<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/NCT02968654</url>
  </required_header>
  <id_info>
    <org_study_id>P2015/327</org_study_id>
    <nct_id>NCT02968654</nct_id>
    <nct_alias>NCT02962349</nct_alias>
  </id_info>
  <brief_title>TRansfusion Strategies in Acute Brain INjured Patients</brief_title>
  <acronym>TRAIN</acronym>
  <official_title>Transfusion Strategies in Acute Brain Injured Patients. A Prospective Multicenter Randomized Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Erasme University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Society of Intensive Care Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Erasme University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare a &quot;liberal&quot; and a &quot;restrictive&quot; strategy to administer blood transfusions in&#xD;
      critically ill patients with a primary brain injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Although blood transfusions can be lifesaving in severe hemorrhage, they can also have&#xD;
      potential complications. As anemia has also been associated with poor outcomes in critically&#xD;
      ill patients, determining an optimal transfusion trigger is a real challenge for clinicians.&#xD;
      This is even more important in patients with acute brain injury who were not specifically&#xD;
      evaluated in previous large randomized clinical trials dealing with the optimal transfusion&#xD;
      threshold. Neurological patients may be particularly sensitive to anemic brain hypoxia&#xD;
      because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue&#xD;
      oxygen demand.&#xD;
&#xD;
      This prospective, multicenter, randomized, pragmatic trial will compare two different&#xD;
      strategies for red blood cell transfusion in patients with acute brain injury: a &quot;liberal&quot;&#xD;
      strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL&#xD;
      and a &quot;restrictive&quot; approach in which the aim is to maintain Hb concentrations greater than 7&#xD;
      g/dL. The target population is patients suffering from traumatic brain injury (TBI),&#xD;
      subarachnoid hemorrhage (SAH) or intracranial hemorrhage (ICH).&#xD;
&#xD;
      The primary outcome is neurological outcome, evaluated using the extended Glasgow Outcome&#xD;
      Scale (eGOS), at 180 days after the initial injury. Secondary outcomes include, amongst&#xD;
      others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the&#xD;
      occurrence of extra-cerebral organ dysfunction/failure and the development of any infection&#xD;
      or thromboembolic events (venous or arterial).&#xD;
&#xD;
      The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome&#xD;
      (i.e. unfavorable neurological outcome) from 50% to 30% between groups (397 patients in each&#xD;
      arm). The study will be initiated in September 2016 in several European ICUs and is expected&#xD;
      at least 6 years.&#xD;
&#xD;
      The results of this trial will help to improve blood product and transfusion use in this&#xD;
      specific patient population and will provide additional data in some sub-groups of patients&#xD;
      at high-risk of brain ischemia, such as those with intracranial hypertension or cerebral&#xD;
      vasospasm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2016</start_date>
  <completion_date type="Actual">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Unfavorable Neurological Outcome</measure>
    <time_frame>180 days after randomization</time_frame>
    <description>Unfavorable neurological outcome is defined by the extended Glasgow Outcome Scale (eGOS) of 1-5</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>28 days</time_frame>
    <description>28 days Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the Glasgow Coma Score (GCS) over time</measure>
    <time_frame>28 days</time_frame>
    <description>modification of GCS from admission over the first week and vs. the last available</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>180 days</time_frame>
    <description>length of ICU stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>180 days</time_frame>
    <description>length oh hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence and severity of extra-cerebral organ dysfunction/failure</measure>
    <time_frame>28 days</time_frame>
    <description>Daily sequential organ failure assessment (SOFA) score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infection rate</measure>
    <time_frame>28 days</time_frame>
    <description>Occurrence of any infection over the first 28 days after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite outcome</measure>
    <time_frame>28 days</time_frame>
    <description>Death and Organ Failure (defined as at least one extra-cerebral organ failure, according to the specific SOFA sub-score &gt; 2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Oxygen Pressure</measure>
    <time_frame>28 days</time_frame>
    <description>Absolute values of brain oxygen pressure (PbO2) for those patients where this neuromonitoring has been implemented, according to the decision of the attending physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily Fluid Balance</measure>
    <time_frame>28 days</time_frame>
    <description>Assessment of the daily fluid balance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Events (SAE)</measure>
    <time_frame>28 days</time_frame>
