Cardiac SurgeryTHROMBINNCT03347201
Thrombin Generation During Cardiopulmonary Bypass With Titrated Versus Conventional Anticoagulation Management.
A study testing HMS Plus in people with Cardiac Surgery, run by University Health Network, Toronto at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery
- What is being tested?
- HMS Plus
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 2 Oct 2017to 28 May 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Toronto General Hospital, University Health Network
Toronto, Ontario, M5G 2C4
About this study
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.
- Conditions
- Cardiac Surgery
- Being tested
- HMS Plus
- Keywords
- Cardiopulmonary bypass, Heparin, Protamine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMS PlusDevice
Subjects randomized to the intervention group will have their dose of Heparin and Protamine calculated by the HMS Plus.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group | Experimental | 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. Receives: Device: HMS Plus |
| Control Group | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Intra-operative
Secondary outcomes (5)
Rotational thromboelastometry (ROTEM)
Rotational thromboelastometry will be performed on the ROTEM delta instrument using citrated whole blood.
Measured: Intra-operative
Activated Clotting Time (ACT)
ACTs are performed during surgery
Measured: Intra-operative
Platelet Function Analysis (PFA)
PFA will be performed
Measured: Intra-operative
Blood loss
Amount of blood loss
Measured: Intraoperative day to the 7th postoperative day inclusive
Blood product transfusion
Collection of blood products transfused
Measured: Intraoperative day to the 7th postoperative day inclusive
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2017
- Study start2 Oct 2017
- Primary completion5 Mar 2019
- Study completion28 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jo Carroll, University Health Network, Toronto
- Investigators
- Keyvan Karkouti, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03347201
- Sponsor's protocol ID
- 15-9761
- Acronym
- THROMBIN
- Status last verified
- Dec 2020
- First submitted
- 12 Oct 2017
- Last updated
- 24 Dec 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thrombin Generation During Cardiopulmonary Bypass With Titrated Versus Conventional Anticoagulation Management.
- ClinicalTrials.gov ID
- NCT03347201
- Acronym / sponsor ID
- THROMBIN / 15-9761
- Conditions
- Cardiac Surgery
- Keywords
- Cardiopulmonary bypass, Heparin, Protamine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 2 Oct 2017 (actual)
- Primary completion
- 5 Mar 2019 (actual)
- Study completion
- 28 May 2019 (actual)
- First posted
- 20 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Group | Experimental | Device: HMS Plus1. 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. |
| Control Group | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMS PlusSubjects randomized to the intervention group will have their dose of Heparin and Protamine calculated by the HMS Plus. | Device | Intervention Group |
Primary outcome
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.
5 secondary outcomes
Rotational thromboelastometry (ROTEM)
Time frame: Intra-operative
Activated Clotting Time (ACT)
Time frame: Intra-operative
Platelet Function Analysis (PFA)
Time frame: Intra-operative
Blood loss
Time frame: Intraoperative day to the 7th postoperative day inclusive
Blood product transfusion
Time frame: Intraoperative day to the 7th postoperative day inclusive
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2020.
- Derived from this study: PubMed 35799088Li 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keyvan Karkouti, MD principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HMS Plus in people with Cardiac Surgery, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thrombin Generation (time frame: Intra-operative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03347201, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2020.