<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/NCT01675453</url>
  </required_header>
  <id_info>
    <org_study_id>ESHHS</org_study_id>
    <nct_id>NCT01675453</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of Hypertonic Saline in Cardiac Surgery Patients.</brief_title>
  <acronym>ESHHS</acronym>
  <official_title>The Efficacy and Safety of 7.2% NaCl Plus 6% Hydroxyethyl 200/0.5 in Patients Scheduled for First-time Coronary Artery Bypass Grafting With Cardiopulmonary Bypass.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meshalkin Research Institute of Pathology of Circulation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Meshalkin Research Institute of Pathology of Circulation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The organ dysfunction following cardiopulmonary bypass (CPB) occurs frequently in cardiac&#xD;
      surgery patients. Systemic inflammatory response initiated by CPB through releasing of&#xD;
      several mediators lead to altered endothelial integrity and in consequence the leakage of&#xD;
      proteins and fluids from the intravascular to the interstitial compartment is occurred.&#xD;
      Increased capillary permeability and decreased colloid osmotic pressure were shown to play a&#xD;
      key role for fluid shift and increasing of extravascular water. Further tissue edema can&#xD;
      result in injury to many organs, including the heart, lungs, brain, kidneys and can lead to&#xD;
      adverse outcomes.&#xD;
&#xD;
      Hypertonic solution creates an osmotic gradient across the cellular membrane, causing a fluid&#xD;
      shift from the intracellular and the interstitial spaces of tissue into the intravascular&#xD;
      compartment.&#xD;
&#xD;
      The purpose of this study is to investigate the efficacy and safety of 7.2% NaCl plus 6%&#xD;
      hydroxyethyl starch 200/0.5 in patients scheduled for first-time coronary artery bypass&#xD;
      grafting with cardiopulmonary bypass.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2012</start_date>
  <completion_date type="Actual">September 2012</completion_date>
  <primary_completion_date type="Actual">September 2012</primary_completion_date>
  <phase>Phase 2</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>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Extravascular Lung Water Index</measure>
    <time_frame>baseline; 5 min after infusion; 5 min after CPB; 30 min after CPB; end of surgery; 2 h, 4 h, 6 h, 12 h after CPB; Postoperative day 1</time_frame>
    <description>Extravascular lung water index (ELWI; mL/kg) will be used to assess this outcome measure. ELWI was monitored by transcardiopulmonary thermodilution technique with the PiCCO plus system. Extravascular lung water represents the extravascular fluid of the lung tissue. It includes intra-cellular, interstitial and intra-alveolar water (not pleural effusion). It is indexed to &quot;Predicted Body Weight&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Oxygenation</measure>
    <time_frame>24 hours</time_frame>
    <description>Index of arterial oxygenation efficiency (PaO2/FiO2), alveolar-arterial oxygen tension difference (AaDO2) will be used to assess this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen Delivery</measure>
    <time_frame>24 hours</time_frame>
    <description>Oxygen delivery index (DO2I) will be used to assess this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Index</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluid Balance</measure>
    <time_frame>24 hours</time_frame>
    <description>Net fluid balance at the end of surgery equals the sum of all infusions minus the urine output. Net fluid balance at postoperative day 1 equals the sum of all infusions minus the urine output and blood loss.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammation Response</measure>
    <time_frame>24 hours</time_frame>
    <description>Serum levels of Interleukin 6 (IL-6) and Interleukin 10 (IL-10) will be used to assess this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial Integrity</measure>
    <time_frame>24 hours</time_frame>
    <description>Serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin will be used to assess this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Na</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Osmolarity</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Acute Kidney Injury</measure>
    <time_frame>48 hours</time_frame>
    <description>serum creatinine, serum cystatin C, urine neutrophil gelatinase-associated lipocalin (uNGAL) will be used to asses this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Hyperchloremic Metabolic Acidosis</measure>
    <time_frame>24 hours</time_frame>
    <description>blood pH, base excess (BE), plasma level of Cl will be used to assess this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke Volume Index</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Neurological Complications</measure>
    <time_frame>24 hours</time_frame>
    <description>Delirium, clinically diagnosed stroke, and encephalopathy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Loss</measure>
    <time_frame>24 hours</time_frame>
    <description>Bleeding from chest tubes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Mechanical Ventilation</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chloride Loading</measure>
    <time_frame>24 h</time_frame>
    <description>The amount of chloride ions (mmol per patient) which will be infused during the surgery and ICU stay</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Edema</condition>
  <arm_group>
