Liver TransplantationNCT04762550
Thrombin Generation in Liver Transplant Surgery
An observational study of Liver Transplantation and Thrombin, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This is a prospective observational study of 100 patients undergoing liver transplantation at a single centre. Thrombin generation and kinetics will be assessed using a novel point-of-care device, and compared to conventional measures of hemostasis as well as viscoelastic tests to pinpoint specific coagulation… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplantation, Thrombin, Hemostasis, Surgical
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 8 Mar 2021to 1 Jan 2022
- Phase
- Observational
- 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
- Adult, Older adult
Study population: All consenting adults undergoing liver transplantation surgery at Toronto General Hospital
Who may be able to join
- All adult patients (> 18 years of age) proceeding to imminent (within 24 hours) liver transplantation surgery at Toronto General Hospital will be offered participation.
- Patients should have end stage liver disease necessitating transplantation. All etiologies of end stage liver disease will be accepted.
Who cannot join
- Patients who are unable to consent to the study or who refuse participation will be excluded.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Toronto General Hospital - University Health Network
Toronto, Ontario, M5G 2C4
Justyna Bartoszko, MD MSc FRCPC, 416-340-3567, justyna.bartoszko@uhn.ca
About this study
Official title: Diagnosis and Management of Impaired Thrombin Generation in Liver Transplant Surgery
This is a prospective observational study of 100 patients undergoing liver transplantation at a single centre. Thrombin generation and kinetics will be assessed using a novel point-of-care device, and compared to conventional measures of hemostasis as well as viscoelastic tests to pinpoint specific coagulation deficits and identify potential therapeutic targets. The clinical course of patients will be followed for major bleeding and transfusion outcomes.
Read the detailed description
Liver transplantation is the only curative option for end stage liver disease, but is associated with high morbidity and mortality. End stage liver disease is known to be accompanied by dysregulated coagulation, which is further exacerbated in the immediate perioperative period by transplantation, leading to both coagulopathic bleeding and thrombosis. Altered thrombin generation is thought to play a key role in the predisposition of these patients for both severe coagulopathic hemorrhage and life-threatening thromboembolic complications. Despite this, thrombin generation during the immediate transplant period in patients with end-stage liver disease is poorly characterized, in part because it is not well reflected by conventional measures of coagulation. This study aims to characterize changes in thrombin generation capacity pre, intra- and post-transplant utilizing a novel point-of-care thrombin generation assay. Other specific aims of the study are to identify risk factors for patients with impaired thrombin generation and will assess the association of impaired thrombin generation with overall clinical bleeding risk. The overarching goal of this work is to develop a point-of-care-testing guided algorithm addressing dysregulated thrombin formation that improves coagulation management without increasing the risk of thromboembolic complications. Ultimately, this line of research will improve the outcomes of liver transplantation.
- Conditions
- Liver Transplantation, Thrombin, Hemostasis, Surgical, Blood Coagulation Disorder Due to Liver Disease, Blood Coagulation Disorders
- Medical subject headings
- Blood Coagulation Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients undergoing Liver Transplantation | This is a prospective observational study that intends to offer participation to all patients undergoing liver transplantation at Toronto General Hospital. Parameters that will be measured include Thrombin generation, viscoelastic testing utilizing ROTEM, and conventional laboratory testing (INR, aPTT and Fibrinogen level) at five time points: (a) Prior to cross-clamp application; (b) within the first 30 minutes of venous cross clamp removal; (c) after 30 minutes of reperfusion; (d) On arrival in the intensive care unit (ICU) or post-anesthesia recovery unit; and (5) 12 hours post-operatively. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thrombin Generation - Endogenous Thrombin Potential (nM*min)
The change in thrombin generation will be measured in patients undergoing liver transplantation, as assessed through the Endogenous Thrombin Potential (nM*min)
Measured: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Thrombin Generation - Lag Time (Seconds)
The change in thrombin generation will be measured in patients undergoing liver transplantation as assessed by the Lag Time (Seconds)
Measured: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Thrombin Generation - Time to Peak (Seconds)
The change in thrombin generation will be measured in patients undergoing liver transplantation by the Time to Peak (Seconds)
Measured: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Thrombin Generation - Peak Height (nM)
The change in thrombin generation will be measured in patients undergoing liver transplantation by the Peak Height (nM)
Measured: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Secondary outcomes (5)
Conventional Hemostatic Tests - Platelet Count
The platelet count from the complete blood count in x10^9/L
Measured: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Conventional Hemostatic Tests - INR
The international normalized ratio (INR) in seconds
Measured: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Conventional Hemostatic Tests - aPTT
The activated partial thromboplastin time (aPTT) in seconds
Measured: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Conventional Hemostatic Tests - Fibrinogen Level
The Clauss Fibrinogen level in g/L
Measured: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Viscoelastic Testing
Rotational thromboelastometry (ROTEM)
Measured: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start8 Mar 2021
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Justyna Bartoszko, MD MSc FRCPC, Principal investigator, Toronto General Hospital - University Health NetworkKeyvan Karkouti, MD MSc FRCPC, Principal investigator, Toronto General Hospital - University Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04762550
- Sponsor's protocol ID
- 20-5414.0
- Status last verified
- Feb 2021
- First submitted
- 2 Feb 2021
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnosis and Management of Impaired Thrombin Generation in Liver Transplant Surgery
- ClinicalTrials.gov ID
- NCT04762550
- Acronym / sponsor ID
- 20-5414.0
- Conditions
- Liver Transplantation, Thrombin, Hemostasis, Surgical, Blood Coagulation Disorder Due to Liver Disease, Blood Coagulation Disorders
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 21 Feb 2021 (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.
This is a prospective observational study of 100 patients undergoing liver transplantation at a single centre. Thrombin generation and kinetics will be assessed using a novel point-of-care device, and compared to conventional measures of hemostasis as well as viscoelastic tests to pinpoint specific coagulation deficits and identify potential therapeutic targets. The clinical course of patients will be followed for major bleeding and transfusion outcomes.
Detailed description
Liver transplantation is the only curative option for end stage liver disease, but is associated with high morbidity and mortality. End stage liver disease is known to be accompanied by dysregulated coagulation, which is further exacerbated in the immediate perioperative period by transplantation, leading to both coagulopathic bleeding and thrombosis. Altered thrombin generation is thought to play a key role in the predisposition of these patients for both severe coagulopathic hemorrhage and life-threatening thromboembolic complications. Despite this, thrombin generation during the immediate transplant period in patients with end-stage liver disease is poorly characterized, in part because it is not well reflected by conventional measures of coagulation. This study aims to characterize changes in thrombin generation capacity pre, intra- and post-transplant utilizing a novel point-of-care thrombin generation assay. Other specific aims of the study are to identify risk factors for patients with impaired thrombin generation and will assess the association of impaired thrombin generation with overall clinical bleeding risk. The overarching goal of this work is to develop a point-of-care-testing guided algorithm addressing dysregulated thrombin formation that improves coagulation management without increasing the risk of thromboembolic complications. Ultimately, this line of research will improve the outcomes of liver transplantation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients undergoing Liver Transplantation | – | –This is a prospective observational study that intends to offer participation to all patients undergoing liver transplantation at Toronto General Hospital. Parameters that will be measured include Thrombin generation, viscoelastic testing utilizing ROTEM, and conventional laboratory testing (INR, aPTT and Fibrinogen level) at five time points: (a) Prior to cross-clamp application; (b) within the first 30 minutes of venous cross clamp removal; (c) after 30 minutes of reperfusion; (d) On arrival in the intensive care unit (ICU) or post-anesthesia recovery unit; and (5) 12 hours post-operatively. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- All consenting adults undergoing liver transplantation surgery at Toronto General Hospital
Key inclusion criteria (2 listed)
- All adult patients (> 18 years of age) proceeding to imminent (within 24 hours) liver transplantation surgery at Toronto General Hospital will be offered participation.
- Patients should have end stage liver disease necessitating transplantation. All etiologies of end stage liver disease will be accepted.
Key exclusion criteria (1 listed)
- Patients who are unable to consent to the study or who refuse participation will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Thrombin Generation - Endogenous Thrombin Potential (nM*min)
Time frame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
The change in thrombin generation will be measured in patients undergoing liver transplantation, as assessed through the Endogenous Thrombin Potential (nM*min)
Thrombin Generation - Lag Time (Seconds)
Time frame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
The change in thrombin generation will be measured in patients undergoing liver transplantation as assessed by the Lag Time (Seconds)
Thrombin Generation - Time to Peak (Seconds)
Time frame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
The change in thrombin generation will be measured in patients undergoing liver transplantation by the Time to Peak (Seconds)
Thrombin Generation - Peak Height (nM)
Time frame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
The change in thrombin generation will be measured in patients undergoing liver transplantation by the Peak Height (nM)
5 secondary outcomes
Conventional Hemostatic Tests - Platelet Count
Time frame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Conventional Hemostatic Tests - INR
Time frame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Conventional Hemostatic Tests - aPTT
Time frame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Conventional Hemostatic Tests - Fibrinogen Level
Time frame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Viscoelastic Testing
Time frame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Individual participant dataSharing planned: No
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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.
Justyna Bartoszko, MD MSc FRCPC principal investigator
Toronto General Hospital - University Health Network
Keyvan Karkouti, MD MSc FRCPC principal investigator
Toronto General Hospital - University Health Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Transplantation and Thrombin, 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 2 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 3 May 2021. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Justyna Bartoszko, MD MSc FRCPC (416-340-4800 ext. 3243, justyna.bartoszko@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thrombin Generation - Endogenous Thrombin Potential (nM*min) (time frame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 May 2021.