Clinical trial NCT03216720: Miniaturized Extracorporeal Circulation Study
Official title: The Impact of Miniaturized Extracorporeal Circulation on Thrombin Generation and Postoperative Blood Loss
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Coronary artery bypass grafting
Miniaturized extracorporeal circulation
Thrombin generation
Lead sponsor: Aarhus University Hospital Skejby
Sponsor class: OTHER
First posted: 2017-07-13
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Postoperative thrombin generation
timeFrame: up to 6 hours after CABG
Secondary outcomes:
measure: Postoperative blood loss
timeFrame: up to 24 hours after CABG
measure: Postoperative transfusion requirement
timeFrame: up to 30 days after CABG
measure: Fibrinolysis (Clot lysis, Fibrin D-dimer)
timeFrame: up to 24 hours after CABG
measure: Coagulation tests
timeFrame: up to 24 hours after CABG
measure: Inflammatory response
timeFrame: up to 24 hours after CABG
measure: Haemodilution (Nadir intraoperative haematocrit)
timeFrame: up to 24 hours after CABG
measure: Haemolysis (LDH)
timeFrame: up to 24 hours postoperative
measure: Postoperative CK-MB for myocardial injury
timeFrame: up to 24 hours after CABG
measure: -Intraoperative blood lactate for inadequate tissue perfusion
timeFrame: up to 24 hours after CABG
measure: Postoperative creatinine clearance for renal injury
timeFrame: up to 30 days after CABG
measure: -Perioperative myocardial infarction
timeFrame: 48 hours after CABG
measure: -In-hospital neurological events (TCI/stroke)
timeFrame: up to 30 days after CABG
measure: -Postoperative requirement of renal replacement therapy
timeFrame: up to 30 days after CABG
measure: -Postoperative re-exploration for bleeding
timeFrame: up to 30 days after CABG
measure: -Repeat revascularization
timeFrame: up to 30 days after CABG
measure: -Length of ICU stay
timeFrame: up to 30 days after CABG
measure: -Duration of inotropic support
timeFrame: up to 30 days after CABG
measure: -Incidence of atrial fibrillation
timeFrame: up to 30 days after CABG
measure: -Incidence of infection (requiring antibiotic therapy, wound revision for graft leg infection, superficial or deep sternal wound infection)
timeFrame: up to 30 days after CABG
measure: -Feasibility of miECC as measured by conversion to cECC and intraoperative complications
timeFrame: 24 hours
measure: -30-day MACCE
timeFrame: up to 30 days after CABG
measure: Acute kidney injury
timeFrame: up to 7 days after intervention
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Dep. of Cardiothoracic Surgery, Aarhus University Hospital
Study officials:
affiliation: Dep. of Cardiothoracic Surgery, Aarhus University Hospital Skejby
name: Ivy Susanne Modrau, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.