Calcium Administration in Cardiac Surgery (ICARUS)

Calcium Administration in Patients Undergoing Cardiac Surgery Under Cardiopulmonary Bypass (ICARUS Trial): Prospective Randomized, Double-blind Placebo-controlled Superiority Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Surgery; Cardiopulmonary Bypass
• Intervention / Treatment: Drug: Calcium Chloride; Drug: 0.9% Sodium Chloride

• Study Type: Interventional
• Enrollment (Anticipated): 818
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Vladimir Lomivorotov, MD, PhD; Phone Number: 83833476058; Email: vvlom@mail.ru
• Study Contact Backup: Name: Vladimir Boboshko, MD, PhD; Email: vaboboshko@gmail.com

Study Locations

• Bahrain
  • Manama, Bahrain
    • Recruiting
    • Sh. Mohammed Bin Khalifa Bin Salman Al-Khalifa Cardiac Center
    • Contact: Nazar Bukamal
• Russian Federation
  • Astrakhan, Russian Federation
    • Recruiting
    • Federal Center for Cardiovascular Surgery
    • Contact: Vadim Pasuga
  • Chelyabinsk, Russian Federation
    • Recruiting
    • Federal Center for Cardiovascular Surgery
    • Contact: Alexander Turchaninov
  • Khanty-Mansiysk, Russian Federation
    • Recruiting
    • District Clinical Hospital
    • Contact: Dmitry Urusov
  • Moscow, Russian Federation
    • Recruiting
    • B.V. Petrovsky Russian Scientific Surgery Center
    • Contact: Boris Akselrod
  • Moscow, Russian Federation
    • Recruiting
    • M. Vladimirsky Moscow Regional Research Cinical Institute (MONIKI)
    • Contact: Alexey Ovezov
  • Novosibirsk, Russian Federation, 630055
    • Recruiting
    • Meshalkin Research Institute of Pathology of Circulation
    • Contact: Vladimir Lomivorotov; Phone Number: 3833476058
  • Penza, Russian Federation
    • Recruiting
    • Federal Center for Cardiovascular Surgery
    • Contact: Mikhail Evdokimov
  • Saint Petersburg, Russian Federation
    • Recruiting
    • St Petersburg University Multifunctional Clinical Centre
    • Contact: Sergey Efremov
  • Tomsk, Russian Federation
    • Recruiting
    • Tomsk National Research Medical Center
    • Contact: Nikolay Kamenshikov
• Saudi Arabia
  • Mecca, Saudi Arabia
    • Recruiting
    • King Abdullah Medical City
    • Contact: Sarah Afifi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inotropic support	Number of patients requiring inotropic support before transfer to intensive care unit	Intraoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of inotropic support after surgery	Duration of infusion of any vasoinotropic agent at any dose	30 days after surgery
Vasoactive-inotropic score	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].	Postoperative day 1
Plasma Ca2+ concentration before and after drug administration		Intraoperatively
Time spent in theatre after cardiopulmonary bypass		Intraoperatively
Duration of ventilation		Up to 30 day after randomization
Duration of intensive care unit stay		Up to 30 day after randomization
Myocardial infarction	Number of patients who develop myocardial infarction	Up to 30 day after randomization
Atrial fibrillation	Number of patients who develop postoperative atrial fibrillation	Up to 30 day after randomization
Type 1 and type 2 neurological complications	Number of patients who develop type 1 and type 2 develop myocardial infarction	Up to 30 day after randomization
Postoperative blood loss	Postoperative blood (ml/kg) loss will be measured on the morning of postoperative day 1	Postoperative day 1
Need for blood transfusion after surgery	Number of patients who will need transfuion of any blood products (red cells, fresh frozen plasma, cryoprecipitate)	Up to 30 day after randomization
Intraoperative myocardial ischemia	The presence of intraoperative myocardial ischemia will be defined during continuous intraoperative ECG monitoring after calcium chloride or placebo administration	Intraoperatively
Myocardial ischaemia on ECG after arrival to ICU	Number of patients who develop myocardial ischemia	Postoperative day 1
Concentration of alpha-amylase after surgery		Postoperative day 1
Internal mammary artery vascular resistance (if available)	Will be defined by intraoperative graft flow measurements	Intraoperatively

Collaborators and Investigators

• Sponsor: Meshalkin Research Institute of Pathology of Circulation
• Collaborators: Università Vita-Salute San Raffaele
• Investigators: Principal Investigator: Vladimir Lomivorotov, Meshalkin Research Institute of Pathology of Circulation

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2019
• Primary Completion (Anticipated): February 27, 2022
• Study Completion (Anticipated): March 30, 2022

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 9, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: cardiac surgery; cardiopulmonary bypass; inotropic support; calcium chloride
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: 21/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No