    <arm_group_label>7.2% NaCl /hydroxyethyl starch 200/0.5</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>On-pump CABG. 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 solution (HyperHAES) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.9% NaCl</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>On-pump CABG. 0.9% NaCl (isotonic saline) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>7.2% NaCl plus 6% hydroxyethyl starch 200/0.5</intervention_name>
    <arm_group_label>7.2% NaCl /hydroxyethyl starch 200/0.5</arm_group_label>
    <other_name>HyperHAES</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.9% NaCl</intervention_name>
    <arm_group_label>0.9% NaCl</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients scheduled for first-time coronary artery bypass grafting with cardiopulmonary&#xD;
             bypass&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &gt;70 years&#xD;
&#xD;
          -  body mass index &lt;18 and &gt;35 kg/m2&#xD;
&#xD;
          -  left ventricular ejection fraction &lt;40%&#xD;
&#xD;
          -  myocardial infarction &lt;6 months before surgery&#xD;
&#xD;
          -  stroke or transient ischemic attack &lt;12 months before surgery&#xD;
&#xD;
          -  diabetes mellitus&#xD;
&#xD;
          -  glomerular filtration rate &lt;90 mL/min&#xD;
&#xD;
          -  emergency surgery&#xD;
&#xD;
          -  hematocrit &lt;30%.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vladimir V Lomivorotov, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Novosibirsk Research Institute of Pathology of Circulation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novosibirsk Research Institute of Pathology of Circulation</name>
      <address>
        <city>Novosibirsk</city>
        <state>Novosibirsk territory</state>
        <zip>630055</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 5, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <results_first_submitted>May 18, 2014</results_first_submitted>
  <results_first_submitted_qc>May 18, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 19, 2014</results_first_posted>
  <last_update_submitted>April 29, 2016</last_update_submitted>
  <last_update_submitted_qc>April 29, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 27, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Meshalkin Research Institute of Pathology of Circulation</investigator_affiliation>
    <investigator_full_name>Evgeny Fominskiy, MD, PhD</investigator_full_name>
    <investigator_title>Anesthesiologist</investigator_title>
  </responsible_party>
  <keyword>Organ dysfunction</keyword>
  <keyword>Hypertonic solution</keyword>
  <keyword>Extravascular water</keyword>
  <keyword>Cardiopulmonary Bypass</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group)</title>
          <description>On-pump CABG. 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 solution (HyperHAES) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
7.2% NaCl plus 6% hydroxyethyl starch 200/0.5</description>
        </group>
        <group group_id="P2">
          <title>0.9% NaCl (Control Group)</title>
          <description>On-pump CABG. 0.9% NaCl (isotonic saline) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
0.9% NaCl</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group)</title>
          <description>On-pump CABG. 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 solution (HyperHAES) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
7.2% NaCl plus 6% hydroxyethyl starch 200/0.5</description>
        </group>
        <group group_id="B2">
          <title>0.9% NaCl (Control Group)</title>
          <description>On-pump CABG. 0.9% NaCl (isotonic saline) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
0.9% NaCl</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="20"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59" lower_limit="54" upper_limit="63"/>
                    <measurement group_id="B2" value="57" lower_limit="51" upper_limit="63"/>
                    <measurement group_id="B3" value="58" lower_limit="51" upper_limit="63"/>
                  </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="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Russian Federation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Extravascular Lung Water Index</title>
        <description>Extravascular lung water index (ELWI; mL/kg) will be used to assess this outcome measure. ELWI was monitored by transcardiopulmonary thermodilution technique with the PiCCO plus system. Extravascular lung water represents the extravascular fluid of the lung tissue. It includes intra-cellular, interstitial and intra-alveolar water (not pleural effusion). It is indexed to &quot;Predicted Body Weight&quot;.</description>
        <time_frame>baseline; 5 min after infusion; 5 min after CPB; 30 min after CPB; end of surgery; 2 h, 4 h, 6 h, 12 h after CPB; Postoperative day 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group)</title>
            <description>On-pump CABG. 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 solution (HyperHAES) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
7.2% NaCl plus 6% hydroxyethyl starch 200/0.5</description>
          </group>
          <group group_id="O2">
            <title>0.9% NaCl (Control Group)</title>
            <description>On-pump CABG. 0.9% NaCl (isotonic saline) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
0.9% NaCl</description>
          </group>
        </group_list>
        <measure>
          <title>Extravascular Lung Water Index</title>
          <description>Extravascular lung water index (ELWI; mL/kg) will be used to assess this outcome measure. ELWI was monitored by transcardiopulmonary thermodilution technique with the PiCCO plus system. Extravascular lung water represents the extravascular fluid of the lung tissue. It includes intra-cellular, interstitial and intra-alveolar water (not pleural effusion). It is indexed to &quot;Predicted Body Weight&quot;.</description>
