<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/NCT04433481</url>
  </required_header>
  <id_info>
    <org_study_id>ILBS-Cirrhosis-30</org_study_id>
    <nct_id>NCT04433481</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Dabigatran in Patients With Cirrhosis and Portal Vein Thrombosis</brief_title>
  <official_title>Efficacy and Safety of Dabigatran in Patients With Cirrhosis and Portal Vein Thrombosis-A Randomized Placebo Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Liver and Biliary Sciences, India</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Liver and Biliary Sciences, India</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized controlled trial to study the efficacy and safety of Dabigatran in Cirrhotic&#xD;
      patients who develop PVT.In this study the patients who meet the inclusion criteria will be&#xD;
      randomized to either receive Dabigatran or placebo [multivitamin tablet]. Blood samples will&#xD;
      be taken &amp;Imaging will be done accordingly to notice progression or recanalization of PVT.The&#xD;
      patients are followed up every 2 months up to 18 month .Then statistical analysis will be&#xD;
      done to find whether the Dabigatran is efficacious in cirrhotic patients for recanalization&#xD;
      of PVT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study population -All the patients of cirrhosis of liver patients visiting to ILBS and&#xD;
      diagnosed to have non tumor portal vein thrombosis will be enrolled in the study.&#xD;
&#xD;
      Study Design - A Placebo Controlled Double Blinded RCT In this randomized controlled trial,&#xD;
      the patients who satisfy the below inclusion and exclusion criteria will be included and they&#xD;
      will be randomized, according to 2 groups (in total 84patients) to receive either Placebo or&#xD;
      dabigatran 150 mg BD for 12months. These patients will be admitted to the hospital from OPD&#xD;
      or emergency.&#xD;
&#xD;
      Study period - 1.5 years from ethics approval Intervention The patients in Group A will&#xD;
      receive T. Dabigatran 150 mg twice a day .The patients in Group B will receive placebo&#xD;
      [multivitamins] Monitoring and assessment At baseline, a complete history with clinical and&#xD;
      physical examination, a record of demographic profile, standard of care biochemical&#xD;
      investigations would be done. All included patients will be evaluated with -&#xD;
&#xD;
        1. Etiology of cirrhosis&#xD;
&#xD;
        2. Upper GI endoscopy&#xD;
&#xD;
        3. Haemogram (including reticulocyte count)&#xD;
&#xD;
        4. Coagulogram- PT/INR,APTT,TEG&#xD;
&#xD;
        5. Prothrombotic profile- protein c/protein-s/AT-III/Factor V Leiden mutation/ MTHFR&#xD;
           C677T/PROTHROMBIN G20210A/ JAK2 V617F MUTATION / Anticardiolipin Ab.&#xD;
&#xD;
        6. Liver function tests, Renal function tests&#xD;
&#xD;
        7. Alpha fetoprotein/PIVKA II&#xD;
&#xD;
        8. USG abdomen with Doppler study&#xD;
&#xD;
        9. CECT-TP or CEMRI-TP to R/O HCC or angiography when PVT diagnosis doubtful.&#xD;
&#xD;
       10. HVPG+LIVER BIOPSY[optional]&#xD;
&#xD;
       11. Fibro scan&#xD;
&#xD;
       12. Child-Pugh score, MELD Subsequently, patients will be assessed clinically at the&#xD;
           baseline and post-treatment every2 months till 18 months&#xD;
&#xD;
      Statistical Analysis:&#xD;
&#xD;
      The data collected will be analyzed using SPSS ver 22 by standard statistical analysis, were&#xD;
      numerical data will be analyzed to find mean, median scores and categorical data will be&#xD;
      analyzed using Chi square test and continuous data will be analyzed by student T test and any&#xD;
      association will be analyzed by the univariate and multivariate analysis, log regression&#xD;
      analysis along with ROC curve will be used and p&lt;0.05 will be considered significant and&#xD;
      results will be appropriately tabulated&#xD;
&#xD;
      Adverse Effects Hemorrhage - Fatal Major - intracranial, retroperitoneal, intraocular, muscle&#xD;
      hematoma Minor TREATMENT IN CASE OF ADVERSE EFFECTS - Withdrawal of drug&#xD;
&#xD;
      Stopping rule of study Allergic reactions to drug Severe hemorrhage DIC Progression of PVT&#xD;
      after 6 months viral reactivation leading to ACLF, acute hepatitis (viral, drug related,&#xD;
      autoimmune flare), sepsis with severe coagulopathy&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 20, 2020</start_date>
  <completion_date type="Anticipated">May 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2022</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with complete recanalization of thrombus in both groups.</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with partial recanalization of thrombus in both groups.</measure>
