>Genital Haemorrhage in Woman of Childbearing Age Treated for Venous Thromboembolism Disease : Comparison According to Oral Anticoagulant and Impact on Quality of Life</brief_title>
  <acronym>GENB-OAB</acronym>
  <official_title>Genital Haemorrhage in Woman of Childbearing Age Treated for Venous Thromboembolism Disease : Comparison According to Oral Anticoagulant and Impact on Quality of Life.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique Hopitaux De Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique Hopitaux De Marseille</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Little data are available on the genital haemorrhages in woman of childbearing age treated&#xD;
      for venous thromboembolic disease by oral anticoagulant, especially the impact on the quality&#xD;
      of life. A recent systematic review in 2016 described for the first time in patients with&#xD;
      venous thromboembolic a lower incidence in men of major haemorrhages and minor haemorrhages&#xD;
      but clinically significant compared with women (5,3% and 7,9% respectively; RR: 0,635, 95%CI&#xD;
      0,54-0,74 ; p&lt;0,001). It appears that this difference is related to genital haemorrhages and&#xD;
      some direct oral anticoagulants are more associated with hemorrhagic surge. In post-hoc&#xD;
      analyzes of phases III trials, rivaroxaban was most of the time associated with genital&#xD;
      haemorrhages compared to vitamine K antagonists, effect not found with apixaban. Four other&#xD;
      retrospective studies seem to find the same conclusions with a higher haemorrhagic risk with&#xD;
      the rivaroxaban than with vitamine K antagonist or apixaban.&#xD;
&#xD;
      However, haemorrhagic risk is defined in these studies with criteria of severity (anemia,&#xD;
      transfusion, use of a health professional, menstrual periods of more than 8 days, inter&#xD;
      mentrual bleeding, presence of blood clots) and these studies do not take into account of&#xD;
      minor haemorrhages that may affect on the quality of life and asthenia due to anemia.&#xD;
&#xD;
      Our objective is : 1- studying the proportion of women with abnormal genital haemorrhages&#xD;
      among women of childbearing age treated for venous thromboembolism disease by oral&#xD;
      anticoagulant including using a semi quantitative score of menorrhagia. 2- To compare this&#xD;
      proportion according to the four molecules of oral anticoagulants (fluindione, warfarin,&#xD;
      rivaroxaban and apixaban) and 3- to evaluate the impact of these haemorrhages on the quality&#xD;
      of life. Our study would have a control group of women of childbearing age followed in&#xD;
      vascular medicine for superficial venous insufficiency without thrombosis and without oral&#xD;
      anticoagulant because the proportion of genital haemorrhages in women of childbearing age in&#xD;
      PACA region is not known.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 15, 2019</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">January 2023</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Proportion of women with a major genital haemorrhage and/or a minor genital haemorrhage but clinically significant and/or a minor haemorrhage.</measure>
    <time_frame>up to week 6</time_frame>
    <description>Major genital haemorrhage : anemia (&lt;12g/dl), transfusion ≥2 RBC (red blood concentrate) Clinically significant and/or a minor haemorrhage : FIGO recommendations (menstruation more than 8 days, inter menstrual bleeding, presence of blood clots, resort to health professionnal, dose or treatment modification Minor haemorrhage : semi-quantitated score Pictorial Blood Assessment Chart &gt;100 (PBAC)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life score measured with WHOQOL-BREF scale ( World Health Organization Quality of Life)</measure>
    <time_frame>Day 1 and week 6</time_frame>
    <description>WHOQOL-BREF scale comprises 26 items with 5 level of answer (&quot;very poor&quot; to &quot;very good&quot;), each answer give 4 scores 0 to 100 (higher scores = high level of quality of life) for the 4 domains following : physical health, mental health, social relationship and environment.</description>
  </secondary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Anticipated">575</enrollment>
  <condition>Genital Haemorrhage</condition>
  <arm_group>
    <arm_group_label>Warfarine</arm_group_label>
    <description>Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Warfarine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluindione</arm_group_label>
    <description>Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Fluindione</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rivaroxaban</arm_group_label>
    <description>Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Rivaroxaban</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Apixaban</arm_group_label>
    <description>Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Apixaban</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Women in childbearing age with superficial venous insufficiency without treatment oral anticoagulant or antiplatelet.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patient in childbaering age and major followed by a vascular doctor in Provence Alpes Côtes&#xD;
        d'Azur region by one of the investigator centers or one of the 120 doctors in Association&#xD;
        Régionale des Médecins Vasculaires ARMV PACA.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria E+ :&#xD;
&#xD;
          -  Patient in childbearing age and &gt;18 years&#xD;
&#xD;
          -  Venous thromboembolic disease&#xD;
&#xD;
          -  Oral anticoagulant treatment (fluindione, warfarine, rivaroxaban ou apixaban)&#xD;
&#xD;
          -  Following by vascular doctor of Association Régionale des Médecins Vasculaires (ARMV)&#xD;
             PACA (120 doctors) and/or one of the investigator center&#xD;
&#xD;
          -  Affiliated with the Social Security Scheme&#xD;
&#xD;
          -  Received an oral information&#xD;
&#xD;
        Inclusion Criteria E- :&#xD;
&#xD;
          -  Patient in childbearing age and &gt;18 years&#xD;
