<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/NCT04421924</url>
  </required_header>
  <id_info>
    <org_study_id>TIPS-prospective</org_study_id>
    <nct_id>NCT04421924</nct_id>
  </id_info>
  <brief_title>Periinterventional Coagulation Management of Patients Undergoing a TIPS</brief_title>
  <acronym>TIPSprosp</acronym>
  <official_title>Optimizing Periinterventional Coagulation Management of Patients Undergoing a Transjugular Intrahepatic Portosystemic Shunt Implantation: A Prospective Randomized Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Graz</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>
      Assess whether a pre-interventional thrombelastography guided algorithm for assessing and&#xD;
      correction of coagulation status in cirrhotic patients is safe and effective&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transjugular intrahepatic portosystemic shunt (TIPS) is a very effective procedure to treat&#xD;
      complications of portal hypertension in liver cirrhosis. TIPS implantation is indicated in&#xD;
      cirrhotic patients to treat or prevent portal hypertensive bleeding and to treat refractory&#xD;
      ascites.&#xD;
&#xD;
      During this procedure an artificial connection between portal vein and hepatic vein is placed&#xD;
      via an image-guided endovascular approach. Although the procedure is very effective and&#xD;
      reasonably safe, several complications can occur.&#xD;
&#xD;
      Due to the underlying cirrhosis, morbidity and mortality of TIPS is high, with a 30-day&#xD;
      mortality between 7 and 20%. Procedural site complications (transhepatic and transvenous&#xD;
      access), bleeding, development of hepatic encephalopathy or other organ complications and&#xD;
      stent complications comprise a considerable risk to the patients, however, the improvement of&#xD;
      mortality, renal function and liver function outweighs the risks of the procedure. Optimal&#xD;
      patient selection and preoperative preparation is crucial to avoid complications of this&#xD;
      procedure.&#xD;
&#xD;
      In liver cirrhosis, coagulation disturbances are common. In hepatic insufficiency, a balanced&#xD;
      reduction in the levels of most of pro- and anticoagulant proteins produced in the liver does&#xD;
      not impair thrombin generation until levels are quite low. However, the ability of the&#xD;
      coagulation system to tolerate or recover from an insult is markedly impaired in liver&#xD;
      disease. This allows the coagulation system to be more easily tipped into a state favouring&#xD;
      either haemorrhage or thrombosis. The American Gastroenterology Association has recently&#xD;
      published best practice advices to manage coagulation in cirrhosis. This review concludes&#xD;
      that commonly used global coagulation tests are not optimal to assess the risk of bleeding in&#xD;
      cirrhosis. A randomized controlled trial showed, that the use of thrombelastography (TEG) to&#xD;
      assess coagulation in cirrhosis resulted in a significantly lower usage of blood products&#xD;
      with no increase in bleeding rates.&#xD;
&#xD;
      The bleeding risk for TIPS implantation is not well studied, ranging from 0.6-4.3% of fatal&#xD;
      bleeding complications in older uncontrolled case series. No evidenced-based recommendations&#xD;
      exist for the correction of coagulation abnormalities before TIPS - and the few existing&#xD;
      recommendations are not backed with evidence but rather &quot;eminence based&quot;. Currently, global&#xD;
      tests of coagulation (prothrombin time and platelet count) are used to guide coagulation&#xD;
      correction. Mostly, cut-offs without sufficient evidence (PT &gt;50%/ INR &gt;1.8 and platelets &gt;50&#xD;
      G/L) are used for correction of coagulation.&#xD;
&#xD;
      Also, the risk of stent thrombosis needs to be considered, therefore &quot;blind&quot; substitution of&#xD;
      clotting factors or platelet transfusions is not advisable. Unfortunately, the study by De&#xD;
      Pietri et al. (6) did only include one patient undergoing TIPS (in the standard of care (SOC)&#xD;
      arm), therefore it is yet unknown, whether TEG is useful for guiding the correction of&#xD;
      coagulation abnormalities in cirrhosis.&#xD;
&#xD;
      The aim of this trial is to assess, whether TEG guided pre-interventional assessment and&#xD;
      correction of coagulation in cirrhotic patients is safe and effective&#xD;
&#xD;
      The study will be performed as a single-center, open-label, randomized prospective cohort&#xD;
      study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 27, 2020</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2024</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>blood product requirement</measure>
    <time_frame>2 days</time_frame>
