Clinical trial NCT03772990: Calcium Administration in Cardiac Surgery
Official title: Calcium Administration in Patients Undergoing Cardiac Surgery Under Cardiopulmonary Bypass (ICARUS Trial): Prospective Randomized, Double-blind Placebo-controlled Superiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cardiac Surgery
Cardiopulmonary Bypass
Keywords: inotropic support
calcium chloride
cardiopulmonary bypass
cardiac surgery
Lead sponsor: Meshalkin Research Institute of Pathology of Circulation
Sponsor class: NETWORK
Collaborators: name: Università Vita-Salute San Raffaele
First posted: 2018-12-12
Enrollment: 818
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Inotropic support
timeFrame: Intraoperatively
Secondary outcomes:
measure: Duration of inotropic support after surgery
timeFrame: 30 days after surgery
measure: Vasoactive-inotropic score
timeFrame: Postoperative day 1
measure: Plasma Ca2+ concentration before and after drug administration
timeFrame: Intraoperatively
measure: Time spent in theatre after cardiopulmonary bypass
timeFrame: Intraoperatively
measure: Duration of ventilation
timeFrame: Up to 30 day after randomization
measure: Duration of intensive care unit stay
timeFrame: Up to 30 day after randomization
measure: Myocardial infarction
timeFrame: Up to 30 day after randomization
measure: Atrial fibrillation
timeFrame: Up to 30 day after randomization
measure: Type 1 and type 2 neurological complications
timeFrame: Up to 30 day after randomization
measure: Postoperative blood loss
timeFrame: Postoperative day 1
measure: Need for blood transfusion after surgery
timeFrame: Up to 30 day after randomization
measure: Intraoperative myocardial ischemia
timeFrame: Intraoperatively
measure: Myocardial ischaemia on ECG after arrival to ICU
timeFrame: Postoperative day 1
measure: Concentration of alpha-amylase after surgery
timeFrame: Postoperative day 1
measure: Internal mammary artery vascular resistance (if available)
timeFrame: Intraoperatively
Other outcomes:
Locations:
city: Manama
country: Bahrain
facility: Sh. Mohammed Bin Khalifa Bin Salman Al-Khalifa Cardiac Center
city: Astrakhan
country: Russian Federation
facility: Federal Center for Cardiovascular Surgery
city: Chelyabinsk
country: Russian Federation
facility: Federal Center for Cardiovascular Surgery
city: Khanty-Mansiysk
country: Russian Federation
facility: District clinical hospital
city: Moscow
country: Russian Federation
facility: B.V. Petrovsky Russian Scientific Surgery Center
city: Moscow
country: Russian Federation
facility: M. Vladimirsky Moscow Regional Research Cinical Institute (MONIKI)
city: Novosibirsk
country: Russian Federation
facility: Meshalkin Research Institute of Pathology of Circulation
city: Penza
country: Russian Federation
facility: Federal Center for Cardiovascular Surgery
city: Saint Petersburg
country: Russian Federation
facility: St Petersburg University Multifunctional Clinical Centre
city: Tomsk
country: Russian Federation
facility: Tomsk National Research Medical Center
city: Mecca
country: Saudi Arabia
facility: King Abdullah Medical City
Study officials:
affiliation: Meshalkin Research Institute of Pathology of Circulation
name: Vladimir Lomivorotov
role: PRINCIPAL_INVESTIGATOR
References: