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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03347201
Recruitment Status : Active, not recruiting
First Posted : November 20, 2017
Last Update Posted : December 16, 2019
Information provided by (Responsible Party):
Jo Carroll, University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Cardiac Surgery Device: HMS Plus Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Thrombin Generation During Cardiopulmonary Bypass With Titrated Versus Conventional Anticoagulation Management.
Actual Study Start Date : October 2, 2017
Actual Primary Completion Date : March 5, 2019
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Intervention Group
  1. Initial heparin bolus before CPB to be calculated using HMS Plus.
  2. Following commencement of CPB further heparin requirements will be determined using the HMS Plus. ACT's will also be checked whilst on CPB and if falls below 480 seconds, additional heparin will also be given.
  3. Following cessation of CPB the dose of protamine required to reverse residual heparin will be calculated using the HMS Plus.
Device: HMS Plus
Subjects randomized to the intervention group will have their dose of Heparin and Protamine calculated by the HMS Plus.

No Intervention: Control Group
Patients in the control arm will undergo routine heparin anticoagulation using a weight based initial dose of 400 units/kg, aiming for an ACT of >480 seconds. Further heparin doses (5000 to 10000 units) will be given if the ACT falls below 480 seconds whilst on bypass. At the end of CPB heparin will be reversed with protamine using 1:1 ratio based on the initial dose of heparin given pre-bypass. HMS Plus measures will also be conducted in this group for study purposes, but the results will not be made available to the clinicians.

Primary Outcome Measures :
  1. Thrombin Generation [ Time Frame: Intra-operative ]
    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.

Secondary Outcome Measures :
  1. Rotational thromboelastometry (ROTEM) [ Time Frame: Intra-operative ]
    Rotational thromboelastometry will be performed on the ROTEM delta instrument using citrated whole blood.

  2. Activated Clotting Time (ACT) [ Time Frame: Intra-operative ]
    ACTs are performed during surgery

  3. Platelet Function Analysis (PFA) [ Time Frame: Intra-operative ]
    PFA will be performed

  4. Blood loss [ Time Frame: Intraoperative day to the 7th postoperative day inclusive ]
    Amount of blood loss

  5. Blood product transfusion [ Time Frame: Intraoperative day to the 7th postoperative day inclusive ]
    Collection of blood products transfused

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03347201

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Canada, Ontario
Toronto General Hospital, University Health Network
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
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Principal Investigator: Keyvan Karkouti, MD University Health Network, Toronto
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Responsible Party: Jo Carroll, Manager Anesthesia Research, University Health Network, Toronto Identifier: NCT03347201    
Other Study ID Numbers: 15-9761
First Posted: November 20, 2017    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jo Carroll, University Health Network, Toronto:
Cardiopulmonary bypass, Heparin, Protamine