Thrombin Generation in Liver Transplant Surgery

April 29, 2021 updated by: University Health Network, Toronto

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • Toronto General Hospital - University Health Network
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All consenting adults undergoing liver transplantation surgery at Toronto General Hospital

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

- Patients who are unable to consent to the study or who refuse participation will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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 the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
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)
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)
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)
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)
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)
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)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
The platelet count from the complete blood count in x10^9/L
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
The international normalized ratio (INR) in seconds
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
The activated partial thromboplastin time (aPTT) in seconds
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
The Clauss Fibrinogen level in g/L
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
Rotational thromboelastometry (ROTEM)
The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Transfusion Outcomes - Red Blood Cells
Time Frame: From intra-operatively to within 12 hours post-operatively
The total number of red blood cells transfused
From intra-operatively to within 12 hours post-operatively
Transfusion Outcomes - Platelets
Time Frame: From intra-operatively to within 12 hours post-operatively
The total number of platelet units transfused
From intra-operatively to within 12 hours post-operatively
Transfusion Outcomes - Frozen Plasma
Time Frame: From intra-operatively to within 12 hours post-operatively
The total number of frozen plasma units transfused
From intra-operatively to within 12 hours post-operatively
Transfusion Outcomes - Prothrombin Complex Concentrate
Time Frame: From intra-operatively to within 12 hours post-operatively
The total number of units transfused
From intra-operatively to within 12 hours post-operatively
Transfusion Outcomes - Fibrinogen Concentrate
Time Frame: From intra-operatively to within 12 hours post-operatively
The total number of grams of fibrinogen transfused
From intra-operatively to within 12 hours post-operatively
Bleeding Outcomes - Delayed Abdominal Closure
Time Frame: From intra-operatively to within 12 hours post-operatively
Clinical bleeding outcome such as delayed abdominal
From intra-operatively to within 12 hours post-operatively
Bleeding Outcomes - Return to the Operating Room for Re-Exploration
Time Frame: From intra-operatively to within 12 hours post-operatively
Clinical bleeding outcome such as return to the operating room for re-exploration or evacuation of hematoma
From intra-operatively to within 12 hours post-operatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Justyna Bartoszko, MD MSc FRCPC, Toronto General Hospital - University Health Network
  • Principal Investigator: Keyvan Karkouti, MD MSc FRCPC, Toronto General Hospital - University Health Network

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 8, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 2, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 16, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 21, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 3, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20-5414.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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