<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/NCT02240927</url>
  </required_header>
  <id_info>
    <org_study_id>KOSUYOLU1</org_study_id>
    <nct_id>NCT02240927</nct_id>
  </id_info>
  <brief_title>Anticoagulation Regimens in Pregnant Patients With Prosthetic Heart Valves</brief_title>
  <official_title>Comparison of Different Anticoagulation Regimens in Pregnant Patients With Prosthetic Heart Valves: A Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pregnancy is associated with increased risk of thrombosis among women with mechanical&#xD;
      prosthetic heart valves.However, the best anticoagulant treatment strategies for pregnant&#xD;
      patients with prosthetic heart valves have been controversial. In this study the&#xD;
      investigators wanted to identify the most effective and safe regimen among different&#xD;
      anticoagulant regimens.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Four different anticoagulant treatment regimens for pregnant patients with prosthetic heart&#xD;
      valves have been described. In the first arm warfarin is stopped and enoxaparine is started&#xD;
      in 1mg/kg dose twice a day which is monitored by weekly anti-Xa levels (between 0.7-1.2)&#xD;
      during the first trimester and followed by only warfarin after first trimester. In the second&#xD;
      arm, if the patient's warfarin consumption is more than 5 mg before pregnancy, warfarin dose&#xD;
      is decreased to 2.5 mg during the first trimester combined with enoxaparine in 1mg/kg dose&#xD;
      twice a day; adjusted by measurements of anti-Xa levels (between 0.5-1) weekly until the end&#xD;
      of 12th week of pregnancy . In the third arm warfarin dose is decreased to 4 mg during the&#xD;
      first trimester combined with enoxaparine given in a similar manner. If the patient's&#xD;
      therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the&#xD;
      same dose during all the pregnancy in the 4th arm. All patients are followed by serial&#xD;
      transesophageal echocardiography performed at 0,3,6 and 9. months of pregnancy. Informed&#xD;
      consent is taken from all patients. After delivery the babies are examined by a experinced&#xD;
      pediatrician and pediatric cardiologist for any congenital anomalies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2010</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">June 2015</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Successful pregnancy</measure>
    <time_frame>12 month</time_frame>
    <description>In the absence of fetal and maternal fatal or nonfatal major complications successful pregnancy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maternal Complications</measure>
    <time_frame>Participants will be followed during pregnancy and postpartum period, an expected average of 12 months</time_frame>
    <description>Nonfatal major complication: Ischemic stroke, intracranial hemorrhage, embolism (coronary or peripheral), bleeding requiring transfusion, abortus, placental hemorrhage, Assessment of an increase in thrombus burden more than 50% and/or progression of PVT obstruction by transesophageal echocardiography.&#xD;
Nonfatal minor complication: Bleeding without need for transfusion, TIA.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fetal Complications</measure>
    <time_frame>12 months</time_frame>
    <description>Any congenital anomalia which may be attributed to warfarin or enoxaparine usage during pregnancy</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Pregnancy</condition>
  <condition>Heart; Complications, Valve, Prosthesis</condition>
  <arm_group>
    <arm_group_label>Enoxaparine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>During first trimester, warfarin is stopped and enoxaparine is started in 1mg/kg dose twice a day. Dose is adjusted according to Anti Factor Xa levels (between 0.7-1.2). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enoxaparine and 2.5 mg warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>If the patient's therapeutic warfarin dose is more than 5 mg before pregnancy, warfarin dose is decreased to 2.5 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1.0). Full dose warfarin is continued after first trimester and dose is regulated according to INR (between 2.5-4)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enoxaparine and 4 mg warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>If the patient's warfarin consumption dose is more than 5 mg before pregnancy, warfarin dose is decreased to 4 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>If the patient's therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the same dose during all the pregnancy and the dose is adjusted according to INR level (between 2.5-4).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low Molecular Weight Heparine : Enoxaparine</intervention_name>
    <description>During first trimester, warfarin is stopped and enoxaparine is started in 1mg/kg dose twice a day. Dose is adjusted according to Anti Factor Xa levels (between 0.7-1.2). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).</description>
    <arm_group_label>Enoxaparine</arm_group_label>
    <other_name>Clexane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparine and 2.5 mg Warfarin</intervention_name>
    <description>If the patient's therapeutic warfarin dose is more than 5 mg before pregnancy, warfarin dose is decreased to 2.5 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4)</description>
    <arm_group_label>Enoxaparine and 2.5 mg warfarin</arm_group_label>
    <other_name>Clexane and 2.5 mg Warfarin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparine and 4mg Warfarin</intervention_name>
    <description>If the patient's warfarin consumption dose is more than 5 mg before pregnancy, warfarin dose is decreased to 4 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).</description>
    <arm_group_label>Enoxaparine and 4 mg warfarin</arm_group_label>
    <other_name>Clexane and 4 mg Warfarin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <description>If the patient's therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the same dose during all the pregnancy and the dose is adjusted according to INR level (between 2.5-4).</description>
    <arm_group_label>Warfarin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant patients with prosthetic heart valves&#xD;
&#xD;
        Exclusion Criteria:&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mehmet Ozkan, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kosuyolu Kartal Heart Training and Research Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>MEHMET OZKAN, PROF</last_name>
    <phone>+905322551513</phone>
    <email>memoozkan1@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Kosuyolu Kartal Heart Training and Research Hospital</name>
      <address>
        <city>Istanbul</city>
        <zip>34844</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mehmet Ozkan, Prof</last_name>
      <phone>+905322551512</phone>
      <email>memoozkan1@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Mehmet Ozkan, Prof</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>September 15, 2014</last_update_submitted>
  <last_update_submitted_qc>September 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital</investigator_affiliation>
    <investigator_full_name>MEHMET OZKAN</investigator_full_name>
    <investigator_title>Principal Investigator, MD., Prof., Head of Cardiology</investigator_title>
  </responsible_party>
  <keyword>Anticoagulation</keyword>
  <keyword>Prosthetic Heart Valves</keyword>
  <keyword>Pregnancy</keyword>
  <keyword>Warfarin</keyword>
  <keyword>Thrombosis</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Enoxaparin sodium</mesh_term>
  </intervention_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/NCT02240927
org study id: KOSUYOLU1
nct id: NCT02240927
lead sponsor: 
has dmc: No
Pregnancy is associated with increased risk of thrombosis among women with mechanical
      prosthetic heart valves.However, the best anticoagulant treatment strategies for pregnant
      patients with prosthetic heart valves have been controversial. In this study the
      investigators wanted to identify the most effective and safe regimen among different
      anticoagulant regimens.
