<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/NCT04405518</url>
  </required_header>
  <id_info>
    <org_study_id>TROMBOFIBtrial</org_study_id>
    <secondary_id>2018-002510-13</secondary_id>
    <nct_id>NCT04405518</nct_id>
  </id_info>
  <brief_title>Impact of Two Guided Transfusion Strategies on Blood Product Requirements in Liver Transplantation.</brief_title>
  <official_title>Impact of Two Thromboelastometry-guided Transfusion Strategies on Blood Product Requirements in Liver Transplantation. a Multicenter, Randomized Trial. TROMBOFIBtrial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Antoni Sabaté Pes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Universitari de Bellvitge</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is a national multicentre clinical study, where 3 hospitals are involved: Bellvitge&#xD;
      University Hospital, Clinic Hospital of Barcelona and Cruces Hospital of Bilbao). It is a&#xD;
      randomized study based on the Hemoglobin value of the patient with a 1:1 ratio, parallel&#xD;
      groups, controlled and single blind, in patients undergoing an orthotopic liver transplant,&#xD;
      confirming previously that the participants fulfill all the inclusion criteria and none of&#xD;
      exclusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 176 patients will be included (88 per group) and each center can not include more&#xD;
      than 40% of the sample to avoid bias.&#xD;
&#xD;
      Blood samples will be analyzed at different times of the surgical intervention by an&#xD;
      electronic device called thromboelastogram. It evaluates the blood clot characteristics and,&#xD;
      depending on the results, assesses the need to correct values by the administration of&#xD;
      fibrinogen or platelets.&#xD;
&#xD;
      One of the coagulation parameter evaluated and corrected by thromboelastogram is called&#xD;
      A10FIBTEM. In a previous study, the investigators have seen that maintaining some specific&#xD;
      ranges in the A10FIBTEM, results in a decrease of the use of blood products. That's why the&#xD;
      investigators have created 2 groups:&#xD;
&#xD;
        -  The control group will be corrected up to a value of A10FIBTEM = 8mm.&#xD;
&#xD;
        -  The intervention group will be corrected up to a value of A10FIBTEM = 11mm.&#xD;
&#xD;
      Subsequently, results between groups will be compared. The investigators have to consider&#xD;
      that the drug used in this study (Riastap) is an authorized and commercial drug.&#xD;
&#xD;
      The main objective is to demonstrate that the administration of fibrinogen in the&#xD;
      intervention group compared to the control group changes the administration of red blood&#xD;
      cells pack during the liver transplant and in the first 24 hours after.&#xD;
&#xD;
      Secondary objectives consist in demonstrate that in the intervention group, there is also a&#xD;
      change in the administration of other blood products, a change in acute renal damage, a&#xD;
      change in hours of mechanical ventilation, no changes in thrombotic events in the hepatic&#xD;
      graft or in the patient in the first 90 days of the liver transplant and no changes in re&#xD;
      operations, re-transplantation, or mortality during the first 90 days of the liver&#xD;
      transplant, compared to the control group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 17, 2019</start_date>
  <completion_date type="Anticipated">October 31, 2022</completion_date>
  <primary_completion_date type="Actual">November 2, 2021</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>
    <intervention_model_description>Participants will be randomly divided into a group receiving concentrate of fibrinogen in the different phases of the liver transplant procedure, to achieve&#xD;
Thromboelastometry value (A10 FIBTEM) of 11mm (study group) or&#xD;
Thromboelastometry value (A10 FIBTEM) of 8mm (control group) The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of the rate of red blood cell packs transfusion during procedure and in the first 24hours after between groups.</measure>
    <time_frame>Intraoperative and the first 24 hours after surgery.</time_frame>
    <description>Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10FIBTEM value of 11mm, change the administration of red blood cell pack during the procedure and in the first 24 hours after it, comparing to the administration of fibrinogen up to an A10FIBTEM of 8mm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the rate of other blood products between groups.</measure>
    <time_frame>Intraoperative and the first 24 hours after surgery.</time_frame>
    <description>Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the administration of platelets, frozen fresh plasma and other blood products.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the acute kidney injury between groups using the Kidney Disease Improving Global Outcomes scale,the minimum values is 1 and the maximum values is 3, higher scores mean a worse outcome.</measure>
    <time_frame>first week after the procedure and until 90 days after the procedure.</time_frame>
    <description>Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the kidney injury through study completion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the duration of mechanical ventilation in hours between groups.</measure>
    <time_frame>first week after the procedure and until 90 days after the procedure..</time_frame>
    <description>Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the need of mechanical ventilation through study completion (comparing the number of hours of mechanical ventilation of each group).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with major advers cardiac events (MACE), Number of participants with, any sign of infection, Number of participants with neurological events through study completion</measure>
    <time_frame>Until 90 days after the procedure.</time_frame>
    <description>Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the Number of participants with any adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with thrombotic events in the hepatic graft measured by ecodoppler assessment; and the number of participants with any other thrombotic events measured by ecodoppler assessment of leg extremity or tomography axial of the lungs</measure>
    <time_frame>Until 90 days after procedure</time_frame>
    <description>Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm do not change thrombotic events in the hepatic graft or in the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who require reoperation for any cause; Number of participants who require being re transplanted and number of participant who died through the study completion</measure>
    <time_frame>Until 90 days after procedure</time_frame>
    <description>Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm do not change the outcome related to reoperation, re-transplantations or mortality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">188</enrollment>
  <condition>Fibrin Blood Clot</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy.&#xD;
Formula: 8mm - A10FIBTEM registered in mm) x 1.1 = fibrinogen dose required</description>
  </arm_group>
  <arm_group>
    <arm_group_label>intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy.&#xD;
Formula: 11mm - A10FIBTEM registered in mm) x 1.1 = fibrinogen dose required</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fibrinogen Concentrate (Human) 1 MG [RiaSTAP]</intervention_name>
    <description>The drug used in this study is Riastap, 1g (Fibrinogen). The dose administered will depend on the arm group assigned and in the results of the thromboelastogram during the procedure.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>intervention group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years.&#xD;
&#xD;
          -  Candidate to an orthotopic liver trasnplantation.&#xD;
&#xD;
          -  Informed consent.&#xD;
&#xD;
          -  Preoperative hemoglobine &lt;/= 130 g/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Preoperative hemoglobin&gt; 130 g / L&#xD;
&#xD;
          -  Familial amyloid polyneuropathy&#xD;
&#xD;
          -  Polycystosis hepatic&#xD;
&#xD;
          -  Living donor liver transplant&#xD;
&#xD;
          -  Uncontrolled donor after cardiac death&#xD;
&#xD;
          -  Acute / subacute liver failure&#xD;
&#xD;
          -  Re-transplant (in the same hospital admission)&#xD;
&#xD;
          -  Use of Anticoagulation drugs before transplantation.&#xD;
&#xD;
          -  Age &lt;18 years.&#xD;
&#xD;
          -  Pregnancy and lactation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marta Caballero</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bellvitge University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Josep Beltran</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinic Hospital, Barcelona</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rosa Gutierrez</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cruces Hospital, Bilbao</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bellvitge Universitary Hospital</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <state>Barcelone</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cruces Hospital</name>
      <address>
        <city>Bilbao</city>
        <state>Vizcaya</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinic Hospital</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>October 10, 2019</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>November 24, 2021</last_update_submitted>
  <last_update_submitted_qc>November 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitari de Bellvitge</investigator_affiliation>
    <investigator_full_name>Antoni Sabaté Pes</investigator_full_name>
    <investigator_title>Head of Anesthesiology and Reanimation Department; MD; PhD</investigator_title>
  </responsible_party>
  <keyword>fibrinogen</keyword>
  <keyword>red blood cell pack transfusion</keyword>
  <keyword>orthotopic liver transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 9, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04405518
org study id: TROMBOFIBtrial
secondary id: 2018-002510-13
nct id: NCT04405518
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
It is a national multicentre clinical study, where 3 hospitals are involved: Bellvitge
      University Hospital, Clinic Hospital of Barcelona and Cruces Hospital of Bilbao). It is a
      randomized study based on the Hemoglobin value of the patient with a 1:1 ratio, parallel
      groups, controlled and single blind, in patients undergoing an orthotopic liver transplant,
      confirming previously that the participants fulfill all the inclusion criteria and none of
      exclusion.
A total of 176 patients will be included (88 per group) and each center can not include more
      than 40% of the sample to avoid bias.