    <description>Amount of blood products (coagulation factors and platelet transfusions) transfused for pre-interventional correction of coagulation status</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bleeding</measure>
    <time_frame>90 days</time_frame>
    <description>Rate of bleeding complications (BARC criteria)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>complications</measure>
    <time_frame>90 days</time_frame>
    <description>Rate of transfusion related complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>90 days</time_frame>
    <description>Mortality rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified TIPS Score (MOTS)</measure>
    <time_frame>90 days</time_frame>
    <description>Predictive power of modified TIPS score (MOTS) using the routine parameter, bilirubin, urea and INR; values range from 0-3, high score means worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Factor XIII</measure>
    <time_frame>2 days</time_frame>
    <description>Comparison of measured FXIII activity levels with TEG parameters (alpha-angle, K-time, MA) for assessing feasibility of TEG in predicting deficiency of FXIII activity in these specific group of patients.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">39</enrollment>
  <condition>Liver Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Thrombelastogram (TEG)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in the TEG group will receive prothrombin complex concentrates (PCC) at a dose of 10 IE/kg of ideal body weight, when R-time was greater than 40 minutes (2400 sec) and they will receive platelet transfusion in the amount of 1 apheresis unit when MA was below 30 mm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care (SOC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the SOC group, patients will receive PCC at the dose of 10 IE /kg of ideal body weight when the PT is below 50% and/or INR&gt;1.8 and/or received platelet transfusion in the amount of 1 apheresis when platelet count is below 50 G/L</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>thrombelastogram</intervention_name>
    <description>Patients in the TEG group will receive prothrombin complex concentrates (PCC) at a dose of 10 IE/kg of ideal body weight, when R-time was greater than 40 minutes (2400 sec) and they will receive platelet transfusion in the amount of 1 apheresis unit when MA was below 30 mm</description>
    <arm_group_label>Thrombelastogram (TEG)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>standard of care</intervention_name>
    <description>2) In the SOC group, patients will receive PCC at the dose of 10 IE /kg of ideal body weight when the PT is below 50% and/or INR&gt;1.8 and/or received platelet transfusion in the amount of 1 apheresis when platelet count is below 50 G/L</description>
    <arm_group_label>Standard of Care (SOC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        inclusion criteria&#xD;
&#xD;
          -  Liver cirrhosis&#xD;
&#xD;
          -  &gt;18 years&#xD;
&#xD;
          -  Indication for TIPS implantation&#xD;
&#xD;
          -  Ability to sign informed consent exclusion criteria&#xD;
&#xD;
          -  Contraindications against TIPS implantation&#xD;
&#xD;
          -  Hepatocellular carcinoma BCLC D&#xD;
&#xD;
          -  Ongoing bleeding&#xD;
&#xD;
          -  pre-existing anticoagulant therapy at time of inclusion&#xD;
&#xD;
          -  administration of blood products within 1 week prior to the enrolment&#xD;
&#xD;
          -  Other malignancies that lead to an impaired 90-day survival&#xD;
&#xD;
          -  Inherit blood clotting disorders&#xD;
&#xD;
          -  Hepatic encephalopathy grade 3 or 4&#xD;
&#xD;
          -  any other condition or circumstance, which, in the opinion of the investigator, would&#xD;
             affect the patient's ability to participate in the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Internal Medicine, Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <zip>8010</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vanessa Stadlbauer, MD</last_name>
      <phone>0043316385</phone>
      <phone_ext>82282</phone_ext>
      <email>vanessa.stadlbauer@medunigraz.at</email>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</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>
  </condition_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/NCT04421924
org study id: TIPS-prospective
nct id: NCT04421924
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Assess whether a pre-interventional thrombelastography guided algorithm for assessing and
      correction of coagulation status in cirrhotic patients is safe and effective
Transjugular intrahepatic portosystemic shunt (TIPS) is a very effective procedure to treat
      complications of portal hypertension in liver cirrhosis. TIPS implantation is indicated in
      cirrhotic patients to treat or prevent portal hypertensive bleeding and to treat refractory
      ascites.