    <time_frame>1 Year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups.</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvements in Model for End Stage Liver Disease (MELD) Score in both groups</measure>
    <time_frame>6 months</time_frame>
    <description>MELD score ranges from 6 to 40.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvements in Model for End Stage Liver Disease (MELD) Score in both groups</measure>
    <time_frame>1 Year</time_frame>
    <description>MELD score ranges from 6 to 40.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with prevention of secondary decompensation in both groups</measure>
    <time_frame>1 Year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events in both groups</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time).</measure>
    <time_frame>6 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time).</measure>
    <time_frame>12 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with reduction in clinical complications in patients with PVT in both groups</measure>
    <time_frame>3 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with reduction in clinical complications in patients with PVT in both groups</measure>
    <time_frame>6 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with reduction in clinical complications in patients with PVT in both groups</measure>
    <time_frame>12 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the number of participants developing reoccurrence of PVT after treatment with Dabigatran for 12 months by Ultrasound Doppler of splenoportal venous system.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine predictors for recurrence of PVT in patients with cirrhosis.</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the predictors of development of PVT in the population of cirrhosis patients screened who did not have PVT at the initiation of the study, for the development of new PVT over the period of the study</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">84</enrollment>
  <condition>Liver Cirrhosis</condition>
  <condition>Portal Vein Thrombosis</condition>
  <arm_group>
    <arm_group_label>DABIGATRAN</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>150mg BD for 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabigatran</intervention_name>
    <description>T. Dabigatran 150 mg twice a day</description>
    <arm_group_label>DABIGATRAN</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinical / radiological /histologic diagnosis of cirrhosis [Childs A&amp;B - CTP&lt;9]&#xD;
&#xD;
          2. Partial / total portal vein thrombosis (chronic)&#xD;
&#xD;
          3. Age- 18-70 years&#xD;
&#xD;
          4. Valid consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &gt; 70 years&#xD;
&#xD;
          2. Presence of active infection (&lt;2 weeks)&#xD;
&#xD;
          3. Use of anticoagulant drugs in the past 10 days&#xD;
&#xD;
          4. Pregnancy&#xD;
&#xD;
          5. HIV positivity&#xD;
&#xD;
          6. Recent (&lt;7 days) transfusion with blood products.&#xD;
&#xD;
          7. History of bleeding in last 42 days&#xD;
&#xD;
          8. HCC / Other malignancy&#xD;
&#xD;
          9. Chronic kidney disease [ CrCl&lt; 30]&#xD;
&#xD;
         10. Drug allergies&#xD;
&#xD;
         11. PVT with cavernoma formation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Dr G. Srinivasa Reddy, MD</last_name>
    <phone>01146300000</phone>
    <email>srinivasareddygolamari@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Liver &amp; Biliary Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110070</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr G Srinivasa Reddy, MD</last_name>
      <phone>01146300000</phone>
      <email>srinivasareddygolamari@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>August 19, 2021</last_update_submitted>
  <last_update_submitted_qc>August 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</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>Liver Cirrhosis</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>Dabigatran</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04433481
org study id: ILBS-Cirrhosis-30
nct id: NCT04433481
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A randomized controlled trial to study the efficacy and safety of Dabigatran in Cirrhotic
      patients who develop PVT.In this study the patients who meet the inclusion criteria will be
      randomized to either receive Dabigatran or placebo [multivitamin tablet]. Blood samples will
      be taken &Imaging will be done accordingly to notice progression or recanalization of PVT.The
      patients are followed up every 2 months up to 18 month .Then statistical analysis will be
      done to find whether the Dabigatran is efficacious in cirrhotic patients for recanalization
      of PVT.
Study population -All the patients of cirrhosis of liver patients visiting to ILBS and
      diagnosed to have non tumor portal vein thrombosis will be enrolled in the study.