      Blood samples will be analyzed at different times of the surgical intervention by an
      electronic device called thromboelastogram. It evaluates the blood clot characteristics and,
      depending on the results, assesses the need to correct values by the administration of
      fibrinogen or platelets.

      One of the coagulation parameter evaluated and corrected by thromboelastogram is called
      A10FIBTEM. In a previous study, the investigators have seen that maintaining some specific
      ranges in the A10FIBTEM, results in a decrease of the use of blood products. That's why the
      investigators have created 2 groups:

        -  The control group will be corrected up to a value of A10FIBTEM = 8mm.

        -  The intervention group will be corrected up to a value of A10FIBTEM = 11mm.

      Subsequently, results between groups will be compared. The investigators have to consider
      that the drug used in this study (Riastap) is an authorized and commercial drug.

      The main objective is to demonstrate that the administration of fibrinogen in the
      intervention group compared to the control group changes the administration of red blood
      cells pack during the liver transplant and in the first 24 hours after.

      Secondary objectives consist in demonstrate that in the intervention group, there is also a
      change in the administration of other blood products, a change in acute renal damage, a
      change in hours of mechanical ventilation, no changes in thrombotic events in the hepatic
      graft or in the patient in the first 90 days of the liver transplant and no changes in re
      operations, re-transplantation, or mortality during the first 90 days of the liver
      transplant, compared to the control group.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomly divided into a group receiving concentrate of fibrinogen in the different phases of the liver transplant procedure, to achieve
Thromboelastometry value (A10 FIBTEM) of 11mm (study group) or
Thromboelastometry value (A10 FIBTEM) of 8mm (control group) The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Evaluation of the rate of red blood cell packs transfusion during procedure and in the first 24hours after between groups.
time frame: Intraoperative and the first 24 hours after surgery.
description: Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10FIBTEM value of 11mm, change the administration of red blood cell pack during the procedure and in the first 24 hours after it, comparing to the administration of fibrinogen up to an A10FIBTEM of 8mm.
measure: Evaluation of the rate of other blood products between groups.
time frame: Intraoperative and the first 24 hours after surgery.
description: Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the administration of platelets, frozen fresh plasma and other blood products.
measure: Evaluation of the acute kidney injury between groups using the Kidney Disease Improving Global Outcomes scale,the minimum values is 1 and the maximum values is 3, higher scores mean a worse outcome.
time frame: first week after the procedure and until 90 days after the procedure.
description: Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the kidney injury through study completion
measure: Evaluation of the duration of mechanical ventilation in hours between groups.
time frame: first week after the procedure and until 90 days after the procedure..
description: Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the need of mechanical ventilation through study completion (comparing the number of hours of mechanical ventilation of each group).
measure: Number of participants with major advers cardiac events (MACE), Number of participants with, any sign of infection, Number of participants with neurological events through study completion
time frame: Until 90 days after the procedure.
description: Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the Number of participants with any adverse events.
measure: Number of participants with thrombotic events in the hepatic graft measured by ecodoppler assessment; and the number of participants with any other thrombotic events measured by ecodoppler assessment of leg extremity or tomography axial of the lungs
time frame: Until 90 days after procedure
description: Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm do not change thrombotic events in the hepatic graft or in the patient.
measure: Number of participants who require reoperation for any cause; Number of participants who require being re transplanted and number of participant who died through the study completion
time frame: Until 90 days after procedure
description: Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm do not change the outcome related to reoperation, re-transplantations or mortality.
arm group label: Control group
arm group type: Active Comparator
description: The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy.
Formula: 8mm - A10FIBTEM registered in mm) x 1.1 = fibrinogen dose required
arm group label: intervention group
arm group type: Experimental
description: The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy.
Formula: 11mm - A10FIBTEM registered in mm) x 1.1 = fibrinogen dose required
intervention type: Drug
intervention name: Fibrinogen Concentrate (Human) 1 MG [RiaSTAP]
description: The drug used in this study is Riastap, 1g (Fibrinogen). The dose administered will depend on the arm group assigned and in the results of the thromboelastogram during the procedure.
arm group label: Control group
arm group label: intervention group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Marta Caballero
role: Principal Investigator
affiliation: Bellvitge University Hospital
last name: Josep Beltran
role: Principal Investigator
affiliation: Clinic Hospital, Barcelona
last name: Rosa Gutierrez
role: Principal Investigator
affiliation: Cruces Hospital, Bilbao
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor-Investigator
investigator affiliation: Hospital Universitari de Bellvitge
investigator full name: Antoni Sabaté Pes
investigator title: Head of Anesthesiology and Reanimation Department; MD; PhD
mesh term: Thrombosis
sharing ipd: No
submitted: September 9, 2023