Tranexamic Acid Versus Placebo for Blood to Reduce Perioperative Bleeding Post-liver Resection

Study Overview
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Brief Summary
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Tranexamic acid (TXA) is an antifibrinolytic agent that has been shown to reduce blood loss and blood transfusion requirements in the following patient populations: multisystem trauma, liver transplantation, cardiac surgery and spine surgery. Patients undergoing major liver resection are at risk of severe perioperative blood loss and may also benefit from perioperative TXA administration. This open label, non-randomized study to evaluate the pharmacokinetic and pharmacodynamic properties of two well studied dosing regimens of TXA will provide guidance in determining the optimal TXA dosing regimen for patients undergoing major liver resection. Compelling evidence of the effectiveness of TXA comes from the large multicentred, multi-national CRASH-2 trial where TXA was administered as a 1 g bolus + 1 g infusion over 8 hours. In liver transplant surgery, the following dose regimen has been shown to have great effect:10 mg/kg/h from the start of surgery until 2 hours after reperfusion of the liver transplant. Although TXA is not currently approved for use in patients undergoing major liver resection, Health Canada has allowed the use of tranexamic acid for use in this research study.

Official Title
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Open Label, Non-Randomized, Study to Evaluate the Pharmacokinetics of Tranexamic Acid in Patients Undergoing Major Liver Resection

Conditions
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Cancer, Tumour, Surgery

Intervention / Treatment
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* Drug: No tranexamic acid
* Drug: Tranexamic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patient undergoing anticipated open or laparoscopic major liver resection (> 2 hepatic segments), as assessed by the operating surgeon Age ≥ 18 years. Exclusion Criteria Previously enrolled in this study Platelet count less than 100,000/mm3 Severe anemia (hemoglobin levels less than 90 g/l) Documented arterial or venous thrombosis at screening or in past three months Anticoagulants (other than LMWH or heparin in prophylactic doses to prevent deep vein thrombosis), direct thrombin inhibitors or thrombolytic therapy administered or completed within last week Hepatectomy associated with planned vascular or biliary reconstruction Known disseminated intravascular coagulation Severe renal insufficiency (CrCl<30) History of seizure disorder Pregnant or lactating Hypersensitivity to tranexamic acid or any of the ingredients Unable to receive blood products (i.e. difficulty with cross matching, refuses blood transfusion, or a past history of unexplained severe transfusion reaction) Receipt of chemotherapy within 4 weeks of scheduled operation Patients undergoing resection for living donor liver transplant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard Care<br>No tranexamic acid | Drug: No tranexamic acid<br>* Control<br>|
| Experimental: Dose 1<br>1 g bolus + 1 g infusion from induction over 8 hours | Drug: Tranexamic Acid<br> <br> * Other names: Cyklokapron;|
| Experimental: Dose 2<br>1 g bolus + 10 mg/kg/hr from induction until end of surgery | Drug: Tranexamic Acid<br> <br> * Other names: Cyklokapron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Receipt of blood transfusion(s) |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibrinolytic Markers |  | Baseline - Postoperative Day 0-7 | 
| Pharmacokinetic Study |  | Baseline - Postoperative Day 0-7 | 
| Post-operative incidence of symptomatic venous thromboembolic event |  | 30 days | 
| Other post-operative complications |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood transfusion, Blood loss, Postoperative complications, Outcome