Thrombin Generation During Cardiopulmonary Bypass With Titrated Versus Conventional Anticoagulation Management.

Cardiac Surgery Clinical Trial

— THROMBIN  

Official title:

Thrombin Generation During Cardiopulmonary Bypass With Titrated Versus Conventional Anticoagulation Management.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03347201
• Other study ID #: 15-9761
• Status: Completed
• Phase: N/A
• Start date: October 2, 2017
• Est. completion date: May 28, 2019

Study information

• Verified date: December 2020
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 28, 2019
• Est. primary completion date: March 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Surgery

Intervention

Device:
• HMS Plus
Subjects randomized to the intervention group will have their dose of Heparin and Protamine calculated by the HMS Plus.

Locations

Country	Name	City	State
Canada	Toronto General Hospital, University Health Network	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombin Generation	The primary outcomes will be thrombin generation potential assessed via peak thrombin and endogenous thrombin potential on CAT thrombograms of plasma samples taken before, during and after cardiopulmonary bypass.	Intra-operative
Secondary	Rotational thromboelastometry (ROTEM)	Rotational thromboelastometry will be performed on the ROTEM delta instrument using citrated whole blood.	Intra-operative
Secondary	Activated Clotting Time (ACT)	ACTs are performed during surgery	Intra-operative
Secondary	Platelet Function Analysis (PFA)	PFA will be performed	Intra-operative
Secondary	Blood loss	Amount of blood loss	Intraoperative day to the 7th postoperative day inclusive
Secondary	Blood product transfusion	Collection of blood products transfused	Intraoperative day to the 7th postoperative day inclusive