Clinical trial NCT03347201: Thrombin Generation During Cardiopulmonary Bypass With Titrated Versus Conventional Anticoagulation Management.
Official title: Thrombin Generation During Cardiopulmonary Bypass With Titrated Versus Conventional Anticoagulation Management.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiac Surgery
Keywords: Cardiopulmonary bypass, Heparin, Protamine
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2017-11-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In this study, the investigators will be comparing anticoagulation for Cardiopulmonary Bypass (CPB) guided by the Hemostasis Management System (HMS Plus) with the current dosing based on weight and ACT measurements.

The primary objective of this study is to determine whether relative to patients with conventional management, those managed with the HMS Plus have improved thrombin generation after CPB.

The secondary objective is to determine if patients in the HMS Plus group have reduced blood loss in the first 24 hours following surgery compared with patients in the conventional group.

Detailed description: Cardiopulmonary bypass (CPB) allows cardiac surgery to be performed on a motionless, bloodless heart while maintaining circulation to the rest of the body. Anticoagulation with heparin prevents the body's clotting system from being activated when blood comes into contact with the walls of the bypass circuit. The amount of heparin given to achieve this effect is determined on a weight-based dosing and monitored with a point-of-care monitor called ACT (activated clotting time). However, there remains a high level of variability in the concentration of heparin in the blood and the ACT is affected by hypothermia and dilution of the blood, both of which commonly occur during CPB for cardiac surgery.

The Hemostasis Management System (HMS Plus) offers an alternative way of dosing and monitoring heparin by aiming to achieve a pre-determined heparin concentration throughout CPB, rather than being determined by the ACT. It also aims to determine the dose of protamine, the drug used to reverse heparin at the end CPB, required based on residual heparin concentration rather than on a 1:1 ratio of the total dose of heparin given which is the common current practice. The benefits of using this system are proposed to be more effective anticoagulation during CPB meaning less of the body's reserves of clotting factors are consumed. This could mean potentially less bleeding and decrease requirement of blood products following surgery.

Eligibility criteria: Inclusion Criteria:

* Scheduled to undergo non-emergent coronary artery bypass grafting, valve repair or replacement (with or without ascending aortic replacement) or a combination of these procedures requiring the use of CPB

Exclusion Criteria:

* Less than 18 years old
* Planned use of deep hypothermic circulatory arrest
* Cases where use of brief circulatory arrest anticipated
* Highly complex cases (LVAD, Heart Transplant, Complex congenital)
* Significant liver dysfunction (liver enzymes \> 2-fold higher than upper limit of normal
* Pre-existing coagulopathy (INR \>1.5, PTT \>45 seconds, fibrinogen \< 1.0g/L, platelet count \<100x109/L)
* Use of long acting oral anticoagulants
* Patients on heparin infusions pre-operatively
* Major hemoglobinopathies, thalassemia or iron storage diseases
* Previous diagnosis of HIT
* Lack of informed consent

Primary outcomes:
measure: Thrombin Generation
timeFrame: Intra-operative
Secondary outcomes:
measure: Rotational thromboelastometry (ROTEM)
timeFrame: Intra-operative
measure: Activated Clotting Time (ACT)
timeFrame: Intra-operative
measure: Platelet Function Analysis (PFA)
timeFrame: Intra-operative
measure: Blood loss
timeFrame: Intraoperative day to the 7th postoperative day inclusive
measure: Blood product transfusion
timeFrame: Intraoperative day to the 7th postoperative day inclusive
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Keyvan Karkouti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li H, Bartoszko J, Serrick C, Rao V, Karkouti K. Titrated versus conventional anticoagulation management for thrombin generation in cardiac surgery: a randomized controlled trial. Can J Anaesth. 2022 Sep;69(9):1117-1128. doi: 10.1007/s12630-022-02278-1. Epub 2022 Jul 8.