    <description>Any of the &quot;SAE&quot; as described in the study protocol</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">850</enrollment>
  <condition>Acute Brain Injury</condition>
  <condition>Blood Transfusion</condition>
  <arm_group>
    <arm_group_label>Restrictive Transfusion Strategy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>&quot;Blood Transfusion&quot; will be given when hemoglobin concentration will be below 7 g/dL (as suggested by current guidelines in &quot;general&quot; ICU population)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Liberal Transfusion Strategy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>&quot;Blood Transfusion&quot; will be given when hemoglobin concentration will be below 9 g/dL</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Restrictive Transfusion Strategy</intervention_name>
    <description>Patients will be randomized when hemoglobin levels will be below 9 g/dl. Patients randomized to the &quot;Restrictive Transfusion Strategy&quot; will receive blood transfusion whenever their Hb concentration is &lt; 7 g/dl. All patients should preferably receive one unit of blood transfusion at a time. The duration of the intervention is 28 days after randomization or until hospital discharge. Daily assessment of hemoglobin levels are mandatory only during the ICU stay. No other procedures and or interventions are scheduled. General management of patients will be conducted according to international guidelines; however, local protocols and procedures are allowed.</description>
    <arm_group_label>Restrictive Transfusion Strategy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liberal Transfusion Strategy</intervention_name>
    <description>Patients will be randomized when hemoglobin levels will be below 9 g/dl. Patients randomized to the &quot;Liberal Transfusion Strategy&quot; will receive blood transfusion whenever their Hb concentration is &lt; 7 g/dl. All patients should preferably receive one unit of blood transfusion at a time. The duration of the intervention is 28 days after randomization or until hospital discharge. Daily assessment of hemoglobin levels are mandatory only during the ICU stay. No other procedures and or interventions are scheduled. General management of patients will be conducted according to international guidelines; however, local protocols and procedures are allowed.</description>
    <arm_group_label>Liberal Transfusion Strategy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Glasgow Coma Score (GCS) ≤ 13 on randomization&#xD;
&#xD;
          -  Expected ICU stay &gt; 72 hours&#xD;
&#xD;
          -  hemoglobin (Hb) concentration ≤ 9 g/dL within 10 days from brain injury&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Post-anoxic coma; status epilepticus without underlying brain injury; central nervous&#xD;
             system (CNS) infections (community-acquired; hospital-acquired; ventriculitis;&#xD;
             post-operative)&#xD;
&#xD;
          2. Known previous neurological disease, causing significant cognitive and/or motor&#xD;
             handicap&#xD;
&#xD;
          3. ICH due to arterio-venous malformation (AVM) or brain tumor&#xD;
&#xD;
          4. Inability (religious reasons) or reduced ability (lack of compatible blood) to receive&#xD;
             blood products&#xD;
&#xD;
          5. Active and uncontrolled bleeding at the time of enrollment&#xD;
&#xD;
          6. GCS of 3 with both pupils fixed and dilated; brain death or imminent death (within 24&#xD;
             hours)&#xD;
&#xD;
          7. Pregnancy&#xD;
&#xD;
          8. Medical need to correct anemia (e.g., active coronary disease or severe cardiac&#xD;
             disease) with target Hb levels &gt; 9 g/dL&#xD;
&#xD;
          9. do-not-escalate (DNE) orders&#xD;
&#xD;
         10. Previous allo-immunization due to transfusion, limiting red blood cells (RBC)&#xD;
             availability&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hopital Erasme</name>
      <address>
        <city>Brussels</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Erasme University Hospital</investigator_affiliation>
    <investigator_full_name>Fabio Taccone</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Blood Transfusion</keyword>
  <keyword>Brain Injury</keyword>
  <keyword>Outcome</keyword>
  <keyword>Hemoglobin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
  </condition_browse>
  <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/NCT02968654
org study id: P2015/327
nct id: NCT02968654
nct alias: NCT02962349
lead sponsor: 
collaborator: 
has dmc: Yes
To compare a "liberal" and a "restrictive" strategy to administer blood transfusions in
      critically ill patients with a primary brain injury.
Although blood transfusions can be lifesaving in severe hemorrhage, they can also have
      potential complications. As anemia has also been associated with poor outcomes in critically
      ill patients, determining an optimal transfusion trigger is a real challenge for clinicians.
      This is even more important in patients with acute brain injury who were not specifically
      evaluated in previous large randomized clinical trials dealing with the optimal transfusion
      threshold. Neurological patients may be particularly sensitive to anemic brain hypoxia
      because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue
      oxygen demand.

