<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/NCT02247414</url>
  </required_header>
  <id_info>
    <org_study_id>YZUC-002</org_study_id>
    <nct_id>NCT02247414</nct_id>
  </id_info>
  <brief_title>Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection</brief_title>
  <acronym>ESWAPH</acronym>
  <official_title>Efficacy and Safety of Warfarin Anticoagulation for Prevention of Portal Vein Thrombosis in Liver Cirrhotic Patients After Laparoscopic Splenectomy and Azygoportal Disconnection for Portal Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yangzhou University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yangzhou University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether Warfarin Anticoagulation are effective and&#xD;
      safe in Prevention of Portal Vein Thrombosis in Liver Cirrhotic Patients after Laparoscopic&#xD;
      Splenectomy and Azygoportal Disconnection for Portal Hypertension&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After successful screening the cases of cirrhosis of liver irrespective of the etiology who&#xD;
      have non tumor portal vein thrombosis will be enrolled. The baseline Doppler parameter will&#xD;
      be recorded and the patient will be randomized into either interventional (warfarin) or&#xD;
      control (aspirin) group. From postoperative day 3, patients in interventional (warfarin)&#xD;
      group will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of&#xD;
      2-3 for 1 year, patients in control (aspirin) group will receive oral Aspirin Enterie Ccoated&#xD;
      Tablets 100mg qd for 1 year, and both groups will be along with five days of subcutaneous&#xD;
      injection of Low Molecular Weight Heparin and three months of oral Dipyridamole. Every 3&#xD;
      months the Doppler screening for the occurrence of portal vein thrombus (PVT) or&#xD;
      spleno-mesenteric thrombosis will be done for all patients. Both groups will receive the&#xD;
      therapy for one year irrespective of the Doppler findings in relation to portal vein thrombus&#xD;
      occurrence. Then one year monitoring will be done in the both groups as per the primary or&#xD;
      secondary outcome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">September 2017</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportions of patients who will suffer PVT or spleno-mesenteric thrombosis between oral anticoagulant Warfarin with dipyridamole group and oral Aspirin with dipyridamole group during the study period of 3 year from randomization</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportions of patients who will show improvement in Child Pugh (&gt;2 points)in both groups</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportions of patients who will show improvement in Model for End Stage Liver Disease (MELD)(&gt;4 points)in both groups</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportions of patients who will show decrease in hepatic decompensation defined as development of ascites, PSE, portal hypertensive bleeding, jaundice, spontaneous bacterial peritonitis, or systemic infection</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportions of patients who will suffer from hepatocellular carcinoma in both groups</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival in both groups</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">124</enrollment>
  <condition>Cirrhosis</condition>
  <condition>Hypertension</condition>
  <condition>Status;Splenectomy</condition>
  <condition>Venous Thrombosis</condition>
  <arm_group>
    <arm_group_label>Warfarin with dipyridamole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>From postoperative day 3, patients will receive dipyridamole 25mg tid for three months along with subcutaneous Low Molecular Weight Heparin Calcium injection for first five days and Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3. Intially the INR will be monitored twice weekly with gradual escalation of dose to achieve target INR. After achieving the target INR, this is to be repeated every 4 weeks. The Doppler Ultra Sonography screening will be done every 3 months to assess the occurrence of portal vein thrombus, but the medications will be continue for one year irrespective of the occurrence of portal vein thrombus.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin with dipyridamole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months along with subcutaneous injection of Low Molecular Weight Heparin (4100 IU) for first five days and Aspirin Enterie Ccoated Tablets 100mg qd for one year.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <description>From postoperative day 3, patients will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3 for 1 year.</description>
    <arm_group_label>Warfarin with dipyridamole</arm_group_label>
    <other_name>Warfarin Sodium</other_name>
    <other_name>Athrombine</other_name>
    <other_name>COUMADIN</other_name>
    <other_name>PANAWARFIN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dipyridamole</intervention_name>
    <description>From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months.</description>
    <arm_group_label>Aspirin with dipyridamole</arm_group_label>
    <arm_group_label>Warfarin with dipyridamole</arm_group_label>
    <other_name>Gardoxin</other_name>
    <other_name>Coribon</other_name>
    <other_name>Curantyl</other_name>
    <other_name>Dilaplus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <description>From postoperative day 3, patients will receive oral Aspirin Enterie Ccoated Tablets 100mg qd for 1 year.</description>
    <arm_group_label>Aspirin with dipyridamole</arm_group_label>
    <other_name>Acenterine</other_name>
    <other_name>Acetard</other_name>
    <other_name>Acetophen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low Molecular Weight Heparin</intervention_name>
    <description>From postoperative day 3, patients will receive subcutaneous injection of Low Molecular Weight Heparin (4100 IU) once daily for first five days.</description>
    <arm_group_label>Aspirin with dipyridamole</arm_group_label>
    <arm_group_label>Warfarin with dipyridamole</arm_group_label>
    <other_name>Fraxiparine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A clinical, radiological or histologic diagnosis of cirrhosis of any etiology&#xD;
&#xD;
          -  Splenomegaly with secondary hypersplenism&#xD;
&#xD;
          -  Bleeding portal hypertension&#xD;
&#xD;
          -  INo evidence of PVT or spleno-mesenteric thrombosis by ultrasound evaluation and&#xD;
             angio-CT&#xD;
&#xD;
          -  Informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hepatocellular carcinoma or any other malignancy&#xD;
&#xD;
          -  Hypercoagulable state other than the liver disease related&#xD;
&#xD;
          -  DRUGS- oral contraceptives, anticoagulation or anti-platelet drugs&#xD;
&#xD;
          -  Base line INR &gt;2&#xD;
&#xD;
          -  Child-Pugh grade C&#xD;
&#xD;
          -  Recent peptic ulcer disease&#xD;
&#xD;
          -  History of Hemorrhagic stroke&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Uncontrolled Hypertension&#xD;
&#xD;
          -  Age&gt;75 yrs&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dou-Sheng Bai, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Clinical Medical College of Yangzhou University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Guo-Qing Jiang, MS</last_name>
    <role>Study Director</role>
    <affiliation>Clinical Medical College of Yangzhou University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ping Chen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Medical College of Yangzhou University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sheng-Jie Jin, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Medical College of Yangzhou University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Medical College of Yangzhou University</name>
      <address>
        <city>Yangzhou</city>
        <state>Jiangsu</state>
        <zip>225001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>March 28, 2019</last_update_submitted>
  <last_update_submitted_qc>March 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yangzhou University</investigator_affiliation>
    <investigator_full_name>Guo-Qing Jiang</investigator_full_name>
    <investigator_title>Master</investigator_title>
  </responsible_party>
  <keyword>Cirrhosis</keyword>
  <keyword>Hypertension</keyword>
  <keyword>venous thrombosis</keyword>
  <keyword>Warfarin</keyword>
  <keyword>Splenectomy</keyword>
  <keyword>Azygoportal Disconnection</keyword>
  <keyword>Laparoscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Heparin</mesh_term>
    <mesh_term>Heparin, Low-Molecular-Weight</mesh_term>
    <mesh_term>Tinzaparin</mesh_term>
    <mesh_term>Dalteparin</mesh_term>
    <mesh_term>Dipyridamole</mesh_term>
    <mesh_term>Warfarin</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/NCT02247414
org study id: YZUC-002
nct id: NCT02247414
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether Warfarin Anticoagulation are effective and
      safe in Prevention of Portal Vein Thrombosis in Liver Cirrhotic Patients after Laparoscopic
      Splenectomy and Azygoportal Disconnection for Portal Hypertension
After successful screening the cases of cirrhosis of liver irrespective of the etiology who
      have non tumor portal vein thrombosis will be enrolled. The baseline Doppler parameter will
      be recorded and the patient will be randomized into either interventional (warfarin) or
      control (aspirin) group. From postoperative day 3, patients in interventional (warfarin)
