<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/NCT03772990</url>
  </required_header>
  <id_info>
    <org_study_id>21/2019</org_study_id>
    <nct_id>NCT03772990</nct_id>
  </id_info>
  <brief_title>Calcium Administration in Cardiac Surgery</brief_title>
  <acronym>ICARUS</acronym>
  <official_title>Calcium Administration in Patients Undergoing Cardiac Surgery Under Cardiopulmonary Bypass (ICARUS Trial): Prospective Randomized, Double-blind Placebo-controlled Superiority Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meshalkin Research Institute of Pathology of Circulation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Università Vita-Salute San Raffaele</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Meshalkin Research Institute of Pathology of Circulation</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>
      Termination of cardiopulmonary bypass is a critical step in any cardiac surgical procedure&#xD;
      and requires a thorough planning. Debate about rationale of calcium administration during&#xD;
      weaning of cardiopulmonary bypass has been conducted for several decades; however, a&#xD;
      consensus has not been yet reached.&#xD;
&#xD;
      Perioperative hypocalcemia can develop because of haemodilution or calcium binding from&#xD;
      heparin, albumin and citrate. Perioperative hypocalcemia is often complicated by development&#xD;
      of arrhythmias, especially QT interval prolongation. Furthermore, low content of calcium can&#xD;
      lead to vascular tone disorders, violation of neuromuscular transmission, altered hemostasis&#xD;
      and heart failure, resistant to inotropic agents, especially in patients with concomitant&#xD;
      cardiomyopathy.&#xD;
&#xD;
      On the other hand, hypercalcaemia is a dangerous complication in cardiac surgery. Among the&#xD;
      fatal, but rather rare complications, there are acute pancreatitis and the phenomenon of the&#xD;
      &quot;stone heart&quot;, which is essentially a reperfusion injury of the myocardium caused by rapid&#xD;
      calcium overload. Hypercalcaemia can also trigger rhythm disturbances, hypertension, increase&#xD;
      systemic vascular resistance, reduce diastolic compliance and impair relaxation of the&#xD;
      myocardium due to excessive calcium intake into the cardiomyocytes, cause coronary vasospasm&#xD;
      and aggravate ischaemic myocardial damage, impair arterial graft blood flow during&#xD;
      aortocoronary and mammary coronary bypass surgery.&#xD;
&#xD;
      To date, there is a lack of data indicating clinical efficacy of calcium administration&#xD;
      before separation from CPB. Therefore, we designed this randomized controlled trial to test&#xD;
      the hypothesis whether calcium administration at termination of CPB will reduce the need for&#xD;
      inotropic support at the end of surgery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Anticipated">March 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">February 27, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Inotropic support</measure>
    <time_frame>Intraoperatively</time_frame>
    <description>Number of patients requiring inotropic support before transfer to intensive care unit</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of inotropic support after surgery</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>Duration of infusion of any vasoinotropic agent at any dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vasoactive-inotropic score</measure>
    <time_frame>Postoperative day 1</time_frame>
    <description>Vasoactive-inotropic score will be measured on the morning of postoperative day 1. The inotropic score will be calculated using the following formula: Dobutamine dose (in mcg/kg/min) + Dopamine dose (in mcg/kg/min) + Enoximone dose (in mcg/kg/min) + [Epinephrine dose (in mcg/kg/min) x 100] + [Norepinephrine dose (in mcg/kg/min) x 100].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Ca2+ concentration before and after drug administration</measure>
    <time_frame>Intraoperatively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent in theatre after cardiopulmonary bypass</measure>
    <time_frame>Intraoperatively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ventilation</measure>
    <time_frame>Up to 30 day after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of intensive care unit stay</measure>
    <time_frame>Up to 30 day after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial infarction</measure>
    <time_frame>Up to 30 day after randomization</time_frame>
    <description>Number of patients who develop myocardial infarction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atrial fibrillation</measure>
    <time_frame>Up to 30 day after randomization</time_frame>
    <description>Number of patients who develop postoperative atrial fibrillation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type 1 and type 2 neurological complications</measure>
    <time_frame>Up to 30 day after randomization</time_frame>
    <description>Number of patients who develop type 1 and type 2 develop myocardial infarction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative blood loss</measure>
    <time_frame>Postoperative day 1</time_frame>
    <description>Postoperative blood (ml/kg) loss will be measured on the morning of postoperative day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for blood transfusion after surgery</measure>
    <time_frame>Up to 30 day after randomization</time_frame>
    <description>Number of patients who will need transfuion of any blood products (red cells, fresh frozen plasma, cryoprecipitate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraoperative myocardial ischemia</measure>
    <time_frame>Intraoperatively</time_frame>
    <description>The presence of intraoperative myocardial ischemia will be defined during continuous intraoperative ECG monitoring after calcium chloride or placebo administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial ischaemia on ECG after arrival to ICU</measure>
    <time_frame>Postoperative day 1</time_frame>
