xml: <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/NCT06021184</url>
    </required_header>
    <id_info>
      <org_study_id>ADEFES</org_study_id>
      <nct_id>NCT06021184</nct_id>
    </id_info>
    <brief_title>&quot;ADE Fibrinogen/RBC&quot; Ratio on Mortality and Outcome in Massive Transfusion Patients</brief_title>
    <acronym>ADEFES</acronym>
    <official_title>The Impact of &quot;ADE Fibrinogen/RBC&quot; Ratio on Mortality and Outcome in Massive Transfusion Patients: ADEFES TRIAL</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sakarya University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sakarya University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary aim of this study is to retro- and prospectively determine the effects of the&#xD;
        ratio of total fibrinogen amount to erythrocyte suspension (ACE Fibrinogen/RBC) on 30-day&#xD;
        mortality over the approximate equivalent dose given during massive transfusion.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Massive transfusion, defined as the transfusion of total body blood volume (10 units of&#xD;
        erythrocyte suspension) or more within 24 hours, remains one of the greatest challenges for&#xD;
        the anesthetist. Despite all the medical advances, in cardiac surgery, obstetric surgery,&#xD;
        trauma-orthopedic surgery, major gastrointestinal-genitor-urinary system surgeries, which are&#xD;
        among the major bleeding surgeries, massive hemorrhage continues to be an important mortality&#xD;
        and morbidity factor. In addition to major surgeries with known expected bleeding, massive&#xD;
        transfusion requirement may arise with any undesirable intraoperative event. While the&#xD;
        process is easier to manage with proper preparation and an organized procedure in expected&#xD;
        bleeding, a chaotic response may be encountered in unexpected situations. Special protocols&#xD;
        for each division have been developed by clinicians to manage this critical process, and work&#xD;
        continues on these protocols to improve the outcome.&#xD;
  &#xD;
        Massive bleeding management mainly focuses on transfusion and fluid resuscitation. Regardless&#xD;
        of the situation requiring massive transfusion, the goals of treatment in massive bleeding&#xD;
        are to maintain organ perfusion pressure and oxygen delivery, immediately stop bleeding and&#xD;
        coagulopathy. While these goals can be achieved through resuscitation with blood products and&#xD;
        surgical intervention, the triad of hypothermia, acidosis, and coagulopathy that occurs with&#xD;
        the process contributes to increased morbidity and mortality in such scenarios.&#xD;
  &#xD;
        The literature on major bleeding from trauma has highlighted some issues contributed to&#xD;
        improved clinical outcomes such as, damage-controlled resuscitation, including timely&#xD;
        initiation of transfusion, early use of clotting factors, minimizing the use of crystalloids.&#xD;
        The landmark PROPPR study found that in the resuscitation of trauma patients, a 1:1:1 ratio&#xD;
        of FFP:platelet:RBC transfusion during massive bleeding resulted in hemostasis in a greater&#xD;
        number of patients (86% versus 78%) compared to a 1:1:2 ratio, additionally, they found fewer&#xD;
        deaths from bleeding within 24 hours (14.6% versus 9.2%). However, no significant difference&#xD;
        was found in 24-hour or 30-day overall mortality. In a systematic review evaluating&#xD;
        retrospective data on transfusions for obstetric bleeding, it was shown that the amount of&#xD;
        FFP administered was greater than the amount of RBC. Since the mortality rate from massive&#xD;
        obstetric hemorrhage is lower than that of traumatic hemorrhage, it is difficult to&#xD;
        prospectively evaluate the effects of massive transfusion. This review recommends a FFP/RBC&#xD;
        ratio of ≥1, with the results of all retrospective studies described on transfusions for&#xD;
        obstetric hemorrhage. Studies in cardiac surgery also suggest that higher rates of FFP/RBC&#xD;
        transfusion are associated with better outcomes in patients with massive bleeding.&#xD;
  &#xD;
        In general, the high ratio of transfused FFP to RBC in bleeding surgeries requiring massive&#xD;
        transfusion has been associated with positive results. FFP contains all coagulation factors&#xD;
        and fibrinogen, as well as restoring the volume deficit that occurs with major bleeding,&#xD;
        which reduces the crystalloid requirement and prevents extra dilution of coagulation factors.&#xD;
        Fibrinogen is the clotting factor whose level drops the fastest during bleeding. Fibrinogen&#xD;
        is a unique coagulation building block that plays a role in both primary and secondary&#xD;
        hemostasis. Based on the results of the RETIC trial, the effectiveness of fibrinogen&#xD;
        supplementation in limiting blood loss appears to be strongly dependent on timing of&#xD;
        fibrinogen administration and increasing levels above 200 mg·dL-1. The 5th Edition of the&#xD;
        European Guidelines for the Management of Major Posttraumatic Hemorrhage and Coagulopathy&#xD;
        recommends early and repeated monitoring of fibrinogen concentrations and/or polymerization&#xD;
        and rapid correction of deficiencies. Accordingly, 3-4 g of fibrinogen concentrate or 15-20&#xD;
