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CompletedNCT03347201THROMBINUpdated Dec 24, 2020

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

An interventional study of HMS Plus in Cardiac Surgery, sponsored by University Health Network, Toronto. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-12-24.

Sponsored by University Health Network, Toronto · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cardiac Surgery

Keywords

  • Cardiopulmonary bypass, Heparin, Protamine
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
100 participants (actual)

Study arms

  • 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

  • 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.

Interventions

  • DeviceHMS Plus

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

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Intra-operative

Secondary outcomes

  1. Rotational thromboelastometry (ROTEM)

    Rotational thromboelastometry will be performed on the ROTEM delta instrument using citrated whole blood.

    Time frame: Intra-operative

  2. Activated Clotting Time (ACT)

    ACTs are performed during surgery

    Time frame: Intra-operative

  3. Platelet Function Analysis (PFA)

    PFA will be performed

    Time frame: Intra-operative

  4. Blood loss

    Amount of blood loss

    Time frame: Intraoperative day to the 7th postoperative day inclusive

  5. Blood product transfusion

    Collection of blood products transfused

    Time frame: Intraoperative day to the 7th postoperative day inclusive

06

Study locations

1 site
  • Toronto General Hospital, University Health Network
    Toronto, Ontario M5G 2C4, Canada
07

References and documents

Publications

  • 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. PubMed 35799088 ↗
08

Registry details

Key details

Study ID
NCT03347201
Lead sponsor
University Health Network, Toronto
Responsible party
Jo Carroll (Manager Anesthesia Research, University Health Network, Toronto) — Principal investigator
First posted
Nov 20, 2017
Start date
Oct 2, 2017
Primary completion
Mar 5, 2019
Completion
May 28, 2019
Last update
Dec 24, 2020

Study contacts

Keyvan Karkouti, MD
principal investigator · University Health Network, Toronto

Oversight

FDA-regulated drug
No
FDA-regulated device
No
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