Point-of-care Measurement of the Antifibrinolytic Activity of Tranexamic Acid in Cardiac Surgery (PAATICS)

Insel Gruppe AG, University Hospital Bern

Status and phase: Enrolling; Phase 4

Conditions: Antifibrinolytic Agents

Treatments: Drug: Tranexamic acid bolus 10 mg/kg; Drug: Tranexamic acid continuous infusion of 1 mg/kg/h in the low dose group; Drug: Tranexamic acid bolus 1 mg/kg; Drug: Tranexamic acid bolus 20 mg/kg

Study type: Interventional

Funder types: Other

Identifiers

NCT06128330

2022-02070

Details and patient eligibility

About

Tranexamic acid (TXA) is a widely used antifibrinolytic agent that can reduce postoperative blood loss and packed red blood cell transfusions during cardiac surgery. Previous (in-vivo) studies have measured TXA plasma concentration and associated clinical effect (e.g. blood loss). Patient blood management guidelines recommend the routine use of TXA in cardiac surgery, especially for procedures with a high risk of bleeding.

A new point-of-care viscoelastic diagnostic assay (tissue plasminogen activator assay, TPA assay) allows for a rapid determination of antifibrinolytic activity in a patient in the operating room making TXA dose adjustment easily possible intraoperatively. Currently, there is no consensus on the dosing of TXA and different protocols are used. Recommendations for high doses (e.g. 30 mg/kg followed by 16 mg/kg per hour during cardiac surgery with 2 mg/kg added to extracorporeal circulation) alternate with recommendations for low doses (e.g., 10 mg/kg followed by 1 mg/kg per hour for 12 hours).

Tranexamic acid administration increases the risk of postoperative seizure, a risk that appears to be dose dependant. A recent meta-analysis suggests that a single TXA bolus of 20 mg/kg is sufficient to reduce postoperative blood loss and packed red blood cell transfusion in patients undergoing aortocoronary bypass surgery. The calculations in the meta-analysis were, however, based on a simulation of blood concentrations of TXA by a pharmacokinetic model, so the results are subject to many uncertainties. The optimal TXA regimen for cardiac surgery, both in terms of efficacy and safety therefore remains uncertain and requires further investigation.

This study was invented to determine the actual levels of tranexamic acid in vivo to observe antifibrinolytic activity during cardiac surgery up to 48 hours after termination of surgery. The risk category is evaluated as risk category A as the study is a clinical trial examining the effect of drugs that are already authorized for the clinical use.

Enrollment: 322 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Eligible patients:

• Over 18 years old
• Elective surgery
• Written informed consent
• Patient planned for aortocoronary artery bypass graft surgery, aortic valve replacement or mitral valve surgery (or a combination of these procedures)
• Normal renal function
• No previous intake of anticoagulants except acetylsalicylic acid in the preoperative period

Exclusion criteria

• Impaired renal function (eGFR < 30 ml/min.)
• History of seizure
• Pregnancy
• Inability to understand and sign the informed consent (e.g., language problems, dementia, psychological disorders)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

322 participants in 2 patient groups

Standard dose group

Active Comparator group

Description:

The standard dose group will receive a bolus of 20 mg/kg tranexamic acid after anaesthesia induction.

Treatment:

Drug: Tranexamic acid bolus 20 mg/kg

Low dose group

Experimental group

Description:

The low dose group will receive a bolus of 10 mg/kg tranexamic acid. In addition 1 mg/kg tranexamic acid will be added to the priming of the extracorporeal circuit (ECC) and a continuous infusion of 1mg/kg/h tranexamic acid will be started after the bolus infusion until the end of surgery.

Treatment:

Drug: Tranexamic acid continuous infusion of 1 mg/kg/h in the low dose group

Drug: Tranexamic acid bolus 1 mg/kg

Drug: Tranexamic acid bolus 10 mg/kg