      Study Design - A Placebo Controlled Double Blinded RCT In this randomized controlled trial,
      the patients who satisfy the below inclusion and exclusion criteria will be included and they
      will be randomized, according to 2 groups (in total 84patients) to receive either Placebo or
      dabigatran 150 mg BD for 12months. These patients will be admitted to the hospital from OPD
      or emergency.

      Study period - 1.5 years from ethics approval Intervention The patients in Group A will
      receive T. Dabigatran 150 mg twice a day .The patients in Group B will receive placebo
      [multivitamins] Monitoring and assessment At baseline, a complete history with clinical and
      physical examination, a record of demographic profile, standard of care biochemical
      investigations would be done. All included patients will be evaluated with -

        1. Etiology of cirrhosis

        2. Upper GI endoscopy

        3. Haemogram (including reticulocyte count)

        4. Coagulogram- PT/INR,APTT,TEG

        5. Prothrombotic profile- protein c/protein-s/AT-III/Factor V Leiden mutation/ MTHFR
           C677T/PROTHROMBIN G20210A/ JAK2 V617F MUTATION / Anticardiolipin Ab.

        6. Liver function tests, Renal function tests

        7. Alpha fetoprotein/PIVKA II

        8. USG abdomen with Doppler study

        9. CECT-TP or CEMRI-TP to R/O HCC or angiography when PVT diagnosis doubtful.

       10. HVPG+LIVER BIOPSY[optional]

       11. Fibro scan

       12. Child-Pugh score, MELD Subsequently, patients will be assessed clinically at the
           baseline and post-treatment every2 months till 18 months

      Statistical Analysis:

      The data collected will be analyzed using SPSS ver 22 by standard statistical analysis, were
      numerical data will be analyzed to find mean, median scores and categorical data will be
      analyzed using Chi square test and continuous data will be analyzed by student T test and any
      association will be analyzed by the univariate and multivariate analysis, log regression
      analysis along with ROC curve will be used and p<0.05 will be considered significant and
      results will be appropriately tabulated

      Adverse Effects Hemorrhage - Fatal Major - intracranial, retroperitoneal, intraocular, muscle
      hematoma Minor TREATMENT IN CASE OF ADVERSE EFFECTS - Withdrawal of drug

      Stopping rule of study Allergic reactions to drug Severe hemorrhage DIC Progression of PVT
      after 6 months viral reactivation leading to ACLF, acute hepatitis (viral, drug related,
      autoimmune flare), sepsis with severe coagulopathy
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of participants with complete recanalization of thrombus in both groups.
time frame: 1 year
measure: Number of participants with partial recanalization of thrombus in both groups.
time frame: 1 Year
measure: Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups.
time frame: 6 months
measure: Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups.
time frame: 1 year
measure: Improvements in Model for End Stage Liver Disease (MELD) Score in both groups
time frame: 6 months
description: MELD score ranges from 6 to 40.
measure: Improvements in Model for End Stage Liver Disease (MELD) Score in both groups
time frame: 1 Year
description: MELD score ranges from 6 to 40.
measure: Number of participants with prevention of secondary decompensation in both groups
time frame: 1 Year
measure: Adverse Events in both groups
time frame: 1 year
measure: To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time).
time frame: 6 Months
measure: To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time).
time frame: 12 Months
measure: Number of participants with reduction in clinical complications in patients with PVT in both groups
time frame: 3 Months
measure: Number of participants with reduction in clinical complications in patients with PVT in both groups
time frame: 6 Months
measure: Number of participants with reduction in clinical complications in patients with PVT in both groups
time frame: 12 Months
measure: To study the number of participants developing reoccurrence of PVT after treatment with Dabigatran for 12 months by Ultrasound Doppler of splenoportal venous system.
time frame: 12 months
measure: To determine predictors for recurrence of PVT in patients with cirrhosis.
time frame: 1 year
measure: To study the predictors of development of PVT in the population of cirrhosis patients screened who did not have PVT at the initiation of the study, for the development of new PVT over the period of the study
time frame: 1 year
arm group label: DABIGATRAN
arm group type: Experimental
description: 150mg BD for 12 months
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Dabigatran
description: T. Dabigatran 150 mg twice a day
arm group label: DABIGATRAN
intervention type: Other
intervention name: Placebo
description: placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Dr G. Srinivasa Reddy, MD
phone: 01146300000
email: srinivasareddygolamari@gmail.com
facility: 
status: Recruiting
contact: 
country: India
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Fibrosis
mesh term: Dabigatran
sharing ipd: Undecided