      During this procedure an artificial connection between portal vein and hepatic vein is placed
      via an image-guided endovascular approach. Although the procedure is very effective and
      reasonably safe, several complications can occur.

      Due to the underlying cirrhosis, morbidity and mortality of TIPS is high, with a 30-day
      mortality between 7 and 20%. Procedural site complications (transhepatic and transvenous
      access), bleeding, development of hepatic encephalopathy or other organ complications and
      stent complications comprise a considerable risk to the patients, however, the improvement of
      mortality, renal function and liver function outweighs the risks of the procedure. Optimal
      patient selection and preoperative preparation is crucial to avoid complications of this
      procedure.

      In liver cirrhosis, coagulation disturbances are common. In hepatic insufficiency, a balanced
      reduction in the levels of most of pro- and anticoagulant proteins produced in the liver does
      not impair thrombin generation until levels are quite low. However, the ability of the
      coagulation system to tolerate or recover from an insult is markedly impaired in liver
      disease. This allows the coagulation system to be more easily tipped into a state favouring
      either haemorrhage or thrombosis. The American Gastroenterology Association has recently
      published best practice advices to manage coagulation in cirrhosis. This review concludes
      that commonly used global coagulation tests are not optimal to assess the risk of bleeding in
      cirrhosis. A randomized controlled trial showed, that the use of thrombelastography (TEG) to
      assess coagulation in cirrhosis resulted in a significantly lower usage of blood products
      with no increase in bleeding rates.

      The bleeding risk for TIPS implantation is not well studied, ranging from 0.6-4.3% of fatal
      bleeding complications in older uncontrolled case series. No evidenced-based recommendations
      exist for the correction of coagulation abnormalities before TIPS - and the few existing
      recommendations are not backed with evidence but rather "eminence based". Currently, global
      tests of coagulation (prothrombin time and platelet count) are used to guide coagulation
      correction. Mostly, cut-offs without sufficient evidence (PT >50%/ INR >1.8 and platelets >50
      G/L) are used for correction of coagulation.

      Also, the risk of stent thrombosis needs to be considered, therefore "blind" substitution of
      clotting factors or platelet transfusions is not advisable. Unfortunately, the study by De
      Pietri et al. (6) did only include one patient undergoing TIPS (in the standard of care (SOC)
      arm), therefore it is yet unknown, whether TEG is useful for guiding the correction of
      coagulation abnormalities in cirrhosis.

      The aim of this trial is to assess, whether TEG guided pre-interventional assessment and
      correction of coagulation in cirrhotic patients is safe and effective

      The study will be performed as a single-center, open-label, randomized prospective cohort
      study
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: blood product requirement
time frame: 2 days
description: Amount of blood products (coagulation factors and platelet transfusions) transfused for pre-interventional correction of coagulation status
measure: Bleeding
time frame: 90 days
description: Rate of bleeding complications (BARC criteria)
measure: complications
time frame: 90 days
description: Rate of transfusion related complications
measure: Mortality
time frame: 90 days
description: Mortality rate
measure: Modified TIPS Score (MOTS)
time frame: 90 days
description: Predictive power of modified TIPS score (MOTS) using the routine parameter, bilirubin, urea and INR; values range from 0-3, high score means worse outcome
measure: Factor XIII
time frame: 2 days
description: Comparison of measured FXIII activity levels with TEG parameters (alpha-angle, K-time, MA) for assessing feasibility of TEG in predicting deficiency of FXIII activity in these specific group of patients.
arm group label: Thrombelastogram (TEG)
arm group type: Experimental
description: Patients in the TEG group will receive prothrombin complex concentrates (PCC) at a dose of 10 IE/kg of ideal body weight, when R-time was greater than 40 minutes (2400 sec) and they will receive platelet transfusion in the amount of 1 apheresis unit when MA was below 30 mm.
arm group label: Standard of Care (SOC)
arm group type: Experimental
description: In the SOC group, patients will receive PCC at the dose of 10 IE /kg of ideal body weight when the PT is below 50% and/or INR>1.8 and/or received platelet transfusion in the amount of 1 apheresis when platelet count is below 50 G/L
intervention type: Procedure
intervention name: thrombelastogram
description: Patients in the TEG group will receive prothrombin complex concentrates (PCC) at a dose of 10 IE/kg of ideal body weight, when R-time was greater than 40 minutes (2400 sec) and they will receive platelet transfusion in the amount of 1 apheresis unit when MA was below 30 mm
arm group label: Thrombelastogram (TEG)
intervention type: Procedure
intervention name: standard of care
description: 2) In the SOC group, patients will receive PCC at the dose of 10 IE /kg of ideal body weight when the PT is below 50% and/or INR>1.8 and/or received platelet transfusion in the amount of 1 apheresis when platelet count is below 50 G/L
arm group label: Standard of Care (SOC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: Austria
responsible party type: Sponsor
mesh term: Liver Cirrhosis
sharing ipd: No