&#xD;
          -  Superficial venous insufficiency&#xD;
&#xD;
          -  No treatment with oral anticoagulant or anti platelet to not interfere with&#xD;
             haemorrhage risk&#xD;
&#xD;
          -  Following by vascular doctor of Association Régionale des Médecins Vasculaires (ARMV)&#xD;
             PACA (120 doctors) and/or one of the investigator center&#xD;
&#xD;
          -  Affiliated with the Social Security Scheme&#xD;
&#xD;
          -  Received an oral information&#xD;
&#xD;
          -  Non opposition register&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt;18 years patient&#xD;
&#xD;
          -  Woman whose pregnancy is known&#xD;
&#xD;
          -  Pre menopause&#xD;
&#xD;
          -  Absence of menstruation&#xD;
&#xD;
          -  Refusal to participate in the study&#xD;
&#xD;
          -  No answer to the second call&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean Olivier Arnaud</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique Hôpiaux Marseille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gabrielle Sarlon-Bartoli, Dr</last_name>
    <phone>+33(0)4 91 38 70 23</phone>
    <email>gabrielle.sarlon@ap-hm.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Assistance Publique Hôpitaux Marseille</name>
      <address>
        <city>Marseille Cedex 05</city>
        <state>Bouches Du Rhônes</state>
        <zip>13354</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Gabrielle Sarlon-Bartoli, Dr</last_name>
      <phone>+33(0)4 91 38 70 23</phone>
      <email>gabrielle.sarlon@ap-hm.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>December 14, 2018</last_update_submitted>
  <last_update_submitted_qc>December 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <!-- 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/NCT03772366
org study id: 2018-17
nct id: NCT03772366
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Little data are available on the genital haemorrhages in woman of childbearing age treated
      for venous thromboembolic disease by oral anticoagulant, especially the impact on the quality
      of life. A recent systematic review in 2016 described for the first time in patients with
      venous thromboembolic a lower incidence in men of major haemorrhages and minor haemorrhages
      but clinically significant compared with women (5,3% and 7,9% respectively; RR: 0,635, 95%CI
      0,54-0,74 ; p<0,001). It appears that this difference is related to genital haemorrhages and
      some direct oral anticoagulants are more associated with hemorrhagic surge. In post-hoc
      analyzes of phases III trials, rivaroxaban was most of the time associated with genital
      haemorrhages compared to vitamine K antagonists, effect not found with apixaban. Four other
      retrospective studies seem to find the same conclusions with a higher haemorrhagic risk with
      the rivaroxaban than with vitamine K antagonist or apixaban.

      However, haemorrhagic risk is defined in these studies with criteria of severity (anemia,
      transfusion, use of a health professional, menstrual periods of more than 8 days, inter
      mentrual bleeding, presence of blood clots) and these studies do not take into account of
      minor haemorrhages that may affect on the quality of life and asthenia due to anemia.

      Our objective is : 1- studying the proportion of women with abnormal genital haemorrhages
      among women of childbearing age treated for venous thromboembolism disease by oral
      anticoagulant including using a semi quantitative score of menorrhagia. 2- To compare this
      proportion according to the four molecules of oral anticoagulants (fluindione, warfarin,
      rivaroxaban and apixaban) and 3- to evaluate the impact of these haemorrhages on the quality
      of life. Our study would have a control group of women of childbearing age followed in
      vascular medicine for superficial venous insufficiency without thrombosis and without oral
      anticoagulant because the proportion of genital haemorrhages in women of childbearing age in
      PACA region is not known.
observational model: Cohort
time perspective: Prospective
measure: Proportion of women with a major genital haemorrhage and/or a minor genital haemorrhage but clinically significant and/or a minor haemorrhage.
time frame: up to week 6
description: Major genital haemorrhage : anemia (<12g/dl), transfusion ≥2 RBC (red blood concentrate) Clinically significant and/or a minor haemorrhage : FIGO recommendations (menstruation more than 8 days, inter menstrual bleeding, presence of blood clots, resort to health professionnal, dose or treatment modification Minor haemorrhage : semi-quantitated score Pictorial Blood Assessment Chart >100 (PBAC)
measure: Quality of life score measured with WHOQOL-BREF scale ( World Health Organization Quality of Life)
time frame: Day 1 and week 6
description: WHOQOL-BREF scale comprises 26 items with 5 level of answer ("very poor" to "very good"), each answer give 4 scores 0 to 100 (higher scores = high level of quality of life) for the 4 domains following : physical health, mental health, social relationship and environment.
arm group label: Warfarine
description: Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Warfarine
arm group label: Fluindione
description: Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Fluindione
arm group label: Rivaroxaban
description: Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Rivaroxaban
arm group label: Apixaban
description: Women in childbearing age treated for a venous thromboembolic disease with oral coagulant : Apixaban
arm group label: Control
description: Women in childbearing age with superficial venous insufficiency without treatment oral anticoagulant or antiplatelet.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean Olivier Arnaud
role: Study Director
affiliation: Assistance Publique Hôpiaux Marseille
last name: Gabrielle Sarlon-Bartoli, Dr
phone: +33(0)4 91 38 70 23
email: gabrielle.sarlon@ap-hm.fr
facility: 
contact: 
country: France
responsible party type: Sponsor
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Hemorrhage