Miniaturized Extracorporeal Circulation Study

Study Overview
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Brief Summary
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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

Detailed Description
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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)

Official Title
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The Impact of Miniaturized Extracorporeal Circulation on Thrombin Generation and Postoperative Blood Loss

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Procedure: CABG
* Procedure: Miniaturized extracorporeal circulation
* Procedure: Conventional extracorporeal circulation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CABG with miniaturized ECC<br>Elective (CABG) with conventional miniaturized extracorporeal circulation (miECC) | Procedure: CABG<br>* 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<br>Procedure: Miniaturized extracorporeal circulation<br>* 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<br>|
| Active Comparator: CABG with conventional ECC<br>Elective CABG with conventional extracorporeal circulation (cECC) | Procedure: CABG<br>* 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<br>Procedure: Conventional extracorporeal circulation<br>* Roller pump Circuit uncoated Hard-shell venous reservoir Intermittend cold blood Harefield cardioplegia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative thrombin generation | Thrombin generation as a measure of the ability to generate thrombin in platelet poor plasma. Derived from the thrombogram | up to 6 hours after CABG | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative blood loss | Total output of mediastinal and pleural chest tubes | up to 24 hours after CABG | 
| Postoperative transfusion requirement | Transfusion of red blood cells, fresh frozen plasma, platelets | up to 30 days after CABG | 
| Fibrinolysis (Clot lysis, Fibrin D-dimer) | Clot lysis measured by dynamic turbidimetry | up to 24 hours after CABG | 
| Coagulation tests | Platelet Count aPTT INR Antithrombin Fibrinogen Prothrombin fragment 1+2 | up to 24 hours after CABG | 
| Inflammatory response | TNF-α Interleukin panel CRP white blood count | up to 24 hours after CABG | 
| Haemodilution (Nadir intraoperative haematocrit) | Measured in arterial blood samples | up to 24 hours after CABG | 
| Haemolysis (LDH) | Measured in lithium heparin plasma | up to 24 hours postoperative | 
| Postoperative CK-MB for myocardial injury | Measured in lithium heparin plasma | up to 24 hours after CABG | 
| -Intraoperative blood lactate for inadequate tissue perfusion | Measured in arterial blood samples | 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) | 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 | 48 hours after CABG | 
| -In-hospital neurological events (TCI/stroke) | verified by CT or MRI | up to 30 days after CABG | 
| -Postoperative requirement of renal replacement therapy | Continuous or intermittend renal replacement therapy | up to 30 days after CABG | 
| -Postoperative re-exploration for bleeding | Re-exploration due to excessive bleeding or haemodynamic instability | up to 30 days after CABG | 
| -Repeat revascularization | Defined as unplanned repeat PCI or CABG | up to 30 days after CABG | 
| -Length of ICU stay | Days of stay on ICU | up to 30 days after CABG | 
| -Duration of inotropic support | Hours of pharmacological or mechanical circulatory support | up to 30 days after CABG | 
| -Incidence of atrial fibrillation | Documented by telemetry or ECG | 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 | 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%) | 24 hours | 
| -30-day MACCE | Death MI cerebrovascular accident repeat revascularization | up to 30 days after CABG | 
| Acute kidney injury | Association of AKI with Neutrophil gelatinase associated lipocalin (NGAL) and renal risistive index (RRI) | up to 7 days after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery bypass grafting, Miniaturized extracorporeal circulation, Thrombin generation