Calcium Administration in Cardiac Surgery

Cardiac Surgery Clinical Trial

— ICARUS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03772990
• Other study ID #: 21/2019
• Status: Recruiting
• Phase: Phase 4
• Start date: January 14, 2019
• Est. completion date: March 30, 2022

Study information

• Verified date: January 2021
• Source: Meshalkin Research Institute of Pathology of Circulation
• Contact: Vladimir Lomivorotov, MD, PhD
• Phone: 83833476058
• Email: vvlom[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 818
• Est. completion date: March 30, 2022
• Est. primary completion date: February 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Surgery
• Cardiopulmonary Bypass

Intervention

Drug:
• Calcium Chloride
Calcium Chloride
• 0.9% Sodium Chloride
0.9% Sodium Chloride

Locations

Country	Name	City	State
Bahrain	Sh. Mohammed Bin Khalifa Bin Salman Al-Khalifa Cardiac Center	Manama
Russian Federation	Federal Center for Cardiovascular Surgery	Astrakhan
Russian Federation	Federal Center for Cardiovascular Surgery	Chelyabinsk
Russian Federation	District clinical hospital	Khanty-Mansiysk
Russian Federation	B.V. Petrovsky Russian Scientific Surgery Center	Moscow
Russian Federation	M. Vladimirsky Moscow Regional Research Cinical Institute (MONIKI)	Moscow
Russian Federation	Meshalkin Research Institute of Pathology of Circulation	Novosibirsk
Russian Federation	Federal Center for Cardiovascular Surgery	Penza
Russian Federation	St Petersburg University Multifunctional Clinical Centre	Saint Petersburg
Russian Federation	Tomsk National Research Medical Center	Tomsk
Saudi Arabia	King Abdullah Medical City	Mecca

Sponsors (2)

Lead Sponsor	Collaborator
Meshalkin Research Institute of Pathology of Circulation	Università Vita-Salute San Raffaele

Countries where clinical trial is conducted

Bahrain,  Russian Federation,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inotropic support	Number of patients requiring inotropic support before transfer to intensive care unit	Intraoperatively
Secondary	Duration of inotropic support after surgery	Duration of infusion of any vasoinotropic agent at any dose	30 days after surgery
Secondary	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
Secondary	Plasma Ca2+ concentration before and after drug administration		Intraoperatively
Secondary	Time spent in theatre after cardiopulmonary bypass		Intraoperatively
Secondary	Duration of ventilation		Up to 30 day after randomization
Secondary	Duration of intensive care unit stay		Up to 30 day after randomization
Secondary	Myocardial infarction	Number of patients who develop myocardial infarction	Up to 30 day after randomization
Secondary	Atrial fibrillation	Number of patients who develop postoperative atrial fibrillation	Up to 30 day after randomization
Secondary	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
Secondary	Postoperative blood loss	Postoperative blood (ml/kg) loss will be measured on the morning of postoperative day 1	Postoperative day 1
Secondary	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
Secondary	Intraoperative myocardial ischemia	The presence of intraoperative myocardial ischemia will be defined during continuous intraoperative ECG monitoring after calcium chloride or placebo administration	Intraoperatively
Secondary	Myocardial ischaemia on ECG after arrival to ICU	Number of patients who develop myocardial ischemia	Postoperative day 1
Secondary	Concentration of alpha-amylase after surgery		Postoperative day 1
Secondary	Internal mammary artery vascular resistance (if available)	Will be defined by intraoperative graft flow measurements	Intraoperatively