<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/NCT03014700</url>
  </required_header>
  <id_info>
    <org_study_id>36374</org_study_id>
    <nct_id>NCT03014700</nct_id>
  </id_info>
  <brief_title>Fibrinogen Concentrate vs Cryoprecipitate</brief_title>
  <official_title>Repurposing of Fibrinogen Concentrate as a Cost-Effective and Safe Hemostatic Agent in Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      One of the most common hemostatic derangements in pediatric open- heart surgery is an acute&#xD;
      acquired hypofibrinogenemia. This compromises fibrin clot generation and platelet&#xD;
      aggregation, resulting in increased bleeding and allogenic blood transfusions.&#xD;
&#xD;
      Currently, fresh frozen plasma and cryoprecipitate are used to supplement fibrinogen in&#xD;
      pediatric cardiac patients. We propose that replacing cryoprecipitate with fibrinogen&#xD;
      concentrate will be as effective in treating post-CPB bleeding and will decrease total blood&#xD;
      product exposure when used as part of a blood transfusion algorithm.&#xD;
&#xD;
      We plan to include all patients undergoing cardiac surgery on CPB less than 12 months and a&#xD;
      fibrinogen level &lt;250mg/dL while on bypass.&#xD;
&#xD;
      We hope to demonstrate that fibrinogen concentrate is at least as effective as the standard&#xD;
      of care in the management of peri- operative bleeding in neonatal patients undergoing&#xD;
      cardiopulmonary bypass. If we are able to demonstrate that fibrinogen is at least as&#xD;
      effective as the standard of care, then we would plan a multi-center trial to demonstrate the&#xD;
      safety and efficacy of this medication. If we are able to demonstrate that fibrinogen&#xD;
      concentrate is effective, fibrinogen concentrate could replace allogenic products and&#xD;
      potentially decrease transfusion related morbidity in mortality in this population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients under 12 months of age requiring cardiopulmonary bypass surgery will be approached&#xD;
      for the study. Patients with a pre- existing coagulopathy, including unexplained bleeding or&#xD;
      history of clotting, will be excluded. Prior to the study beginning, patients will be&#xD;
      randomized to our standard transfusion algorithm with cryoprecipitate or fibrinogen&#xD;
      concentrate. As is standard of care, laboratory tests will be sent at standard times points&#xD;
&#xD;
        1. after the induction of anesthesia,&#xD;
&#xD;
        2. after initiation of bypass,&#xD;
&#xD;
        3. after separation from bypass and administration of protamine, and transfusion of either&#xD;
           fibrinogen concentrate or cryoprecipitate&#xD;
&#xD;
        4. on arrival to the ICU. These laboratory tests include hematocrit, arterial blood gas,&#xD;
           chemistry, thromboelastogram (TEG) and fibrinogen. Additional laboratory tests will be&#xD;
           sent as indicated by the clinical scenario to determine transfusion requirements. For&#xD;
           patients enrolled in the study, we will standardize the anesthetic management,&#xD;
           cardiopulmonary bypass protocol, and transfusion thresholds in the operating room and&#xD;
           ICU. We will collect demographic data, intraop and post-op laboratory values, bypass&#xD;
           times, intraop and post op transfusion data, chest tube output, adverse events, and&#xD;
           length of ventilation, ICU stay and hospital stay.&#xD;
&#xD;
      For patients randomized to the study arm (fibrinogen concentrate), the fibrinogen level&#xD;
      measured on bypass will be used to calculate the appropriate dose of fibrinogen concentrate&#xD;
      to achieve a level of 300mg/dL after separation from bypass. Fibrinogen concentrate will&#xD;
      replace cryoprecipitate in our post-operative transfusion algorithm. If the patient has&#xD;
      continued bleeding based on laboratory values and clinical situation, the patient will be&#xD;
      given cryoprecipitate as a rescue measure. Patients not on the study protocol will receive&#xD;
      our normal transfusion algorithm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2016</start_date>
  <completion_date type="Actual">April 25, 2018</completion_date>
  <primary_completion_date type="Actual">April 25, 2018</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival.</measure>
    <time_frame>From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours)</time_frame>
    <description>For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Chest Tube Output</measure>
    <time_frame>From administration end of surgery to 24 hours post operatively</time_frame>
    <description>Volume of chest tube drainage evaluated over first 24 hours post operatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hours of Mechanical Ventilation</measure>
    <time_frame>From administration of the drug during surgery to extubation in the ICU (up to 30 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay in Intensive Care Unit (ICU)</measure>
    <time_frame>From administration of the drug during surgery to discharge from the ICU (up to 3 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay in Hospital</measure>
    <time_frame>From administration of the drug during surgery to discharge from the hospital (up to 6 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Participants Who Died Within 30 Days Following Procedure</measure>
    <time_frame>From administration of the drug to 30 days following surgery</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Congenital Heart Disease</condition>
  <arm_group>
    <arm_group_label>Cryoprecipitate Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fibrinogen Concentrate Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fibrinogen Concentrate</intervention_name>
    <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
    <arm_group_label>Fibrinogen Concentrate Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cryoprecipitate</intervention_name>
    <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
    <arm_group_label>Cryoprecipitate Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Neonates of at least 32 weeks of gestational age and infants up to 12 months of age&#xD;
             with the diagnosis of congenital heart disease, requiring open heart surgery with&#xD;
             cardiopulmonary bypass&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing coagulopathy, including unexplained bleeding or history of clotting&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Glyn D Williams, MBChB, FFA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Laura Downey, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laura Downey</name>
      <address>
        <city>Emory</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <results_first_submitted>April 14, 2019</results_first_submitted>
  <results_first_submitted_qc>April 14, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 7, 2019</results_first_posted>
  <last_update_submitted>April 14, 2019</last_update_submitted>
  <last_update_submitted_qc>April 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Glyn David Williams</investigator_full_name>
    <investigator_title>Professor, Department of Anesthesiology, Perioperative and Pain Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 3, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03014700/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03014700/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cryoprecipitate Arm</title>
          <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
        </group>
        <group group_id="P2">
          <title>Fibrinogen Concentrate Arm</title>
          <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cryoprecipitate Arm</title>
