Thrombin Generation in Liver Transplant Surgery

Liver Transplantation Clinical Trial

Official title:

Diagnosis and Management of Impaired Thrombin Generation in Liver Transplant Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04762550
• Other study ID #: 20-5414.0
• Status: Recruiting
• Start date: March 8, 2021
• Est. completion date: January 1, 2022

Study information

• Verified date: February 2021
• Source: University Health Network, Toronto
• Contact: Justyna Bartoszko, MD MSc FRCPC
• Phone: 416-340-4800
• Email: justyna.bartoszko[@]uhn.ca
• Is FDA regulated: No
• Study type: Observational

Clinical 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 deficits and identify potential therapeutic targets. The clinical course of patients will be followed for major bleeding and transfusion outcomes.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 1, 2022
• Est. primary completion date: January 1, 2022
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blood Coagulation Disorder Due to Liver Disease
• Blood Coagulation Disorders
• Disease
• Hemostasis, Surgical
• Hemostatic Disorders
• Liver Diseases
• Liver Transplantation
• Thrombin

Locations

Country	Name	City	State
Canada	Toronto General Hospital - University Health Network	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Transfusion Outcomes - Red Blood Cells	The total number of red blood cells transfused	From intra-operatively to within 12 hours post-operatively
Other	Transfusion Outcomes - Platelets	The total number of platelet units transfused	From intra-operatively to within 12 hours post-operatively
Other	Transfusion Outcomes - Frozen Plasma	The total number of frozen plasma units transfused	From intra-operatively to within 12 hours post-operatively
Other	Transfusion Outcomes - Prothrombin Complex Concentrate	The total number of units transfused	From intra-operatively to within 12 hours post-operatively
Other	Transfusion Outcomes - Fibrinogen Concentrate	The total number of grams of fibrinogen transfused	From intra-operatively to within 12 hours post-operatively
Other	Bleeding Outcomes - Delayed Abdominal Closure	Clinical bleeding outcome such as delayed abdominal	From intra-operatively to within 12 hours post-operatively
Other	Bleeding Outcomes - Return to the Operating Room for Re-Exploration	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
Primary	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)	The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Primary	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)	The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Primary	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)	The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Primary	Thrombin Generation - Peak Height (nM)	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	Conventional Hemostatic Tests - Platelet Count	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
Secondary	Conventional Hemostatic Tests - INR	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
Secondary	Conventional Hemostatic Tests - aPTT	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
Secondary	Conventional Hemostatic Tests - Fibrinogen Level	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
Secondary	Viscoelastic Testing	Rotational thromboelastometry (ROTEM)	The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively