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

Sunnybrook Health Sciences Centre

Status and phase: Completed; Phase 3

Conditions: Surgery; Cancer; Tumour

Treatments: Drug: Tranexamic Acid; Drug: No tranexamic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT01651182

TXA Liver - PK

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

24 participants in 3 patient groups, including a placebo group

Standard Care

Placebo Comparator group

Description:

No tranexamic acid

Treatment:

Drug: No tranexamic acid

Dose 1

Experimental group

Description:

1 g bolus + 1 g infusion from induction over 8 hours

Treatment:

Drug: Tranexamic Acid

Dose 2

Experimental group

Description:

1 g bolus + 10 mg/kg/hr from induction until end of surgery

Treatment:

Drug: Tranexamic Acid