<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/NCT03037424</url>
  </required_header>
  <id_info>
    <org_study_id>16-5636-A</org_study_id>
    <nct_id>NCT03037424</nct_id>
  </id_info>
  <brief_title>FIBrinogen REplenishment in Surgery</brief_title>
  <acronym>FIBRES</acronym>
  <official_title>Prospective, Multi-center, Randomized, Active-control, Non-inferiority Study Comparing Fibrinogen Concentrate With Cryoprecipitate for the Treatment of Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</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>
      This is a pragmatic, prospective, multi-center, randomized, active-control, single-blinded,&#xD;
      non-inferiority phase 3 trial in adult cardiac surgical patients. Up to 12 Canadian hospitals&#xD;
      will participate, and the trial will require up to 2 years for patient recruitment.&#xD;
&#xD;
      Twelve-hundred bleeding adult cardiac surgical patients who require fibrinogen&#xD;
      supplementation due to acquired hypofibrinogenemia after CPB will be included. Patients will&#xD;
      be randomized to receive equivalent doses of either fibrinogen concentrate (Octafibrin) or&#xD;
      cryoprecipitate when the blood bank receives the first order for fibrinogen supplementation&#xD;
      and deems it to be in accordance with accepted clinical standards. Thereafter, patients will&#xD;
      be treated according to their assigned group each time fibrinogen supplementation is ordered&#xD;
      during the treatment period (24 hours after termination of CPB). No other aspects of care&#xD;
      will be modified.&#xD;
&#xD;
      The primary efficacy outcome will be the number of Allogeneic blood products (ABP) (red blood&#xD;
      cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24&#xD;
      hours after termination of CPB. Safety outcomes will be measured for the first 28 days after&#xD;
      surgery, which is the duration of participation of each patient in the trial. Comparisons&#xD;
      will be by intention-to-treat (ITT) (primary) and per-protocol (PP) analysis. One interim&#xD;
      analysis will be conducted after 600 patients have been treated to determine whether the&#xD;
      study should be terminated for safety reasons, demonstrated non-inferiority or futility&#xD;
      reasons.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 22, 2017</start_date>
  <completion_date type="Actual">March 27, 2019</completion_date>
  <primary_completion_date type="Actual">November 30, 2018</primary_completion_date>
  <phase>Phase 3</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 (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary endpoint, which is of efficacy, is the comparison of the total number of units of ABPs (RBCs, pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB.</measure>
    <time_frame>24 hours</time_frame>
    <description>The number of ABPs (red blood cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">827</enrollment>
  <condition>Deficiency; Fibrinogen, Acquired</condition>
  <arm_group>
    <arm_group_label>Fibrinogen concentrate Octafibrin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cryoprecipitate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Octafibrin</intervention_name>
    <description>Octafibrin will be administered when the blood bank receives an order for fibrinogen supplementation</description>
    <arm_group_label>Fibrinogen concentrate Octafibrin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cryoprecipitate</intervention_name>
    <description>Cryoprecipitate will be administered when the blood bank receives an order for fibrinogen supplementation</description>
    <arm_group_label>Cryoprecipitate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. Patients undergoing index cardiac surgery with CPB in whom fibrinogen supplementation is&#xD;
        ordered in accordance with accepted clinical standards (significant hemorrhage and known or&#xD;
        presumed hypofibrinogenemia).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Receipt of fibrinogen rich products (fibrinogen concentrate or cryoprecipitate) within&#xD;
        24 hours before surgery 2. History of severe allergic reaction to cryoprecipitate or&#xD;
        fibrinogen concentrate 3. Refusal of ABPs, fibrinogen concentrate or cryoprecipitate due to&#xD;
        religious or other reasons 4. Fibrinogen level known to be &gt;3.0 g/L within 30 minutes of&#xD;
        IMP order (to eliminate the risk of raising patients' fibrinogen levels to &gt;4.0 g/L with&#xD;
        supplementation 5. Known pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Keyvan Karkouti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Health Network, Toronto</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fraser University Royal Columbia</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V3L 3W7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Manitoba, St Boniface General Hospital</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R2H 2A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Science Centre, McMaster University</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8S 3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kingston General Hsopital</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 3N6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Science Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Ottawa Heart Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y 4W7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Science Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5B 1W8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tornoto General Hospital, University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal Heart Institute</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H1T 1C8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval</name>
      <address>
        <city>Quebec</city>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>May 13, 2019</last_update_submitted>
  <last_update_submitted_qc>May 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Health Network, Toronto</investigator_affiliation>
    <investigator_full_name>Jo Carroll</investigator_full_name>
    <investigator_title>Manager Anesthesia Research</investigator_title>
  </responsible_party>
  <keyword>Cyroprecipitate</keyword>
  <keyword>Fibrinogen</keyword>
  <keyword>Cardiac Surgery</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03037424
org study id: 16-5636-A
nct id: NCT03037424
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a pragmatic, prospective, multi-center, randomized, active-control, single-blinded,
      non-inferiority phase 3 trial in adult cardiac surgical patients. Up to 12 Canadian hospitals
      will participate, and the trial will require up to 2 years for patient recruitment.

      Twelve-hundred bleeding adult cardiac surgical patients who require fibrinogen
      supplementation due to acquired hypofibrinogenemia after CPB will be included. Patients will
      be randomized to receive equivalent doses of either fibrinogen concentrate (Octafibrin) or
      cryoprecipitate when the blood bank receives the first order for fibrinogen supplementation
      and deems it to be in accordance with accepted clinical standards. Thereafter, patients will
      be treated according to their assigned group each time fibrinogen supplementation is ordered
      during the treatment period (24 hours after termination of CPB). No other aspects of care
      will be modified.

      The primary efficacy outcome will be the number of Allogeneic blood products (ABP) (red blood
      cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24
      hours after termination of CPB. Safety outcomes will be measured for the first 28 days after
      surgery, which is the duration of participation of each patient in the trial. Comparisons
      will be by intention-to-treat (ITT) (primary) and per-protocol (PP) analysis. One interim
      analysis will be conducted after 600 patients have been treated to determine whether the
      study should be terminated for safety reasons, demonstrated non-inferiority or futility
      reasons.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: The primary endpoint, which is of efficacy, is the comparison of the total number of units of ABPs (RBCs, pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB.
time frame: 24 hours
description: The number of ABPs (red blood cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB
arm group label: Fibrinogen concentrate Octafibrin
arm group type: Active Comparator
arm group label: Cryoprecipitate
arm group type: Active Comparator
intervention type: Drug
intervention name: Octafibrin
description: Octafibrin will be administered when the blood bank receives an order for fibrinogen supplementation
arm group label: Fibrinogen concentrate Octafibrin
intervention type: Drug
intervention name: Cryoprecipitate
description: Cryoprecipitate will be administered when the blood bank receives an order for fibrinogen supplementation
arm group label: Cryoprecipitate
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Keyvan Karkouti, MD
role: Principal Investigator
affiliation: University Health Network, Toronto
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University Health Network, Toronto
investigator full name: Jo Carroll
investigator title: Manager Anesthesia Research
sharing ipd: No