<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/NCT03837171</url>
  </required_header>
  <id_info>
    <org_study_id>K170913J</org_study_id>
    <secondary_id>2018-A00592-53</secondary_id>
    <nct_id>NCT03837171</nct_id>
  </id_info>
  <brief_title>TRANSfusion in Patients With Onco-hematological Malignancies ResusciTated From Septic Shock</brief_title>
  <acronym>TRANSPORT</acronym>
  <official_title>Stratégie Transfusionnelle érythrocytaire Dans la réanimation du Choc Septique du Patient d'Onco-hématologie : Essai randomisé Multicentrique TRANSPORT [TRANSfusion in Patients With Onco-hematological Malignancies ResusciTated From Septic Shock]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Septic shock is a frequent complication associated with high mortality in patients with&#xD;
      malignancies. The best transfusion strategy (restrictive or liberal) for the resuscitation of&#xD;
      septic shock remains a controversial issue, in relation with potentially discrepant goals of&#xD;
      tissue oxygenation and transfusion sparing.&#xD;
&#xD;
      In this study, the investigators propose to address the efficacy of two RBC transfusion&#xD;
      strategies (liberal or restrictive) in restoring appropriate tissue oxygenation as well as&#xD;
      their tolerance.&#xD;
&#xD;
      The investigators designed a prospective randomized multicenter trial aimed at comparing&#xD;
      liberal and restrictive RBC transfusion strategies applied during the first 48 hours of&#xD;
      resuscitation in cancer patients with septic shock and anemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Septic shock is a frequent complication in patients with malignancies and remains affected&#xD;
      with a mortality rate higher than 50%.&#xD;
&#xD;
      Red blood cell (RBC) transfusion remains a major issue for critically ill cancer patients who&#xD;
      frequently display anemia as a result of malignant bone marrow involvement or imposed by&#xD;
      cytotoxic treatments. However, our current practice of RBC transfusion in the intensive care&#xD;
      unit (ICU) is drawn from general populations. Several case-control studies suggested that RBC&#xD;
      transfusion was associated with higher mortality and increased incidence of ICU-acquired&#xD;
      complications in critically ill patients. In 1999, a restrictive strategy of&#xD;
      non-leucodepleted RBC transfusion to maintain hemoglobin above 7 g/dL was shown to be as&#xD;
      effective as a liberal transfusion strategy aimed to maintain haemoglobin &gt; 10 g/dL in&#xD;
      critically ill patients. As of today, the current recommendations for RBC transfusion remain&#xD;
      largely based on this study which excluded patients with a history of anemia. Leucodepletion&#xD;
      that is now routinely implemented in France might be associated with fewer&#xD;
      transfusion-related events. Indeed, some recent studies challenged the restrictive strategy&#xD;
      and suggested that a higher transfusion threshold might be beneficial in septic patients for&#xD;
      whom oxygen delivery is of paramount importance. Most importantly, a hemodynamic support&#xD;
      algorithm for severe sepsis also known as early goal-directed therapy (EGDT) included a&#xD;
      hematocrit target of 30%. The majority of EGDT-treated patients received RBC transfusion&#xD;
      within the early 72 hours of resuscitation, thereby representing a major difference compared&#xD;
      to standard treatment, but the prognostic value of RBC transfusion was not specifically&#xD;
      assessed. A recent case-control study also suggested that RBC transfusion was an independent&#xD;
      predictor of survival in patients with septic shock.&#xD;
&#xD;
      Cancer patients with septic shock and hemoglobin level &lt; 9 g/dL initiation will be randomized&#xD;
      to the interventional arm (liberal transfusion strategy to maintain hemoglobin &gt; 9 g/dL) or&#xD;
      to the control arm (restrictive transfusion strategy to maintain hemoglobin &gt; 7 g/dL) in a&#xD;
      1:1 ratio.&#xD;
&#xD;
      Patients from the intervention arm will have their hemoglobin level maintained above 9 g/dL&#xD;
      for the whole time under vasopressors, for a maximum of 28 days. After weaning from&#xD;
      vasopressor, the transfusion threshold will be lowered to 7 g/dL as recommended by the SSC&#xD;
      guidelines. In case of shock relapse requiring reintroduction of vasopressors, the&#xD;
      transfusion threshold will be upgraded back to 9 g/dL until next catecholamine weaning.&#xD;
&#xD;
      In the control arm, the transfusion threshold will be 7 g/dL until ICU discharge regardless&#xD;
      of catecholamine administration.&#xD;
&#xD;
      The primary objective of the study will be the restoration of tissue oxygenation as assessed&#xD;
      by lactate clearance at 12 hours following randomization. The secondary endpoints will be&#xD;
      related to restoration of tissue oxygenation at alternative time points (6h, 24h, 36h, 48h)&#xD;
      as assessed as above, the 7-day, 28-day, in-ICU and in-hospital mortality rate, changes in&#xD;
      organ failures over the first 48 hours and 7 days, duration for organ failure supports, the&#xD;
      development of acute ischemic and thrombotic events (myocardial infarction, mesenteric&#xD;
      ischemia, ischemic stroke, limb ischemia, deep venous thrombosis) over the first 7 days.&#xD;
&#xD;
      An interim analysis on the primary endpoint has been pre-planned at the end of the follow up&#xD;
      of half of patients included.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 24, 2019</start_date>
  <completion_date type="Anticipated">February 20, 2022</completion_date>
  <primary_completion_date type="Anticipated">February 20, 2021</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tissue oxygenation</measure>
    <time_frame>12 hours</time_frame>
    <description>Percentage of patients with normal arterial lactate level at 12 hours (&lt;=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH12)/lactate H0*100.&#xD;
lactateH0 : arterial lactate level at inclusion lactateH12 : arterial lactate level at 12h</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tissue oxygenation 6</measure>
    <time_frame>6 hours</time_frame>
    <description>Percentage of patients with normal arterial lactate level at 6 hours (&lt;=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH6)/lactate H0*100.&#xD;
lactateH0 : arterial lactate level at inclusion lactateH6 : arterial lactate level at 6h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tissue oxygenation 24</measure>
    <time_frame>24 hours</time_frame>
    <description>Percentage of patients with normal arterial lactate level at 24 hours (&lt;=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH24)/lactate H0*100.&#xD;
lactateH0 : arterial lactate level at inclusion lactateH24 : arterial lactate level at 24h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tissue oxygenation 48</measure>
    <time_frame>48 hours</time_frame>
    <description>Percentage of patients with normal arterial lactate level at 48 hours (&lt;=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH48)/lactate H0*100.&#xD;
lactateH0 : arterial lactate level at inclusion lactateH48 : arterial lactate level at 48h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality 7</measure>
    <time_frame>7 days</time_frame>
    <description>Percentage of Death at 7 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality 28</measure>
    <time_frame>28 days</time_frame>
    <description>Percentage of Death at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU mortality</measure>
    <time_frame>28 days</time_frame>
    <description>Percentage of Death in ICU at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital mortality</measure>
    <time_frame>28 days</time_frame>
    <description>Percentage of Death in Hospital at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SOFA 24</measure>
    <time_frame>24 hours</time_frame>
    <description>Differences between SOFA score at inclusion (SOFA0) and SOFA score at 24 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).&#xD;
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on &quot;sepsis-related problems&quot; of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SOFA 48</measure>
    <time_frame>48 hours</time_frame>
    <description>Differences between SOFA score at inclusion (SOFA0) and SOFA score at 48 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).&#xD;
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on &quot;sepsis-related problems&quot; of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SOFA 72</measure>
    <time_frame>72 hours</time_frame>
    <description>Differences between SOFA score at inclusion (SOFA0) and SOFA score at 72 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).&#xD;
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on &quot;sepsis-related problems&quot; of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SOFA 7d</measure>
    <time_frame>7 days</time_frame>
    <description>Differences between SOFA score at inclusion (SOFA0) and SOFA score at day 7. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).&#xD;
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on &quot;sepsis-related problems&quot; of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ventilator free days</measure>
    <time_frame>28 days</time_frame>
    <description>ventilator free days (VFDs) are defined as follows: VFDs=0: If the patient dies before 28 days. VFDs=(28-x): If the patient is success-fully weaned from mechanical ventilation within 28 days, where x is the number of days spent receiving mechanical ventilation.&#xD;
VFDs=0: If the patient requires mechanical ventilation for 28 days or more.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>vasopressor free days</measure>
    <time_frame>28 days</time_frame>
    <description>vasopressor free days (VaFDs) are defined as follows: VaFDs=0: If the patient dies before 28 days. VaFDs=(28-x): If the patient is successfully weaned from vasopressor within 28 days, where x is the number of days spent with vasopressor.&#xD;
VaFDs=0: If the patient requires vasopressor for 28 days or more.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>renal replacement therapy free days</measure>
    <time_frame>28 days</time_frame>
    <description>renal replacement therapy free days (RRFDs) are defined as follows: RRFDs=0: If the patient dies before 28 days. RRFDs=(28-x): If the patient is successfully weaned from renal replacement therapy within 28 days, where x is the number of days spent with vasopressor.&#xD;
RRFDs=0: If the patient requires renal replacement therapy for 28 days or more.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>28 days</time_frame>
    <description>time spent in ICU from inclusion censored at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ischemic</measure>
    <time_frame>28 days</time_frame>
    <description>Incidence of ischemic event during the first 28 days (stroke, myocardial infarction, mesenteric infarction)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>thrombosis</measure>
    <time_frame>28 days</time_frame>
    <description>Incidence of deep venous thrombosis or pulmonary embolism during the first 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRIALI</measure>
    <time_frame>28 days</time_frame>
    <description>Incidence of transfusion-related acute lung injury during the first 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transfusion reaction</measure>
    <time_frame>28 days</time_frame>
    <description>Incidence of side effects of transfusions during the first 28 days (fever, chills, hemolysis)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">260</enrollment>
  <condition>Septic Shock</condition>
  <condition>Anemia</condition>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Liberal strategy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Maintain a hemoglobin level &gt; 9 g/dL during the first 48 hours of resuscitation of septic shock</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Restrictive strategy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Maintain a hemoglobin level &gt; 7 g/dL during the resuscitation of septic shock</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Liberal Red blood cell transfusion</intervention_name>
    <description>Hemoglobin level will be maintained above 9 g/dL (liberal strategy) for the first 48 hours following randomization. After 48 hours, indications of RBC transfusions will be at the discretion of attending physicians in patients with persistent circulatory failure.&#xD;
After resolution of acute circulatory failure, a 7 g/dL transfusion threshold will be recommended regardless of the allocation arm. In case of subsequent episodes of septic shock, the transfusion strategy will be at the discretion of attending physicians</description>
    <arm_group_label>Liberal strategy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Restrictive Red blood cell transfusion</intervention_name>
    <description>Hemoglobin level will be maintained above 7 g/dL (restrictive strategy) during all the stay in ICU</description>
    <arm_group_label>Restrictive strategy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Evolutive (complete remission &lt; 2 years) malignant solid tumor or chronic or acute&#xD;
             hematological malignancy&#xD;
&#xD;
          -  Septic shock defined as:&#xD;
&#xD;
          -  Presumed or documented infection&#xD;
&#xD;
          -  Acute circulatory failure defined as hypotension requirement of vasoactive drugs for&#xD;
             more than one hour (norepinephrine or epinephrine ≥ 0.1 µg/kg/min)&#xD;
&#xD;
          -  Tissue hypoxia defined by arterial lactate level &gt; 2 mmol/L within 12 hours prior to&#xD;
             inclusion&#xD;
&#xD;
          -  Hemoglobin level &lt; 9 g/dL&#xD;
&#xD;
          -  Informed consent from patients or surrogates&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute life-threatening bleeding&#xD;
&#xD;
          -  Ongoing acute coronary syndrome or any other acute ischemic condition&#xD;
&#xD;
          -  End-of-life decisions at the time of ICU admission&#xD;
&#xD;
          -  Refusal of transfusions for personal beliefs&#xD;
&#xD;
          -  Lack of social security coverage&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Frederic PENE, MD, PhD</last_name>
    <phone>158414677</phone>
    <phone_ext>+33</phone_ext>
    <email>frederic.pene@cch.aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Matthieu RESCHE-RIGON, MD PhD</last_name>
    <phone>142499742</phone>
    <phone_ext>+33</phone_ext>
    <email>matthieu.resche-rigon@univ-paris-diderot.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>hopital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>frederic PENE, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>March 27, 2019</last_update_submitted>
  <last_update_submitted_qc>March 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Septic Shock</keyword>
  <keyword>Anemia</keyword>
  <keyword>cancer</keyword>
  <keyword>erythrocyte transfusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03837171
org study id: K170913J
secondary id: 2018-A00592-53
nct id: NCT03837171
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Septic shock is a frequent complication associated with high mortality in patients with
      malignancies. The best transfusion strategy (restrictive or liberal) for the resuscitation of
      septic shock remains a controversial issue, in relation with potentially discrepant goals of
      tissue oxygenation and transfusion sparing.

      In this study, the investigators propose to address the efficacy of two RBC transfusion
      strategies (liberal or restrictive) in restoring appropriate tissue oxygenation as well as
      their tolerance.

      The investigators designed a prospective randomized multicenter trial aimed at comparing
      liberal and restrictive RBC transfusion strategies applied during the first 48 hours of
      resuscitation in cancer patients with septic shock and anemia.
Septic shock is a frequent complication in patients with malignancies and remains affected
      with a mortality rate higher than 50%.

      Red blood cell (RBC) transfusion remains a major issue for critically ill cancer patients who
      frequently display anemia as a result of malignant bone marrow involvement or imposed by
      cytotoxic treatments. However, our current practice of RBC transfusion in the intensive care
      unit (ICU) is drawn from general populations. Several case-control studies suggested that RBC
      transfusion was associated with higher mortality and increased incidence of ICU-acquired
      complications in critically ill patients. In 1999, a restrictive strategy of
      non-leucodepleted RBC transfusion to maintain hemoglobin above 7 g/dL was shown to be as
      effective as a liberal transfusion strategy aimed to maintain haemoglobin > 10 g/dL in
      critically ill patients. As of today, the current recommendations for RBC transfusion remain
      largely based on this study which excluded patients with a history of anemia. Leucodepletion
      that is now routinely implemented in France might be associated with fewer
      transfusion-related events. Indeed, some recent studies challenged the restrictive strategy
      and suggested that a higher transfusion threshold might be beneficial in septic patients for
      whom oxygen delivery is of paramount importance. Most importantly, a hemodynamic support
      algorithm for severe sepsis also known as early goal-directed therapy (EGDT) included a
      hematocrit target of 30%. The majority of EGDT-treated patients received RBC transfusion
      within the early 72 hours of resuscitation, thereby representing a major difference compared
      to standard treatment, but the prognostic value of RBC transfusion was not specifically
      assessed. A recent case-control study also suggested that RBC transfusion was an independent
      predictor of survival in patients with septic shock.

      Cancer patients with septic shock and hemoglobin level < 9 g/dL initiation will be randomized
      to the interventional arm (liberal transfusion strategy to maintain hemoglobin > 9 g/dL) or
      to the control arm (restrictive transfusion strategy to maintain hemoglobin > 7 g/dL) in a
      1:1 ratio.

      Patients from the intervention arm will have their hemoglobin level maintained above 9 g/dL
      for the whole time under vasopressors, for a maximum of 28 days. After weaning from
      vasopressor, the transfusion threshold will be lowered to 7 g/dL as recommended by the SSC
      guidelines. In case of shock relapse requiring reintroduction of vasopressors, the
      transfusion threshold will be upgraded back to 9 g/dL until next catecholamine weaning.

      In the control arm, the transfusion threshold will be 7 g/dL until ICU discharge regardless
      of catecholamine administration.

      The primary objective of the study will be the restoration of tissue oxygenation as assessed
      by lactate clearance at 12 hours following randomization. The secondary endpoints will be
      related to restoration of tissue oxygenation at alternative time points (6h, 24h, 36h, 48h)
      as assessed as above, the 7-day, 28-day, in-ICU and in-hospital mortality rate, changes in
      organ failures over the first 48 hours and 7 days, duration for organ failure supports, the
      development of acute ischemic and thrombotic events (myocardial infarction, mesenteric
      ischemia, ischemic stroke, limb ischemia, deep venous thrombosis) over the first 7 days.

      An interim analysis on the primary endpoint has been pre-planned at the end of the follow up
      of half of patients included.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Tissue oxygenation
time frame: 12 hours
description: Percentage of patients with normal arterial lactate level at 12 hours (<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH12)/lactate H0*100.
lactateH0 : arterial lactate level at inclusion lactateH12 : arterial lactate level at 12h
measure: Tissue oxygenation 6
time frame: 6 hours
description: Percentage of patients with normal arterial lactate level at 6 hours (<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH6)/lactate H0*100.
lactateH0 : arterial lactate level at inclusion lactateH6 : arterial lactate level at 6h
measure: Tissue oxygenation 24
time frame: 24 hours
description: Percentage of patients with normal arterial lactate level at 24 hours (<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH24)/lactate H0*100.
lactateH0 : arterial lactate level at inclusion lactateH24 : arterial lactate level at 24h
measure: Tissue oxygenation 48
time frame: 48 hours
description: Percentage of patients with normal arterial lactate level at 48 hours (<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH48)/lactate H0*100.
