Clinical trial NCT01651182: Tranexamic Acid Versus Placebo for Blood to Reduce Perioperative Bleeding Post-liver Resection
Official title: Open Label, Non-Randomized, Study to Evaluate the Pharmacokinetics of Tranexamic Acid in Patients Undergoing Major Liver Resection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cancer
Tumour
Surgery
Keywords: Blood transfusion
Blood loss
Postoperative complications
Outcome
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: University of Toronto
name: University Health Network, Toronto
First posted: 2012-07-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Receipt of blood transfusion(s)
timeFrame: 7 days
Secondary outcomes:
measure: Fibrinolytic Markers
timeFrame: Baseline - Postoperative Day 0-7
measure: Pharmacokinetic Study
timeFrame: Baseline - Postoperative Day 0-7
measure: Post-operative incidence of symptomatic venous thromboembolic event
timeFrame: 30 days
measure: Other post-operative complications
timeFrame: 30 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Paul Karanicolas, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karanicolas PJ, Lin Y, Tarshis J, Law CH, Coburn NG, Hallet J, Nascimento B, Pawliszyn J, McCluskey SA. Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid. HPB (Oxford). 2016 Dec;18(12):991-999. doi: 10.1016/j.hpb.2016.09.005. Epub 2016 Oct 18.