        units of cryoprecipitate is recommended as an initial dose in massive bleeding. While RETIC&#xD;
        stands out as a randomized controlled prospective study on the role of fibrinogen in massive&#xD;
        transfusion in trauma patients, there are few cardiac and transplantation surgery studies in&#xD;
        various types of research. Regardless of the cause, early restoration of fibrinogen levels in&#xD;
        case of massive bleeding reduces transfusion requirement by preventing ongoing bleeding.&#xD;
        Ideally, fibrinogen concentrate and/or cryoprecipitate are used in fibrinogen replacement,&#xD;
        and FFP is used as a weaker fibrinogen source. During massive transfusion, repeated doses of&#xD;
        FFP/cryoprecipitate/fibrinogen concentrate are used. All of these blood products have&#xD;
        different amounts of fibrinogen content. In many previous studies, the formula for improving&#xD;
        the results was investigated by looking at transfusion rates such as FFP/RBC, RBC/platelet,&#xD;
        FFP/RBC/Platelet. In the light of this information, our hypothesis is that mortality can be&#xD;
        reduced with a high rate of total fibrinogen transfusion from various sources. The primary&#xD;
        aim of our study is to retro- and prospectively determine the effects of the ratio of total&#xD;
        fibrinogen amount to erythrocyte suspension (ACE Fibrinogen/RBC) on 30-day mortality over the&#xD;
        approximate equivalent dose given during massive transfusion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 18, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2025</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Other</time_perspective>
    </study_design_info>
    <target_duration>30 Days</target_duration>
    <primary_outcome>
      <measure>Mortality within the first 30 days of follow-up.</measure>
      <time_frame>30-day survival after massive transfusion</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Survival</measure>
      <time_frame>24-hour mortality</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Survival</measure>
      <time_frame>3-month mortality</time_frame>
    </secondary_outcome>
    <enrollment type="Anticipated">920</enrollment>
    <condition>Massive Transfusion</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Adult patients who received massive transfusion&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥ 18&#xD;
  &#xD;
            2. Surgical patients who received ≥ 4 U RBC transfusions within 24 hours&#xD;
  &#xD;
                 -  5 U RBC transfusion within 4 h&#xD;
  &#xD;
                 -  4 U RBC transfusion within 1 h Bleeding in excess of 1.5 mL/kg/min, over 20 min&#xD;
  &#xD;
            3. Elective or emergency surgical procedures with major bleeding. Major bleeding&#xD;
               surgeries; cardiovascular surgery, obstetric surgery, orthopedics/trauma surgery and&#xD;
               major GIS-GUS surgeries&#xD;
  &#xD;
            4. Informed Consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Death before massive transfusion&#xD;
  &#xD;
            2. Death during massive transfusion&#xD;
  &#xD;
            3. Patients whose perioperative bleeding and transfusion data cannot be accessed in&#xD;
               detail&#xD;
  &#xD;
            4. Patients with missing data or non-compliance with study protocol&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <overall_contact>
      <last_name>Aslı Demir, Prof</last_name>
      <phone>+905052491598</phone>
      <email>zaslidem@yahoo.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Fatma Kavak Akelma, Assoc Prof</last_name>
      <phone>+905327079113</phone>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sakarya University</investigator_affiliation>
      <investigator_full_name>Burçin Çakır</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <keyword>massive transfusion</keyword>
    <keyword>fibrinogen</keyword>
    <keyword>fresh frozen plasma</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06021184
  org study id: ADEFES
  nct id: NCT06021184
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The primary aim of this study is to retro- and prospectively determine the effects of the
        ratio of total fibrinogen amount to erythrocyte suspension (ACE Fibrinogen/RBC) on 30-day
        mortality over the approximate equivalent dose given during massive transfusion.
  Massive transfusion, defined as the transfusion of total body blood volume (10 units of
        erythrocyte suspension) or more within 24 hours, remains one of the greatest challenges for
        the anesthetist. Despite all the medical advances, in cardiac surgery, obstetric surgery,
        trauma-orthopedic surgery, major gastrointestinal-genitor-urinary system surgeries, which are
        among the major bleeding surgeries, massive hemorrhage continues to be an important mortality
        and morbidity factor. In addition to major surgeries with known expected bleeding, massive
        transfusion requirement may arise with any undesirable intraoperative event. While the
        process is easier to manage with proper preparation and an organized procedure in expected
        bleeding, a chaotic response may be encountered in unexpected situations. Special protocols
        for each division have been developed by clinicians to manage this critical process, and work
        continues on these protocols to improve the outcome.
