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Calcium Administration in Cardiac Surgery (ICARUS)

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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

Tracking Information
First Submitted Date  ICMJE December 7, 2018
First Posted Date  ICMJE December 12, 2018
Last Update Posted Date February 19, 2020
Actual Study Start Date  ICMJE January 14, 2019
Estimated Primary Completion Date February 27, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2018)
Inotropic support [ Time Frame: Intraoperatively ]
Number of patients requiring inotropic support before transfer to intensive care unit
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2018)
  • Duration of inotropic support after surgery [ Time Frame: 30 days after surgery ]
    Duration of infusion of any vasoinotropic agent at any dose
  • 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].
  • Plasma Ca2+ concentration before and after drug administration [ Time Frame: Intraoperatively ]
  • Time spent in theatre after cardiopulmonary bypass [ Time Frame: Intraoperatively ]
  • Duration of ventilation [ Time Frame: Up to 30 day after randomization ]
  • Duration of intensive care unit stay [ Time Frame: Up to 30 day after randomization ]
  • Myocardial infarction [ Time Frame: Up to 30 day after randomization ]
    Number of patients who develop myocardial infarction
  • Atrial fibrillation [ Time Frame: Up to 30 day after randomization ]
    Number of patients who develop postoperative atrial fibrillation
  • 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
  • Postoperative blood loss [ Time Frame: Postoperative day 1 ]
    Postoperative blood (ml/kg) loss will be measured on the morning of postoperative day 1
  • 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)
  • 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
  • Myocardial ischaemia on ECG after arrival to ICU [ Time Frame: Postoperative day 1 ]
    Number of patients who develop myocardial ischemia
  • Concentration of alpha-amylase after surgery [ Time Frame: Postoperative day 1 ]
  • Internal mammary artery vascular resistance (if available) [ Time Frame: Intraoperatively ]
    Will be defined by intraoperative graft flow measurements
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2018)
  • Duration of inotropic support after surgery [ Time Frame: 30 days after surgery ]
    Duration of infusion of any vasoinotropic agent at any dose
  • Vasoactive-inotropic score [ Time Frame: Postoperative day 1 ]
    Vasoactive-inotropic score will be measured on the morning of postoperative day 1
  • Plasma Ca2+ concentration before and after drug administration [ Time Frame: Intraoperatively ]
  • Time spent in theatre after cardiopulmonary bypass [ Time Frame: Intraoperatively ]
  • Duration of ventilation [ Time Frame: Up to 30 day after randomization ]
  • Duration of intensive care unit stay [ Time Frame: Up to 30 day after randomization ]
  • Myocardial infarction [ Time Frame: Up to 30 day after randomization ]
  • Atrial fibrillation [ Time Frame: Up to 30 day after randomization ]
  • Type 1 and type 2 neurological complications [ Time Frame: Up to 30 day after randomization ]
  • Postoperative blood loss [ Time Frame: Postoperative day 1 ]
    Postoperative blood loss will be measured on the morning of postoperative day 1
  • Need for blood transfusion after surgery [ Time Frame: Up to 30 day after randomization ]
  • 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
  • Myocardial ischaemia on ECG after arrival to ICU [ Time Frame: Postoperative day 1 ]
  • Concentration of alpha-amylase after surgery [ Time Frame: Postoperative day 1 ]
  • Internal mammary artery vascular resistance (if available) [ Time Frame: Intraoperatively ]
    Will be defined by intraoperative graft flow measurements
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Calcium Administration in Cardiac Surgery
Official Title  ICMJE Calcium Administration in Patients Undergoing Cardiac Surgery Under Cardiopulmonary Bypass (ICARUS Trial): Prospective Randomized, Double-blind Placebo-controlled Superiority Trial
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cardiac Surgery
  • Cardiopulmonary Bypass
Intervention  ICMJE
  • Drug: Calcium Chloride
    Calcium Chloride
  • Drug: 0.9% Sodium Chloride
    0.9% Sodium Chloride
Study Arms  ICMJE
  • 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
    Intervention: Drug: 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
    Intervention: Drug: 0.9% Sodium Chloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 9, 2018)
818
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2022
Estimated Primary Completion Date February 27, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vladimir Lomivorotov, MD, PhD 83833476058 vvlom@mail.ru
Contact: Vladimir Shmyrev, MD, PhD shmyrevv@gmail.com
Listed Location Countries  ICMJE Bahrain,   Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03772990
Other Study ID Numbers  ICMJE 21/2019
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Meshalkin Research Institute of Pathology of Circulation
Study Sponsor  ICMJE Meshalkin Research Institute of Pathology of Circulation
Collaborators  ICMJE Università Vita-Salute San Raffaele
Investigators  ICMJE
Principal Investigator: Vladimir Lomivorotov Meshalkin Research Institute of Pathology of Circulation
PRS Account Meshalkin Research Institute of Pathology of Circulation
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP