<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/NCT04472312</url>
  </required_header>
  <id_info>
    <org_study_id>20.121</org_study_id>
    <nct_id>NCT04472312</nct_id>
  </id_info>
  <brief_title>Portal Pressure Effects of Phlebotomy Combined to Vasopressin Use in Cirrhotic Patients Undergoing Liver Transplantation</brief_title>
  <acronym>PORTAL</acronym>
  <official_title>Portal Pressure Effects of Phlebotomy Combined to Vasopressin Use in Cirrhotic Patients Undergoing Liver Transplantation: the PORTAL Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre hospitalier de l'Université de Montréal (CHUM)</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>
      Liver transplantation is the standard treatment for chronic advanced liver disease, whether&#xD;
      or not associated with a primary liver tumor. The intraoperative bleeding and the need for&#xD;
      blood transfusion, encountered in this major surgery are associated with increased morbidity&#xD;
      and mortality. However, this hemorrhagic risk has been drastically reduced in the last 20&#xD;
      years and liver transplants without the use of blood products are now possible. Indeed,&#xD;
      improvements in medical and surgical techniques associated with a better understanding of the&#xD;
      pathophysiology of the cirrhotic patient have enabled this advance. One of the targeted&#xD;
      therapeutic strategies is the control of portal hypertension. Several treatments have been&#xD;
      sought, such as the use of splanchnic vasoconstrictors (such as vasopressin) and hypovolemic&#xD;
      phlebotomy. These techniques reduce portal pressure and seem to reduce intraoperative&#xD;
      bleeding with, even, a protective effect on kidney function. Their single-use or their&#xD;
      combination is currently used in certain centers of expertise in liver transplantation.&#xD;
      However, the hemodynamic effects of the combination of these 2 treatments on portal pressure&#xD;
      has never been demonstrated. In this study, the effect of vasopressin, combined with a&#xD;
      hypovolemic phlebotomy, on portal pressure in cirrhotic patients undergoing liver&#xD;
      transplantation will be evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      METHODS&#xD;
&#xD;
      Objectives&#xD;
&#xD;
      The primary objective will be to measure the hemodynamic effects of vasopressin on portal&#xD;
      pressure in cirrhotic patients who have had a hypovolemic phlebotomy during a liver&#xD;
      transplant.&#xD;
&#xD;
      The secondary objectives will be to measure the effects of vasopressin on portal pressure in&#xD;
      patients who have not had a phlebotomy and to compare this effect between patients who have&#xD;
      or have not had a hypovolemic phlebotomy.&#xD;
&#xD;
      The tertiary objective will be to assess the effect of the variation in portal pressure under&#xD;
      vasopressin, associated or not with a hypovolemic phlebotomy, on hemorrhagic clinical&#xD;
      outcomes (intraoperative bleeding and blood transfusions).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 24, 2020</start_date>
  <completion_date type="Actual">July 6, 2022</completion_date>
  <primary_completion_date type="Actual">June 29, 2022</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>Portal pressure measurement</measure>
    <time_frame>During the surgery (intraoperatively)</time_frame>
    <description>The venous pressure in the liver will be measured by inserting a very fine needle in the portal vein. The needle will be connected to a pressure sensor and will be removed after the measurement. This measure will be performed at three different moments during the surgery; 1) as soon as possible after the incision; 2) 5 minutes after the end of the hypovolemic phlebotomy (if performed); 3) 10 minutes after the start of vasopressin infusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intraoperative blood loss</measure>
    <time_frame>At the end of the surgery</time_frame>
    <description>During the liver transplantation, a cell salvage device (Cell Saver) will be set up in the operating room. As the surgery progresses, the blood lost by the patient will be collected using suctions. The volume of blood (mL) in the suctions will be measured at the end of the surgery, before the blood is cleaned and returned back to the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Packed red blood cell transfusion rates</measure>
    <time_frame>Intraoperatively and up to 24 hours following surgery</time_frame>
    <description>Number of units of packed red blood cells transfused to participants will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of acute kidney injury (AKI) grade 2 or 3</measure>
    <time_frame>Assessed at 24 hours and 48 hours following surgery</time_frame>
    <description>The onset or worsening of acute postoperative grade 2 or 3 renal failure according to KDIGO-AKI criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of new renal therapy replacement</measure>
    <time_frame>Postoperative setting up to 7 days following surgery</time_frame>
    <description>Any need of new renal therapy replacement occurring during the hospital stay up to 7 days following surgery will be recorded.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">60</enrollment>
  <condition>Liver Transplantation</condition>
  <condition>Portal Hypertension</condition>
  <condition>Blood Transfusion</condition>
  <condition>Blood Loss, Surgical</condition>
  <arm_group>
    <arm_group_label>Cirrhotic patients undergoing a liver transplantation</arm_group_label>
    <description>The investigators aim to conduct a prospective observational, non-interventional study including all cirrhotic patients undergoing a liver transplantation with a planned use of vasopressin during the surgery.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators aim to conduct a prospective observational, non-interventional study,&#xD;
        respecting current practice. This study will take place at the Centre de recherche de&#xD;
        l'Université de Montréal (CHUM) where there are approximately 70 to 80 liver transplants&#xD;
        per year.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cirrhotic patients undergoing a liver transplantation&#xD;
&#xD;
          -  18 years and older&#xD;
&#xD;
          -  Planned use of vasopressin during the surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fulminant or sub-fulminant hepatitis without underlying chronic liver disease&#xD;
&#xD;
          -  Anesthetic plan does not include the use of vasopressin (contraindication or not&#xD;
             relevant according to the anesthesiologist)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>François-Martin Carrier, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal (CHUM)</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>July 21, 2022</last_update_submitted>
  <last_update_submitted_qc>July 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 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>Hypertension, Portal</mesh_term>
    <mesh_term>Blood Loss, Surgical</mesh_term>
  </condition_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/NCT04472312
org study id: 20.121
nct id: NCT04472312
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Liver transplantation is the standard treatment for chronic advanced liver disease, whether
      or not associated with a primary liver tumor. The intraoperative bleeding and the need for
      blood transfusion, encountered in this major surgery are associated with increased morbidity
      and mortality. However, this hemorrhagic risk has been drastically reduced in the last 20
      years and liver transplants without the use of blood products are now possible. Indeed,
      improvements in medical and surgical techniques associated with a better understanding of the
      pathophysiology of the cirrhotic patient have enabled this advance. One of the targeted
      therapeutic strategies is the control of portal hypertension. Several treatments have been
      sought, such as the use of splanchnic vasoconstrictors (such as vasopressin) and hypovolemic
      phlebotomy. These techniques reduce portal pressure and seem to reduce intraoperative
      bleeding with, even, a protective effect on kidney function. Their single-use or their
      combination is currently used in certain centers of expertise in liver transplantation.
      However, the hemodynamic effects of the combination of these 2 treatments on portal pressure
      has never been demonstrated. In this study, the effect of vasopressin, combined with a
      hypovolemic phlebotomy, on portal pressure in cirrhotic patients undergoing liver
      transplantation will be evaluated.
METHODS

      Objectives

      The primary objective will be to measure the hemodynamic effects of vasopressin on portal
      pressure in cirrhotic patients who have had a hypovolemic phlebotomy during a liver
      transplant.

      The secondary objectives will be to measure the effects of vasopressin on portal pressure in
      patients who have not had a phlebotomy and to compare this effect between patients who have
      or have not had a hypovolemic phlebotomy.

      The tertiary objective will be to assess the effect of the variation in portal pressure under
      vasopressin, associated or not with a hypovolemic phlebotomy, on hemorrhagic clinical
      outcomes (intraoperative bleeding and blood transfusions).
observational model: Cohort
time perspective: Prospective
measure: Portal pressure measurement
time frame: During the surgery (intraoperatively)
description: The venous pressure in the liver will be measured by inserting a very fine needle in the portal vein. The needle will be connected to a pressure sensor and will be removed after the measurement. This measure will be performed at three different moments during the surgery; 1) as soon as possible after the incision; 2) 5 minutes after the end of the hypovolemic phlebotomy (if performed); 3) 10 minutes after the start of vasopressin infusion.
measure: Intraoperative blood loss
time frame: At the end of the surgery
description: During the liver transplantation, a cell salvage device (Cell Saver) will be set up in the operating room. As the surgery progresses, the blood lost by the patient will be collected using suctions. The volume of blood (mL) in the suctions will be measured at the end of the surgery, before the blood is cleaned and returned back to the patient.
measure: Packed red blood cell transfusion rates
time frame: Intraoperatively and up to 24 hours following surgery
description: Number of units of packed red blood cells transfused to participants will be recorded.
measure: Rate of acute kidney injury (AKI) grade 2 or 3
time frame: Assessed at 24 hours and 48 hours following surgery
description: The onset or worsening of acute postoperative grade 2 or 3 renal failure according to KDIGO-AKI criteria.
measure: Rate of new renal therapy replacement
time frame: Postoperative setting up to 7 days following surgery
description: Any need of new renal therapy replacement occurring during the hospital stay up to 7 days following surgery will be recorded.
arm group label: Cirrhotic patients undergoing a liver transplantation
description: The investigators aim to conduct a prospective observational, non-interventional study including all cirrhotic patients undergoing a liver transplantation with a planned use of vasopressin during the surgery.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: François-Martin Carrier, MD, FRCPC
role: Principal Investigator
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Hypertension, Portal
mesh term: Blood Loss, Surgical
sharing ipd: Undecided