          <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="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="8" upper_limit="10"/>
                    <measurement group_id="O2" value="8" lower_limit="8" upper_limit="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5 min after infusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="8" upper_limit="10"/>
                    <measurement group_id="O2" value="8" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5 min after CPB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="8" upper_limit="9"/>
                    <measurement group_id="O2" value="10" lower_limit="9" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 min after CPB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="8" upper_limit="9"/>
                    <measurement group_id="O2" value="9" lower_limit="9" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>end of surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="8" upper_limit="9"/>
                    <measurement group_id="O2" value="9" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 h after CPB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="8" upper_limit="9"/>
                    <measurement group_id="O2" value="9" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 h after CPB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="6" upper_limit="8"/>
                    <measurement group_id="O2" value="9" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 h after CPB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="6" upper_limit="7"/>
                    <measurement group_id="O2" value="9" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 h after CPB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="6" upper_limit="8"/>
                    <measurement group_id="O2" value="9" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>POD 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="7" upper_limit="8"/>
                    <measurement group_id="O2" value="9" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pulmonary Oxygenation</title>
        <description>Index of arterial oxygenation efficiency (PaO2/FiO2), alveolar-arterial oxygen tension difference (AaDO2) will be used to assess this outcome measure.</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oxygen Delivery</title>
        <description>Oxygen delivery index (DO2I) will be used to assess this outcome measure.</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cardiac Index</title>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fluid Balance</title>
        <description>Net fluid balance at the end of surgery equals the sum of all infusions minus the urine output. Net fluid balance at postoperative day 1 equals the sum of all infusions minus the urine output and blood loss.</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Inflammation Response</title>
        <description>Serum levels of Interleukin 6 (IL-6) and Interleukin 10 (IL-10) will be used to assess this outcome measure.</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Endothelial Integrity</title>
        <description>Serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin will be used to assess this outcome measure.</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Na</title>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Osmolarity</title>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Acute Kidney Injury</title>
        <description>serum creatinine, serum cystatin C, urine neutrophil gelatinase-associated lipocalin (uNGAL) will be used to asses this outcome measure.</description>
        <time_frame>48 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Hyperchloremic Metabolic Acidosis</title>
        <description>blood pH, base excess (BE), plasma level of Cl will be used to assess this outcome measure.</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stroke Volume Index</title>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Neurological Complications</title>
        <description>Delirium, clinically diagnosed stroke, and encephalopathy.</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Blood Loss</title>
        <description>Bleeding from chest tubes</description>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Mechanical Ventilation</title>
        <time_frame>24 hours</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Chloride Loading</title>
        <description>The amount of chloride ions (mmol per patient) which will be infused during the surgery and ICU stay</description>
        <time_frame>24 h</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group)</title>
          <description>On-pump CABG. 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 solution (HyperHAES) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
7.2% NaCl plus 6% hydroxyethyl starch 200/0.5</description>
        </group>
        <group group_id="E2">
          <title>0.9% NaCl (Control Group)</title>
          <description>On-pump CABG. 0.9% NaCl (isotonic saline) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)&#xD;
0.9% NaCl</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Evgeny Fominskiy</name_or_title>
      <organization>Academician EN Meshalkin State Budget Research Institute of Circulation Pathology</organization>
      <phone>+79139538754</phone>
      <email>evfominskiy@gmail.com</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/NCT01675453
org study id: ESHHS
nct id: NCT01675453
lead sponsor: 
has dmc: Yes
The organ dysfunction following cardiopulmonary bypass (CPB) occurs frequently in cardiac
      surgery patients. Systemic inflammatory response initiated by CPB through releasing of
      several mediators lead to altered endothelial integrity and in consequence the leakage of
      proteins and fluids from the intravascular to the interstitial compartment is occurred.