          <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
        </group>
        <group group_id="B2">
          <title>Fibrinogen Concentrate Arm</title>
          <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4" lower_limit="2" upper_limit="5"/>
                    <measurement group_id="B2" value="4" lower_limit="2" upper_limit="7"/>
                    <measurement group_id="B3" value="4" lower_limit="2" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival.</title>
        <description>For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets.</description>
        <time_frame>From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cryoprecipitate Arm</title>
            <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
          </group>
          <group group_id="O2">
            <title>Fibrinogen Concentrate Arm</title>
            <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
          </group>
        </group_list>
        <measure>
          <title>Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival.</title>
          <description>For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets.</description>
          <units>ADT units</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="4" upper_limit="7"/>
                    <measurement group_id="O2" value="4" lower_limit="3" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Chest Tube Output</title>
        <description>Volume of chest tube drainage evaluated over first 24 hours post operatively</description>
        <time_frame>From administration end of surgery to 24 hours post operatively</time_frame>
        <population>Participants who completed the protocol are included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cryoprecipitate Arm</title>
            <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
          </group>
          <group group_id="O2">
            <title>Fibrinogen Concentrate Arm</title>
            <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
          </group>
        </group_list>
        <measure>
          <title>Chest Tube Output</title>
          <description>Volume of chest tube drainage evaluated over first 24 hours post operatively</description>
          <population>Participants who completed the protocol are included in the analysis</population>
          <units>ml/kg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.05" lower_limit="10.94" upper_limit="26.03"/>
                    <measurement group_id="O2" value="16.11" lower_limit="12.56" upper_limit="25.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hours of Mechanical Ventilation</title>
        <time_frame>From administration of the drug during surgery to extubation in the ICU (up to 30 days)</time_frame>
        <population>Participants who completed the protocol are included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cryoprecipitate Arm</title>
            <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
          </group>
          <group group_id="O2">
            <title>Fibrinogen Concentrate Arm</title>
            <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
          </group>
        </group_list>
        <measure>
          <title>Hours of Mechanical Ventilation</title>
          <population>Participants who completed the protocol are included in the analysis</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.32" lower_limit="18.68" upper_limit="98.73"/>
                    <measurement group_id="O2" value="27.10" lower_limit="20.42" upper_limit="51.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay in Intensive Care Unit (ICU)</title>
        <time_frame>From administration of the drug during surgery to discharge from the ICU (up to 3 months)</time_frame>
        <population>Participants who completed the protocol are included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cryoprecipitate Arm</title>
            <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
          </group>
          <group group_id="O2">
            <title>Fibrinogen Concentrate Arm</title>
            <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay in Intensive Care Unit (ICU)</title>
          <population>Participants who completed the protocol are included in the analysis</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.50" lower_limit="2.00" upper_limit="6.00"/>
                    <measurement group_id="O2" value="3.00" lower_limit="2.00" upper_limit="7.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay in Hospital</title>
        <time_frame>From administration of the drug during surgery to discharge from the hospital (up to 6 months)</time_frame>
        <population>Participants who completed the protocol are included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cryoprecipitate Arm</title>
            <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
          </group>
          <group group_id="O2">
            <title>Fibrinogen Concentrate Arm</title>
            <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay in Hospital</title>
          <population>Participants who completed the protocol are included in the analysis</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.00" lower_limit="5.00" upper_limit="19.00"/>
                    <measurement group_id="O2" value="7.00" lower_limit="4.00" upper_limit="11.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Participants Who Died Within 30 Days Following Procedure</title>
        <time_frame>From administration of the drug to 30 days following surgery</time_frame>
        <population>Participants who completed the protocol are included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cryoprecipitate Arm</title>
            <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
          </group>
          <group group_id="O2">
            <title>Fibrinogen Concentrate Arm</title>
            <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants Who Died Within 30 Days Following Procedure</title>
          <population>Participants who completed the protocol are included in the analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day of procedure through 30 days postoperatively or hospital discharge</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cryoprecipitate Arm</title>
          <description>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group&#xD;
Cryoprecipitate: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group</description>
        </group>
        <group group_id="E2">
          <title>Fibrinogen Concentrate Arm</title>
          <description>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group&#xD;
Fibrinogen Concentrate: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tamponade</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Stroke</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Exploration</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombosis requiring Intervention</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia requiring treatment</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection (with positive culture within 14 days)</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Repeat Surgery (less than 7 days)</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Glyn David Williams</name_or_title>
      <organization>Stanford university School of Medicine</organization>
      <phone>650-723-5728</phone>
      <email>jumbo@stanford.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03014700
org study id: 36374
nct id: NCT03014700
lead sponsor: 
collaborator: 
has dmc: Yes
One of the most common hemostatic derangements in pediatric open- heart surgery is an acute
      acquired hypofibrinogenemia. This compromises fibrin clot generation and platelet
      aggregation, resulting in increased bleeding and allogenic blood transfusions.