    <description>Number of patients who develop myocardial ischemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of alpha-amylase after surgery</measure>
    <time_frame>Postoperative day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Internal mammary artery vascular resistance (if available)</measure>
    <time_frame>Intraoperatively</time_frame>
    <description>Will be defined by intraoperative graft flow measurements</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">818</enrollment>
  <condition>Cardiac Surgery</condition>
  <condition>Cardiopulmonary Bypass</condition>
  <arm_group>
    <arm_group_label>Calcium chloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomly assigned to the experimental group will receive 15 mg/kg of calcium chloride (bolus) intravenously during separation from cardiopulmonary bypass</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0,9% Sodium Chloride</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomly assigned to the placebo group will receive equivalent amount of placebo intravenously during separation from cardiopulmonary bypass</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcium Chloride</intervention_name>
    <description>Calcium Chloride</description>
    <arm_group_label>Calcium chloride</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.9% Sodium Chloride</intervention_name>
    <description>0.9% Sodium Chloride</description>
    <arm_group_label>0,9% Sodium Chloride</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  surgery under cardiopulmonary bypass&#xD;
&#xD;
          -  valve or valve surgery + CABG&#xD;
&#xD;
          -  age &gt; 18 years&#xD;
&#xD;
          -  signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  emergency surgery&#xD;
&#xD;
          -  isolated aortic valve repair/replacement&#xD;
&#xD;
          -  planned (before surgery) blood transfusion&#xD;
&#xD;
          -  redo surgery&#xD;
&#xD;
          -  known allergy to the study drug&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  current enrollment into another RCT (in the last 30 days)&#xD;
&#xD;
          -  previous enrollment and randomization to ICARUS trial&#xD;
&#xD;
          -  liver cirrhosis (Child B or C)&#xD;
&#xD;
          -  transfusion during CPB&#xD;
&#xD;
          -  hypo- or hyperparathyreosis&#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_official>
    <last_name>Vladimir Lomivorotov</last_name>
    <role>Principal Investigator</role>
    <affiliation>Meshalkin Research Institute of Pathology of Circulation</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vladimir Lomivorotov, MD, PhD</last_name>
    <phone>83833476058</phone>
    <email>vvlom@mail.ru</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Vladimir Boboshko, MD, PhD</last_name>
    <email>vaboboshko@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sh. Mohammed Bin Khalifa Bin Salman Al-Khalifa Cardiac Center</name>
      <address>
        <city>Manama</city>
        <country>Bahrain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nazar Bukamal</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Federal Center for Cardiovascular Surgery</name>
      <address>
        <city>Astrakhan</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vadim Pasuga</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Federal Center for Cardiovascular Surgery</name>
      <address>
        <city>Chelyabinsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexander Turchaninov</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>District clinical hospital</name>
      <address>
        <city>Khanty-Mansiysk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dmitry Urusov</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>B.V. Petrovsky Russian Scientific Surgery Center</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boris Akselrod</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>M. Vladimirsky Moscow Regional Research Cinical Institute (MONIKI)</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexey Ovezov</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Meshalkin Research Institute of Pathology of Circulation</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630055</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vladimir Lomivorotov</last_name>
      <phone>3833476058</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Federal Center for Cardiovascular Surgery</name>
      <address>
        <city>Penza</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mikhail Evdokimov</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>St Petersburg University Multifunctional Clinical Centre</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sergey Efremov</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tomsk National Research Medical Center</name>
      <address>
        <city>Tomsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nikolay Kamenshikov</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>King Abdullah Medical City</name>
      <address>
        <city>Mecca</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Afifi</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Bahrain</country>
    <country>Russian Federation</country>
    <country>Saudi Arabia</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 9, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>January 25, 2021</last_update_submitted>
  <last_update_submitted_qc>January 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>inotropic support</keyword>
  <keyword>calcium chloride</keyword>
  <keyword>cardiopulmonary bypass</keyword>
  <keyword>cardiac surgery</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcium</mesh_term>
  </intervention_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/NCT03772990
org study id: 21/2019
nct id: NCT03772990
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Termination of cardiopulmonary bypass is a critical step in any cardiac surgical procedure
      and requires a thorough planning. Debate about rationale of calcium administration during
      weaning of cardiopulmonary bypass has been conducted for several decades; however, a
      consensus has not been yet reached.

