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Calcium Administration in Cardiac Surgery (ICARUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03772990
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : February 19, 2020
Sponsor:
Collaborator:
Università Vita-Salute San Raffaele
Information provided by (Responsible Party):
Meshalkin Research Institute of Pathology of Circulation

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Cardiac Surgery Cardiopulmonary Bypass Drug: Calcium Chloride Drug: 0.9% Sodium Chloride Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 818 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Calcium Administration in Patients Undergoing Cardiac Surgery Under Cardiopulmonary Bypass (ICARUS Trial): Prospective Randomized, Double-blind Placebo-controlled Superiority Trial
Actual Study Start Date : January 14, 2019
Estimated Primary Completion Date : February 27, 2022
Estimated Study Completion Date : March 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Calcium chloride
Participants randomly assigned to the experimental group will receive 15 mg/kg of calcium chloride (bolus) intravenously during separation from cardiopulmonary bypass
Drug: Calcium Chloride
Calcium Chloride

Placebo Comparator: 0,9% Sodium Chloride
Participants randomly assigned to the placebo group will receive equivalent amount of placebo intravenously during separation from cardiopulmonary bypass
Drug: 0.9% Sodium Chloride
0.9% Sodium Chloride




Primary Outcome Measures :
  1. Inotropic support [ Time Frame: Intraoperatively ]
    Number of patients requiring inotropic support before transfer to intensive care unit


Secondary Outcome Measures :
  1. Duration of inotropic support after surgery [ Time Frame: 30 days after surgery ]
    Duration of infusion of any vasoinotropic agent at any dose

  2. Vasoactive-inotropic score [ Time Frame: Postoperative day 1 ]
    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].

  3. Plasma Ca2+ concentration before and after drug administration [ Time Frame: Intraoperatively ]
  4. Time spent in theatre after cardiopulmonary bypass [ Time Frame: Intraoperatively ]
  5. Duration of ventilation [ Time Frame: Up to 30 day after randomization ]
  6. Duration of intensive care unit stay [ Time Frame: Up to 30 day after randomization ]
  7. Myocardial infarction [ Time Frame: Up to 30 day after randomization ]
    Number of patients who develop myocardial infarction

  8. Atrial fibrillation [ Time Frame: Up to 30 day after randomization ]
    Number of patients who develop postoperative atrial fibrillation

  9. Type 1 and type 2 neurological complications [ Time Frame: Up to 30 day after randomization ]
    Number of patients who develop type 1 and type 2 develop myocardial infarction

  10. Postoperative blood loss [ Time Frame: Postoperative day 1 ]
    Postoperative blood (ml/kg) loss will be measured on the morning of postoperative day 1

  11. Need for blood transfusion after surgery [ Time Frame: Up to 30 day after randomization ]
    Number of patients who will need transfuion of any blood products (red cells, fresh frozen plasma, cryoprecipitate)

  12. Intraoperative myocardial ischemia [ Time Frame: Intraoperatively ]
    The presence of intraoperative myocardial ischemia will be defined during continuous intraoperative ECG monitoring after calcium chloride or placebo administration

  13. Myocardial ischaemia on ECG after arrival to ICU [ Time Frame: Postoperative day 1 ]
    Number of patients who develop myocardial ischemia

  14. Concentration of alpha-amylase after surgery [ Time Frame: Postoperative day 1 ]
  15. Internal mammary artery vascular resistance (if available) [ Time Frame: Intraoperatively ]
    Will be defined by intraoperative graft flow measurements



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • surgery under cardiopulmonary bypass
  • valve or valve surgery + CABG
  • age > 18 years
  • signed informed consent

Exclusion Criteria:

  • emergency surgery
  • isolated aortic valve repair/replacement
  • planned (before surgery) blood transfusion
  • redo surgery
  • known allergy to the study drug
  • pregnancy
  • current enrollment into another RCT (in the last 30 days)
  • previous enrollment and randomization to ICARUS trial
  • liver cirrhosis (Child B or C)
  • transfusion during CPB
  • hypo- or hyperparathyreosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03772990


Contacts
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Contact: Vladimir Lomivorotov, MD, PhD 83833476058 vvlom@mail.ru
Contact: Vladimir Shmyrev, MD, PhD shmyrevv@gmail.com

Locations
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Bahrain
Sh. Mohammed Bin Khalifa Bin Salman Al-Khalifa Cardiac Center Recruiting
Manama, Bahrain
Contact: Nazar Bukamal         
Russian Federation
Federal Center for Cardiovascular Surgery Recruiting
Astrakhan, Russian Federation
Contact: Vadim Pasuga         
Federal Center for Cardiovascular Surgery Recruiting
Chelyabinsk, Russian Federation
Contact: Alexander Turchaninov         
District clinical hospital Recruiting
Khanty-Mansiysk, Russian Federation
Contact: Dmitry Urusov         
B.V. Petrovsky Russian Scientific Surgery Center Recruiting
Moscow, Russian Federation
Contact: Boris Akselrod         
M. Vladimirsky Moscow Regional Research Cinical Institute (MONIKI) Recruiting
Moscow, Russian Federation
Contact: Alexey Ovezov         
Meshalkin Research Institute of Pathology of Circulation Recruiting
Novosibirsk, Russian Federation, 630055
Contact: Vladimir Lomivorotov    3833476058      
Federal Center for Cardiovascular Surgery Recruiting
Penza, Russian Federation
Contact: Mikhail Evdokimov         
St Petersburg University Multifunctional Clinical Centre Recruiting
Saint Petersburg, Russian Federation
Contact: Sergey Efremov         
Tomsk National Research Medical Center Recruiting
Tomsk, Russian Federation
Contact: Nikolay Kamenshikov         
Sponsors and Collaborators
Meshalkin Research Institute of Pathology of Circulation
Università Vita-Salute San Raffaele
Investigators
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Principal Investigator: Vladimir Lomivorotov Meshalkin Research Institute of Pathology of Circulation
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Responsible Party: Meshalkin Research Institute of Pathology of Circulation
ClinicalTrials.gov Identifier: NCT03772990    
Other Study ID Numbers: 21/2019
First Posted: December 12, 2018    Key Record Dates
Last Update Posted: February 19, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Meshalkin Research Institute of Pathology of Circulation:
inotropic support
calcium chloride
cardiopulmonary bypass
cardiac surgery
Additional relevant MeSH terms:
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Calcium
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs