Miniaturized Extracorporeal Circulation Study

Aarhus University Hospital Skejby60 enrolled

Overview

Rationale: Contemporary coronary artery bypass grafting (CABG) continues to be associated with a significant risk of postoperative bleeding. Utilization of miniaturized extracorporeal circulation (miECC) significantly reduces the risk of postoperative bleeding but the underlying mechanisms are poorly understood. Primary Objective: To assess the impact of miECC compared to conventional extracorporeal circulation (cECC) on thrombin generation as indicator of the overall haemostatic capacity after CABG. Secondary Objectives To evaluate the impact of miECC versus cECC on blood loss and transfusion requirement, coagulation and fbrinolysis, inflammatory response, haemodilution and haemolysis, endorgan protection, seasibility and safety Study design: Single-center, double-blind, parallel-group randomized controlled trial Study population: 60 Patients undergoing non-emergent primary isolated CABG with ECC randomized 1:1 to receive either miECC or cECC

Blood samples will be obtained at the following time points: * T0; preoperative after induction of anaesthesia (after insertion of central venous line) * T1; after weaning of the ECC prior to protaminization * T2; 10 minutes after full protaminization * T3; six hours after the end of the ECC * T4; 1. postoperative day (16-20 hours following end of surgery)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Coronary Artery Disease

Interventions

CABGPROCEDURE

* Cannulation: 24-F arterial cannula, 29/29 F dual-stage venous cannula, and aortic root vent-/cardioplegia cannula * Grafting: pedicled left internal mammary artery, and no-touch * saphenous vein graft Heparin and protamine doses assessed by HMS Plus® Hemostasis Management System * Target activated coagulation time of \>400 seconds

Miniaturized extracorporeal circulationPROCEDURE

* Centrifugal pump to reduce mechanical stress * Circuit coated with biosurface to increase haemocompatibilty. * Ante- and retrograde autologous priming and low-volume cardioplegia solution (intermittend cold modified Calafiore) to minimize haemodilution * Collapsible soft-shell reservoir for blood volume management * Cell-saving device * Venous air removing device and electric clamp system to air embolism

Conventional extracorporeal circulationPROCEDURE

* Roller pump * Circuit uncoated * Hard-shell venous reservoir * Intermittend cold blood Harefield cardioplegia

Eligibility

Sex: ALLMin age: 40 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Non-emergent CABG with ECC * Current use of low-dose acetylsalicylic acid * Agreement of eligibility by the multidisciplinary heart team Exclusion Criteria: * Inability to give informed consent * Emergent treatment required (\< 24 hours) * Concomitant cardiac surgery * Previous cardiac surgery * Severely reduced kidney function (eGFR \< 30ml/min/1.73m2 or on dialysis) * Severely reduced ejection fraction (EF \< 45%) * Diagnosis of bleeding disorders * Non-aspirin antiplatelet drugs stopped \< 5 days preoperatively (Clopidogrel, Prasugrel, Ticagrelor, Ticlopidine) * Current use of systemic glucocorticoid therapy * Current use of vitamin K antagonists or new oral non-vitamin K anticoagulants * Platelet count \> 450 or \<100 x 109/l prior to surgery * Pregnant women or women of child bearing potential without negative pregnancy test * Active participant in any other intervention trial

Locations (1)

Dep. of Cardiothoracic Surgery, Aarhus University Hospital

Aarhus, Denmark

Outcomes

Primary Outcomes

Postoperative thrombin generation

Thrombin generation as a measure of the ability to generate thrombin in platelet poor plasma. Derived from the thrombogram

Time frame: up to 6 hours after CABG

Secondary Outcomes

Postoperative blood loss

Total output of mediastinal and pleural chest tubes

Time frame: up to 24 hours after CABG

Postoperative transfusion requirement

Transfusion of red blood cells, fresh frozen plasma, platelets

Time frame: up to 30 days after CABG

Fibrinolysis (Clot lysis, Fibrin D-dimer)

Clot lysis measured by dynamic turbidimetry

Time frame: up to 24 hours after CABG

Coagulation tests

* Platelet Count * aPTT * INR * Antithrombin * Fibrinogen * Prothrombin fragment 1+2

Time frame: up to 24 hours after CABG

Inflammatory response

* TNF-α * Interleukin panel * CRP white blood count

Time frame: up to 24 hours after CABG

Haemodilution (Nadir intraoperative haematocrit)

Measured in arterial blood samples

Time frame: up to 24 hours after CABG

Haemolysis (LDH)

Measured in lithium heparin plasma

Time frame: up to 24 hours postoperative

Postoperative CK-MB for myocardial injury

Measured in lithium heparin plasma

Time frame: up to 24 hours after CABG

-Intraoperative blood lactate for inadequate tissue perfusion

Measured in arterial blood samples

Time frame: up to 24 hours after CABG

Postoperative creatinine clearance for renal injury

Creatinine measured in lithium heparin plasma. eGFR calculated according to the CKD EPI Equation for Estimating GFR Expressed for Specified Race, Sex and Serum Creatinine (µmol/L)

Time frame: up to 30 days after CABG

-Perioperative myocardial infarction

defined according to the new definition of clinically relevant MI of the Society for Cardiovascular Angiography and Interventions

Time frame: 48 hours after CABG

-In-hospital neurological events (TCI/stroke)

verified by CT or MRI

Time frame: up to 30 days after CABG

-Postoperative requirement of renal replacement therapy

Continuous or intermittend renal replacement therapy

Time frame: up to 30 days after CABG

-Postoperative re-exploration for bleeding

Re-exploration due to excessive bleeding or haemodynamic instability

Time frame: up to 30 days after CABG

-Repeat revascularization

Defined as unplanned repeat PCI or CABG

Time frame: up to 30 days after CABG

-Length of ICU stay

Days of stay on ICU

Time frame: up to 30 days after CABG

-Duration of inotropic support

Hours of pharmacological or mechanical circulatory support

Time frame: up to 30 days after CABG

-Incidence of atrial fibrillation

Documented by telemetry or ECG

Time frame: up to 30 days after CABG

-Incidence of infection (requiring antibiotic therapy, wound revision for graft leg infection, superficial or deep sternal wound infection)

* Deep sternal wound infection * Wound revision for leg harvest surgical site infection * Requirement of antibiotic therapy

Time frame: up to 30 days after CABG

-Feasibility of miECC as measured by conversion to cECC and intraoperative complications

Serious adverse device events (air lock, dissection, bleeding that exceeds the capacity of the cell saver, air emboli, stop of the circuit, conversion to cECC) \- technical aspects (postoperative fluid gain (ml), venous drainage, visibility due to blood in the operative field, ability to maintain SvO2 \>65%)

Time frame: 24 hours

-30-day MACCE

* Death * MI * cerebrovascular accident * repeat revascularization

Time frame: up to 30 days after CABG

Acute kidney injury

Association of AKI with Neutrophil gelatinase associated lipocalin (NGAL) and renal risistive index (RRI)

Time frame: up to 7 days after intervention

Data from ClinicalTrials.gov

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