      Increased capillary permeability and decreased colloid osmotic pressure were shown to play a
      key role for fluid shift and increasing of extravascular water. Further tissue edema can
      result in injury to many organs, including the heart, lungs, brain, kidneys and can lead to
      adverse outcomes.

      Hypertonic solution creates an osmotic gradient across the cellular membrane, causing a fluid
      shift from the intracellular and the interstitial spaces of tissue into the intravascular
      compartment.

      The purpose of this study is to investigate the efficacy and safety of 7.2% NaCl plus 6%
      hydroxyethyl starch 200/0.5 in patients scheduled for first-time coronary artery bypass
      grafting with cardiopulmonary bypass.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Extravascular Lung Water Index
time frame: baseline; 5 min after infusion; 5 min after CPB; 30 min after CPB; end of surgery; 2 h, 4 h, 6 h, 12 h after CPB; Postoperative day 1
description: Extravascular lung water index (ELWI; mL/kg) will be used to assess this outcome measure. ELWI was monitored by transcardiopulmonary thermodilution technique with the PiCCO plus system. Extravascular lung water represents the extravascular fluid of the lung tissue. It includes intra-cellular, interstitial and intra-alveolar water (not pleural effusion). It is indexed to "Predicted Body Weight".
measure: Pulmonary Oxygenation
time frame: 24 hours
description: Index of arterial oxygenation efficiency (PaO2/FiO2), alveolar-arterial oxygen tension difference (AaDO2) will be used to assess this outcome measure.
measure: Oxygen Delivery
time frame: 24 hours
description: Oxygen delivery index (DO2I) will be used to assess this outcome measure.
measure: Cardiac Index
time frame: 24 hours
measure: Fluid Balance
time frame: 24 hours
description: Net fluid balance at the end of surgery equals the sum of all infusions minus the urine output. Net fluid balance at postoperative day 1 equals the sum of all infusions minus the urine output and blood loss.
measure: Inflammation Response
time frame: 24 hours
description: Serum levels of Interleukin 6 (IL-6) and Interleukin 10 (IL-10) will be used to assess this outcome measure.
measure: Endothelial Integrity
time frame: 24 hours
description: Serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin will be used to assess this outcome measure.
measure: Plasma Na
time frame: 24 hours
measure: Plasma Osmolarity
time frame: 24 hours
measure: Rate of Acute Kidney Injury
time frame: 48 hours
description: serum creatinine, serum cystatin C, urine neutrophil gelatinase-associated lipocalin (uNGAL) will be used to asses this outcome measure.
measure: Rate of Hyperchloremic Metabolic Acidosis
time frame: 24 hours
description: blood pH, base excess (BE), plasma level of Cl will be used to assess this outcome measure.
measure: Stroke Volume Index
time frame: 24 hours
measure: Rate of Neurological Complications
time frame: 24 hours
description: Delirium, clinically diagnosed stroke, and encephalopathy.
measure: Blood Loss
time frame: 24 hours
description: Bleeding from chest tubes
measure: Duration of Mechanical Ventilation
time frame: 24 hours
measure: Chloride Loading
time frame: 24 h
description: The amount of chloride ions (mmol per patient) which will be infused during the surgery and ICU stay
arm group label: 7.2% NaCl /hydroxyethyl starch 200/0.5
arm group type: Active Comparator
description: On-pump CABG. 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 solution (HyperHAES) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)
arm group label: 0.9% NaCl
arm group type: Placebo Comparator
description: On-pump CABG. 0.9% NaCl (isotonic saline) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB)
intervention type: Drug
intervention name: 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5
arm group label: 7.2% NaCl /hydroxyethyl starch 200/0.5
other name: HyperHAES
intervention type: Drug
intervention name: 0.9% NaCl
arm group label: 0.9% NaCl
other name: Saline
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: No
last name: Vladimir V Lomivorotov, MD, PhD
role: Principal Investigator
affiliation: Novosibirsk Research Institute of Pathology of Circulation
facility: 
country: Russian Federation
responsible party type: Principal Investigator
investigator affiliation: Meshalkin Research Institute of Pathology of Circulation
investigator full name: Evgeny Fominskiy, MD, PhD
investigator title: Anesthesiologist
mesh term: Coronary Artery Disease
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 