Four different anticoagulant treatment regimens for pregnant patients with prosthetic heart
      valves have been described. In the first arm warfarin is stopped and enoxaparine is started
      in 1mg/kg dose twice a day which is monitored by weekly anti-Xa levels (between 0.7-1.2)
      during the first trimester and followed by only warfarin after first trimester. In the second
      arm, if the patient's warfarin consumption is more than 5 mg before pregnancy, warfarin dose
      is decreased to 2.5 mg during the first trimester combined with enoxaparine in 1mg/kg dose
      twice a day; adjusted by measurements of anti-Xa levels (between 0.5-1) weekly until the end
      of 12th week of pregnancy . In the third arm warfarin dose is decreased to 4 mg during the
      first trimester combined with enoxaparine given in a similar manner. If the patient's
      therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the
      same dose during all the pregnancy in the 4th arm. All patients are followed by serial
      transesophageal echocardiography performed at 0,3,6 and 9. months of pregnancy. Informed
      consent is taken from all patients. After delivery the babies are examined by a experinced
      pediatrician and pediatric cardiologist for any congenital anomalies.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Successful pregnancy
time frame: 12 month
description: In the absence of fetal and maternal fatal or nonfatal major complications successful pregnancy
measure: Maternal Complications
time frame: Participants will be followed during pregnancy and postpartum period, an expected average of 12 months
description: Nonfatal major complication: Ischemic stroke, intracranial hemorrhage, embolism (coronary or peripheral), bleeding requiring transfusion, abortus, placental hemorrhage, Assessment of an increase in thrombus burden more than 50% and/or progression of PVT obstruction by transesophageal echocardiography.
Nonfatal minor complication: Bleeding without need for transfusion, TIA.
measure: Fetal Complications
time frame: 12 months
description: Any congenital anomalia which may be attributed to warfarin or enoxaparine usage during pregnancy
arm group label: Enoxaparine
arm group type: Active Comparator
description: During first trimester, warfarin is stopped and enoxaparine is started in 1mg/kg dose twice a day. Dose is adjusted according to Anti Factor Xa levels (between 0.7-1.2). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).
arm group label: Enoxaparine and 2.5 mg warfarin
arm group type: Active Comparator
description: If the patient's therapeutic warfarin dose is more than 5 mg before pregnancy, warfarin dose is decreased to 2.5 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1.0). Full dose warfarin is continued after first trimester and dose is regulated according to INR (between 2.5-4)
arm group label: Enoxaparine and 4 mg warfarin
arm group type: Active Comparator
description: If the patient's warfarin consumption dose is more than 5 mg before pregnancy, warfarin dose is decreased to 4 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).
arm group label: Warfarin
arm group type: Active Comparator
description: If the patient's therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the same dose during all the pregnancy and the dose is adjusted according to INR level (between 2.5-4).
intervention type: Drug
intervention name: Low Molecular Weight Heparine : Enoxaparine
description: During first trimester, warfarin is stopped and enoxaparine is started in 1mg/kg dose twice a day. Dose is adjusted according to Anti Factor Xa levels (between 0.7-1.2). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).
arm group label: Enoxaparine
other name: Clexane
intervention type: Drug
intervention name: Enoxaparine and 2.5 mg Warfarin
description: If the patient's therapeutic warfarin dose is more than 5 mg before pregnancy, warfarin dose is decreased to 2.5 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4)
arm group label: Enoxaparine and 2.5 mg warfarin
other name: Clexane and 2.5 mg Warfarin
intervention type: Drug
intervention name: Enoxaparine and 4mg Warfarin
description: If the patient's warfarin consumption dose is more than 5 mg before pregnancy, warfarin dose is decreased to 4 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).
arm group label: Enoxaparine and 4 mg warfarin
other name: Clexane and 4 mg Warfarin
intervention type: Drug
intervention name: Warfarin
description: If the patient's therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the same dose during all the pregnancy and the dose is adjusted according to INR level (between 2.5-4).
arm group label: Warfarin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Mehmet Ozkan, Prof
role: Principal Investigator
affiliation: Kosuyolu Kartal Heart Training and Research Hospital
last name: MEHMET OZKAN, PROF
phone: +905322551513
email: memoozkan1@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
investigator full name: MEHMET OZKAN
investigator title: Principal Investigator, MD., Prof., Head of Cardiology
mesh term: Enoxaparin
mesh term: Warfarin
mesh term: Enoxaparin sodium