lactateH0 : arterial lactate level at inclusion lactateH48 : arterial lactate level at 48h
measure: Mortality 7
time frame: 7 days
description: Percentage of Death at 7 days
measure: Mortality 28
time frame: 28 days
description: Percentage of Death at 28 days
measure: ICU mortality
time frame: 28 days
description: Percentage of Death in ICU at 28 days
measure: Hospital mortality
time frame: 28 days
description: Percentage of Death in Hospital at 28 days
measure: Change in SOFA 24
time frame: 24 hours
description: Differences between SOFA score at inclusion (SOFA0) and SOFA score at 24 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
measure: Change in SOFA 48
time frame: 48 hours
description: Differences between SOFA score at inclusion (SOFA0) and SOFA score at 48 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
measure: Change in SOFA 72
time frame: 72 hours
description: Differences between SOFA score at inclusion (SOFA0) and SOFA score at 72 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
measure: Change in SOFA 7d
time frame: 7 days
description: Differences between SOFA score at inclusion (SOFA0) and SOFA score at day 7. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient).
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
measure: ventilator free days
time frame: 28 days
description: ventilator free days (VFDs) are defined as follows: VFDs=0: If the patient dies before 28 days. VFDs=(28-x): If the patient is success-fully weaned from mechanical ventilation within 28 days, where x is the number of days spent receiving mechanical ventilation.
VFDs=0: If the patient requires mechanical ventilation for 28 days or more.
measure: vasopressor free days
time frame: 28 days
description: vasopressor free days (VaFDs) are defined as follows: VaFDs=0: If the patient dies before 28 days. VaFDs=(28-x): If the patient is successfully weaned from vasopressor within 28 days, where x is the number of days spent with vasopressor.
VaFDs=0: If the patient requires vasopressor for 28 days or more.
measure: renal replacement therapy free days
time frame: 28 days
description: renal replacement therapy free days (RRFDs) are defined as follows: RRFDs=0: If the patient dies before 28 days. RRFDs=(28-x): If the patient is successfully weaned from renal replacement therapy within 28 days, where x is the number of days spent with vasopressor.
RRFDs=0: If the patient requires renal replacement therapy for 28 days or more.
measure: ICU length of stay
time frame: 28 days
description: time spent in ICU from inclusion censored at 28 days
measure: Ischemic
time frame: 28 days
description: Incidence of ischemic event during the first 28 days (stroke, myocardial infarction, mesenteric infarction)
measure: thrombosis
time frame: 28 days
description: Incidence of deep venous thrombosis or pulmonary embolism during the first 28 days
measure: TRIALI
time frame: 28 days
description: Incidence of transfusion-related acute lung injury during the first 28 days
measure: Transfusion reaction
time frame: 28 days
description: Incidence of side effects of transfusions during the first 28 days (fever, chills, hemolysis)
arm group label: Liberal strategy
arm group type: Active Comparator
description: Maintain a hemoglobin level > 9 g/dL during the first 48 hours of resuscitation of septic shock
arm group label: Restrictive strategy
arm group type: Experimental
description: Maintain a hemoglobin level > 7 g/dL during the resuscitation of septic shock
intervention type: Biological
intervention name: Liberal Red blood cell transfusion
description: Hemoglobin level will be maintained above 9 g/dL (liberal strategy) for the first 48 hours following randomization. After 48 hours, indications of RBC transfusions will be at the discretion of attending physicians in patients with persistent circulatory failure.
After resolution of acute circulatory failure, a 7 g/dL transfusion threshold will be recommended regardless of the allocation arm. In case of subsequent episodes of septic shock, the transfusion strategy will be at the discretion of attending physicians
arm group label: Liberal strategy
intervention type: Biological
intervention name: Restrictive Red blood cell transfusion
description: Hemoglobin level will be maintained above 7 g/dL (restrictive strategy) during all the stay in ICU
arm group label: Restrictive strategy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Frederic PENE, MD, PhD
phone: 158414677
phone ext: +33
email: frederic.pene@cch.aphp.fr
last name: Matthieu RESCHE-RIGON, MD PhD
phone: 142499742
phone ext: +33
email: matthieu.resche-rigon@univ-paris-diderot.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Shock, Septic
mesh term: Hematologic Neoplasms
mesh term: Shock
sharing ipd: Undecided