      This prospective, multicenter, randomized, pragmatic trial will compare two different
      strategies for red blood cell transfusion in patients with acute brain injury: a "liberal"
      strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL
      and a "restrictive" approach in which the aim is to maintain Hb concentrations greater than 7
      g/dL. The target population is patients suffering from traumatic brain injury (TBI),
      subarachnoid hemorrhage (SAH) or intracranial hemorrhage (ICH).

      The primary outcome is neurological outcome, evaluated using the extended Glasgow Outcome
      Scale (eGOS), at 180 days after the initial injury. Secondary outcomes include, amongst
      others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the
      occurrence of extra-cerebral organ dysfunction/failure and the development of any infection
      or thromboembolic events (venous or arterial).

      The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome
      (i.e. unfavorable neurological outcome) from 50% to 30% between groups (397 patients in each
      arm). The study will be initiated in September 2016 in several European ICUs and is expected
      at least 6 years.

      The results of this trial will help to improve blood product and transfusion use in this
      specific patient population and will provide additional data in some sub-groups of patients
      at high-risk of brain ischemia, such as those with intracranial hypertension or cerebral
      vasospasm.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Unfavorable Neurological Outcome
time frame: 180 days after randomization
description: Unfavorable neurological outcome is defined by the extended Glasgow Outcome Scale (eGOS) of 1-5
measure: Survival
time frame: 28 days
description: 28 days Survival
measure: Changes in the Glasgow Coma Score (GCS) over time
time frame: 28 days
description: modification of GCS from admission over the first week and vs. the last available
measure: ICU length of stay
time frame: 180 days
description: length of ICU stay
measure: Hospital length of stay
time frame: 180 days
description: length oh hospital stay
measure: Presence and severity of extra-cerebral organ dysfunction/failure
time frame: 28 days
description: Daily sequential organ failure assessment (SOFA) score
measure: Infection rate
time frame: 28 days
description: Occurrence of any infection over the first 28 days after randomization
measure: Composite outcome
time frame: 28 days
description: Death and Organ Failure (defined as at least one extra-cerebral organ failure, according to the specific SOFA sub-score > 2)
measure: Brain Oxygen Pressure
time frame: 28 days
description: Absolute values of brain oxygen pressure (PbO2) for those patients where this neuromonitoring has been implemented, according to the decision of the attending physician
measure: Daily Fluid Balance
time frame: 28 days
description: Assessment of the daily fluid balance
measure: Serious Adverse Events (SAE)
time frame: 28 days
description: Any of the "SAE" as described in the study protocol
arm group label: Restrictive Transfusion Strategy
arm group type: Other
description: "Blood Transfusion" will be given when hemoglobin concentration will be below 7 g/dL (as suggested by current guidelines in "general" ICU population)
arm group label: Liberal Transfusion Strategy
arm group type: Other
description: "Blood Transfusion" will be given when hemoglobin concentration will be below 9 g/dL
intervention type: Procedure
intervention name: Restrictive Transfusion Strategy
description: Patients will be randomized when hemoglobin levels will be below 9 g/dl. Patients randomized to the "Restrictive Transfusion Strategy" will receive blood transfusion whenever their Hb concentration is < 7 g/dl. All patients should preferably receive one unit of blood transfusion at a time. The duration of the intervention is 28 days after randomization or until hospital discharge. Daily assessment of hemoglobin levels are mandatory only during the ICU stay. No other procedures and or interventions are scheduled. General management of patients will be conducted according to international guidelines; however, local protocols and procedures are allowed.
arm group label: Restrictive Transfusion Strategy
intervention type: Procedure
intervention name: Liberal Transfusion Strategy
description: Patients will be randomized when hemoglobin levels will be below 9 g/dl. Patients randomized to the "Liberal Transfusion Strategy" will receive blood transfusion whenever their Hb concentration is < 7 g/dl. All patients should preferably receive one unit of blood transfusion at a time. The duration of the intervention is 28 days after randomization or until hospital discharge. Daily assessment of hemoglobin levels are mandatory only during the ICU stay. No other procedures and or interventions are scheduled. General management of patients will be conducted according to international guidelines; however, local protocols and procedures are allowed.
arm group label: Liberal Transfusion Strategy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: Erasme University Hospital
investigator full name: Fabio Taccone
investigator title: Professor
mesh term: Brain Injuries
sharing ipd: No