      group will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of
      2-3 for 1 year, patients in control (aspirin) group will receive oral Aspirin Enterie Ccoated
      Tablets 100mg qd for 1 year, and both groups will be along with five days of subcutaneous
      injection of Low Molecular Weight Heparin and three months of oral Dipyridamole. Every 3
      months the Doppler screening for the occurrence of portal vein thrombus (PVT) or
      spleno-mesenteric thrombosis will be done for all patients. Both groups will receive the
      therapy for one year irrespective of the Doppler findings in relation to portal vein thrombus
      occurrence. Then one year monitoring will be done in the both groups as per the primary or
      secondary outcome.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportions of patients who will suffer PVT or spleno-mesenteric thrombosis between oral anticoagulant Warfarin with dipyridamole group and oral Aspirin with dipyridamole group during the study period of 3 year from randomization
time frame: 3 years
measure: Proportions of patients who will show improvement in Child Pugh (>2 points)in both groups
time frame: 3 years
measure: Proportions of patients who will show improvement in Model for End Stage Liver Disease (MELD)(>4 points)in both groups
time frame: 3 years
measure: Proportions of patients who will show decrease in hepatic decompensation defined as development of ascites, PSE, portal hypertensive bleeding, jaundice, spontaneous bacterial peritonitis, or systemic infection
time frame: 3 years
measure: Proportions of patients who will suffer from hepatocellular carcinoma in both groups
time frame: 3 years
measure: Overall survival in both groups
time frame: 3 years
arm group label: Warfarin with dipyridamole
arm group type: Experimental
description: From postoperative day 3, patients will receive dipyridamole 25mg tid for three months along with subcutaneous Low Molecular Weight Heparin Calcium injection for first five days and Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3. Intially the INR will be monitored twice weekly with gradual escalation of dose to achieve target INR. After achieving the target INR, this is to be repeated every 4 weeks. The Doppler Ultra Sonography screening will be done every 3 months to assess the occurrence of portal vein thrombus, but the medications will be continue for one year irrespective of the occurrence of portal vein thrombus.
arm group label: Aspirin with dipyridamole
arm group type: Active Comparator
description: From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months along with subcutaneous injection of Low Molecular Weight Heparin (4100 IU) for first five days and Aspirin Enterie Ccoated Tablets 100mg qd for one year.
intervention type: Drug
intervention name: Warfarin
description: From postoperative day 3, patients will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3 for 1 year.
arm group label: Warfarin with dipyridamole
other name: Warfarin Sodium
other name: Athrombine
other name: COUMADIN
other name: PANAWARFIN
intervention type: Drug
intervention name: Dipyridamole
description: From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months.
arm group label: Aspirin with dipyridamole
arm group label: Warfarin with dipyridamole
other name: Gardoxin
other name: Coribon
other name: Curantyl
other name: Dilaplus
intervention type: Drug
intervention name: Aspirin
description: From postoperative day 3, patients will receive oral Aspirin Enterie Ccoated Tablets 100mg qd for 1 year.
arm group label: Aspirin with dipyridamole
other name: Acenterine
other name: Acetard
other name: Acetophen
intervention type: Drug
intervention name: Low Molecular Weight Heparin
description: From postoperative day 3, patients will receive subcutaneous injection of Low Molecular Weight Heparin (4100 IU) once daily for first five days.
arm group label: Aspirin with dipyridamole
arm group label: Warfarin with dipyridamole
other name: Fraxiparine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dou-Sheng Bai, MD
role: Study Chair
affiliation: Clinical Medical College of Yangzhou University
last name: Guo-Qing Jiang, MS
role: Study Director
affiliation: Clinical Medical College of Yangzhou University
last name: Ping Chen, MD
role: Principal Investigator
affiliation: Clinical Medical College of Yangzhou University
last name: Sheng-Jie Jin, MS
role: Principal Investigator
affiliation: Clinical Medical College of Yangzhou University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Yangzhou University
investigator full name: Guo-Qing Jiang
investigator title: Master
mesh term: Hypertension
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Fibrosis
mesh term: Aspirin
mesh term: Heparin
mesh term: Heparin, Low-Molecular-Weight
mesh term: Tinzaparin
mesh term: Dalteparin
mesh term: Dipyridamole
mesh term: Warfarin
sharing ipd: No