  
        Massive bleeding management mainly focuses on transfusion and fluid resuscitation. Regardless
        of the situation requiring massive transfusion, the goals of treatment in massive bleeding
        are to maintain organ perfusion pressure and oxygen delivery, immediately stop bleeding and
        coagulopathy. While these goals can be achieved through resuscitation with blood products and
        surgical intervention, the triad of hypothermia, acidosis, and coagulopathy that occurs with
        the process contributes to increased morbidity and mortality in such scenarios.
  
        The literature on major bleeding from trauma has highlighted some issues contributed to
        improved clinical outcomes such as, damage-controlled resuscitation, including timely
        initiation of transfusion, early use of clotting factors, minimizing the use of crystalloids.
        The landmark PROPPR study found that in the resuscitation of trauma patients, a 1:1:1 ratio
        of FFP:platelet:RBC transfusion during massive bleeding resulted in hemostasis in a greater
        number of patients (86% versus 78%) compared to a 1:1:2 ratio, additionally, they found fewer
        deaths from bleeding within 24 hours (14.6% versus 9.2%). However, no significant difference
        was found in 24-hour or 30-day overall mortality. In a systematic review evaluating
        retrospective data on transfusions for obstetric bleeding, it was shown that the amount of
        FFP administered was greater than the amount of RBC. Since the mortality rate from massive
        obstetric hemorrhage is lower than that of traumatic hemorrhage, it is difficult to
        prospectively evaluate the effects of massive transfusion. This review recommends a FFP/RBC
        ratio of ≥1, with the results of all retrospective studies described on transfusions for
        obstetric hemorrhage. Studies in cardiac surgery also suggest that higher rates of FFP/RBC
        transfusion are associated with better outcomes in patients with massive bleeding.
  
        In general, the high ratio of transfused FFP to RBC in bleeding surgeries requiring massive
        transfusion has been associated with positive results. FFP contains all coagulation factors
        and fibrinogen, as well as restoring the volume deficit that occurs with major bleeding,
        which reduces the crystalloid requirement and prevents extra dilution of coagulation factors.
        Fibrinogen is the clotting factor whose level drops the fastest during bleeding. Fibrinogen
        is a unique coagulation building block that plays a role in both primary and secondary
        hemostasis. Based on the results of the RETIC trial, the effectiveness of fibrinogen
        supplementation in limiting blood loss appears to be strongly dependent on timing of
        fibrinogen administration and increasing levels above 200 mg·dL-1. The 5th Edition of the
        European Guidelines for the Management of Major Posttraumatic Hemorrhage and Coagulopathy
        recommends early and repeated monitoring of fibrinogen concentrations and/or polymerization
        and rapid correction of deficiencies. Accordingly, 3-4 g of fibrinogen concentrate or 15-20
        units of cryoprecipitate is recommended as an initial dose in massive bleeding. While RETIC
        stands out as a randomized controlled prospective study on the role of fibrinogen in massive
        transfusion in trauma patients, there are few cardiac and transplantation surgery studies in
        various types of research. Regardless of the cause, early restoration of fibrinogen levels in
        case of massive bleeding reduces transfusion requirement by preventing ongoing bleeding.
        Ideally, fibrinogen concentrate and/or cryoprecipitate are used in fibrinogen replacement,
        and FFP is used as a weaker fibrinogen source. During massive transfusion, repeated doses of
        FFP/cryoprecipitate/fibrinogen concentrate are used. All of these blood products have
        different amounts of fibrinogen content. In many previous studies, the formula for improving
        the results was investigated by looking at transfusion rates such as FFP/RBC, RBC/platelet,
        FFP/RBC/Platelet. In the light of this information, our hypothesis is that mortality can be
        reduced with a high rate of total fibrinogen transfusion from various sources. The primary
        aim of our study is to retro- and prospectively determine the effects of the ratio of total
        fibrinogen amount to erythrocyte suspension (ACE Fibrinogen/RBC) on 30-day mortality over the
        approximate equivalent dose given during massive transfusion.
  observational model: Cohort
  time perspective: Other
  measure: Mortality within the first 30 days of follow-up.
  time frame: 30-day survival after massive transfusion
  measure: Survival
  time frame: 24-hour mortality
  measure: Survival
  time frame: 3-month mortality
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  last name: Aslı Demir, Prof
  phone: +905052491598
  email: zaslidem@yahoo.com
  last name: Fatma Kavak Akelma, Assoc Prof
  phone: +905327079113
  responsible party type: Principal Investigator
  investigator affiliation: Sakarya University
  investigator full name: Burçin Çakır
  investigator title: Associate Professor
  sharing ipd: No