      Currently, fresh frozen plasma and cryoprecipitate are used to supplement fibrinogen in
      pediatric cardiac patients. We propose that replacing cryoprecipitate with fibrinogen
      concentrate will be as effective in treating post-CPB bleeding and will decrease total blood
      product exposure when used as part of a blood transfusion algorithm.

      We plan to include all patients undergoing cardiac surgery on CPB less than 12 months and a
      fibrinogen level <250mg/dL while on bypass.

      We hope to demonstrate that fibrinogen concentrate is at least as effective as the standard
      of care in the management of peri- operative bleeding in neonatal patients undergoing
      cardiopulmonary bypass. If we are able to demonstrate that fibrinogen is at least as
      effective as the standard of care, then we would plan a multi-center trial to demonstrate the
      safety and efficacy of this medication. If we are able to demonstrate that fibrinogen
      concentrate is effective, fibrinogen concentrate could replace allogenic products and
      potentially decrease transfusion related morbidity in mortality in this population.
Patients under 12 months of age requiring cardiopulmonary bypass surgery will be approached
      for the study. Patients with a pre- existing coagulopathy, including unexplained bleeding or
      history of clotting, will be excluded. Prior to the study beginning, patients will be
      randomized to our standard transfusion algorithm with cryoprecipitate or fibrinogen
      concentrate. As is standard of care, laboratory tests will be sent at standard times points

        1. after the induction of anesthesia,

        2. after initiation of bypass,

        3. after separation from bypass and administration of protamine, and transfusion of either
           fibrinogen concentrate or cryoprecipitate

        4. on arrival to the ICU. These laboratory tests include hematocrit, arterial blood gas,
           chemistry, thromboelastogram (TEG) and fibrinogen. Additional laboratory tests will be
           sent as indicated by the clinical scenario to determine transfusion requirements. For
           patients enrolled in the study, we will standardize the anesthetic management,
           cardiopulmonary bypass protocol, and transfusion thresholds in the operating room and
           ICU. We will collect demographic data, intraop and post-op laboratory values, bypass
           times, intraop and post op transfusion data, chest tube output, adverse events, and
           length of ventilation, ICU stay and hospital stay.

      For patients randomized to the study arm (fibrinogen concentrate), the fibrinogen level
      measured on bypass will be used to calculate the appropriate dose of fibrinogen concentrate
      to achieve a level of 300mg/dL after separation from bypass. Fibrinogen concentrate will
      replace cryoprecipitate in our post-operative transfusion algorithm. If the patient has
      continued bleeding based on laboratory values and clinical situation, the patient will be
      given cryoprecipitate as a rescue measure. Patients not on the study protocol will receive
      our normal transfusion algorithm.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Care Provider)
measure: Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival.
time frame: From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours)
description: For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets.
measure: Chest Tube Output
time frame: From administration end of surgery to 24 hours post operatively
description: Volume of chest tube drainage evaluated over first 24 hours post operatively
measure: Hours of Mechanical Ventilation
time frame: From administration of the drug during surgery to extubation in the ICU (up to 30 days)
measure: Length of Stay in Intensive Care Unit (ICU)
time frame: From administration of the drug during surgery to discharge from the ICU (up to 3 months)
measure: Length of Stay in Hospital
time frame: From administration of the drug during surgery to discharge from the hospital (up to 6 months)
measure: Count of Participants Who Died Within 30 Days Following Procedure
time frame: From administration of the drug to 30 days following surgery
arm group label: Cryoprecipitate Arm
arm group type: Active Comparator
description: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group
arm group label: Fibrinogen Concentrate Arm
arm group type: Active Comparator
description: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group
intervention type: Biological
intervention name: Fibrinogen Concentrate
description: Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group
arm group label: Fibrinogen Concentrate Arm
intervention type: Biological
intervention name: Cryoprecipitate
description: Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group
arm group label: Cryoprecipitate Arm
criteria: 
gender: All
minimum age: 1 Day
maximum age: 12 Months
healthy volunteers: No
last name: Glyn D Williams, MBChB, FFA
role: Principal Investigator
affiliation: Stanford University
last name: Laura Downey, MD
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Glyn David Williams
investigator title: Professor, Department of Anesthesiology, Perioperative and Pain Medicine
mesh term: Heart Diseases
mesh term: Heart Defects, Congenital
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 