      Perioperative hypocalcemia can develop because of haemodilution or calcium binding from
      heparin, albumin and citrate. Perioperative hypocalcemia is often complicated by development
      of arrhythmias, especially QT interval prolongation. Furthermore, low content of calcium can
      lead to vascular tone disorders, violation of neuromuscular transmission, altered hemostasis
      and heart failure, resistant to inotropic agents, especially in patients with concomitant
      cardiomyopathy.

      On the other hand, hypercalcaemia is a dangerous complication in cardiac surgery. Among the
      fatal, but rather rare complications, there are acute pancreatitis and the phenomenon of the
      "stone heart", which is essentially a reperfusion injury of the myocardium caused by rapid
      calcium overload. Hypercalcaemia can also trigger rhythm disturbances, hypertension, increase
      systemic vascular resistance, reduce diastolic compliance and impair relaxation of the
      myocardium due to excessive calcium intake into the cardiomyocytes, cause coronary vasospasm
      and aggravate ischaemic myocardial damage, impair arterial graft blood flow during
      aortocoronary and mammary coronary bypass surgery.

      To date, there is a lack of data indicating clinical efficacy of calcium administration
      before separation from CPB. Therefore, we designed this randomized controlled trial to test
      the hypothesis whether calcium administration at termination of CPB will reduce the need for
      inotropic support at the end of surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Inotropic support
time frame: Intraoperatively
description: Number of patients requiring inotropic support before transfer to intensive care unit
measure: Duration of inotropic support after surgery
time frame: 30 days after surgery
description: Duration of infusion of any vasoinotropic agent at any dose
measure: Vasoactive-inotropic score
time frame: Postoperative day 1
description: Vasoactive-inotropic score will be measured on the morning of postoperative day 1. The inotropic score will be calculated using the following formula: Dobutamine dose (in mcg/kg/min) + Dopamine dose (in mcg/kg/min) + Enoximone dose (in mcg/kg/min) + [Epinephrine dose (in mcg/kg/min) x 100] + [Norepinephrine dose (in mcg/kg/min) x 100].
measure: Plasma Ca2+ concentration before and after drug administration
time frame: Intraoperatively
measure: Time spent in theatre after cardiopulmonary bypass
time frame: Intraoperatively
measure: Duration of ventilation
time frame: Up to 30 day after randomization
measure: Duration of intensive care unit stay
time frame: Up to 30 day after randomization
measure: Myocardial infarction
time frame: Up to 30 day after randomization
description: Number of patients who develop myocardial infarction
measure: Atrial fibrillation
time frame: Up to 30 day after randomization
description: Number of patients who develop postoperative atrial fibrillation
measure: Type 1 and type 2 neurological complications
time frame: Up to 30 day after randomization
description: Number of patients who develop type 1 and type 2 develop myocardial infarction
measure: Postoperative blood loss
time frame: Postoperative day 1
description: Postoperative blood (ml/kg) loss will be measured on the morning of postoperative day 1
measure: Need for blood transfusion after surgery
time frame: Up to 30 day after randomization
description: Number of patients who will need transfuion of any blood products (red cells, fresh frozen plasma, cryoprecipitate)
measure: Intraoperative myocardial ischemia
time frame: Intraoperatively
description: The presence of intraoperative myocardial ischemia will be defined during continuous intraoperative ECG monitoring after calcium chloride or placebo administration
measure: Myocardial ischaemia on ECG after arrival to ICU
time frame: Postoperative day 1
description: Number of patients who develop myocardial ischemia
measure: Concentration of alpha-amylase after surgery
time frame: Postoperative day 1
measure: Internal mammary artery vascular resistance (if available)
time frame: Intraoperatively
description: Will be defined by intraoperative graft flow measurements
arm group label: Calcium chloride
arm group type: Experimental
description: Participants randomly assigned to the experimental group will receive 15 mg/kg of calcium chloride (bolus) intravenously during separation from cardiopulmonary bypass
arm group label: 0,9% Sodium Chloride
arm group type: Placebo Comparator
description: Participants randomly assigned to the placebo group will receive equivalent amount of placebo intravenously during separation from cardiopulmonary bypass
intervention type: Drug
intervention name: Calcium Chloride
description: Calcium Chloride
arm group label: Calcium chloride
intervention type: Drug
intervention name: 0.9% Sodium Chloride
description: 0.9% Sodium Chloride
arm group label: 0,9% Sodium Chloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vladimir Lomivorotov
role: Principal Investigator
affiliation: Meshalkin Research Institute of Pathology of Circulation
last name: Vladimir Lomivorotov, MD, PhD
phone: 83833476058
email: vvlom@mail.ru
last name: Vladimir Boboshko, MD, PhD
email: vaboboshko@gmail.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Bahrain
country: Russian Federation
country: Saudi Arabia
responsible party type: Sponsor
mesh term: Calcium
sharing ipd: Undecided