Miniaturized Extracorporeal Circulation Study

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

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

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Procedure: CABG; Procedure: Miniaturized extracorporeal circulation; Procedure: Conventional extracorporeal circulation

Detailed Description

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
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Dep. of Cardiothoracic Surgery, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aarhus University Hospital Skejby
• Investigators: Principal Investigator: Ivy Susanne Modrau, MD, Dep. of Cardiothoracic Surgery, Aarhus University Hospital Skejby

Publications and helpful links

General Publications

• Modrau IS, Halle DR, Nielsen PH, Kimose HH, Greisen JR, Kremke M, Hvas AM. Impact of minimally invasive extracorporeal circulation on coagulation-a randomized trial. Eur J Cardiothorac Surg. 2020 Jun 1;57(6):1145-1153. doi: 10.1093/ejcts/ezaa010.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2017
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: July 8, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 13, 2017

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 6, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Coronary artery bypass grafting; Miniaturized extracorporeal circulation; Thrombin generation
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: 1-16-02-188-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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