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

Phase 4

Recruiting

• Conditions: Antifibrinolytic Agents
• Interventions: Drug: Tranexamic acid bolus 10 mg/kg; Drug: Tranexamic acid bolus 20 mg/kg; Drug: Tranexamic acid bolus 1 mg/kg; Drug: Tranexamic acid continuous infusion of 1 mg/kg/h in the low dose group

• Registration Number: NCT06128330
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-07
• Study First Submitted QC: 2023-11-07
• Study First Posted: 2023-11-13
• Study Start: 2023-12-15
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-07
• Last Update Posted: 2024-03-08
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 322

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low dose group	Tranexamic acid continuous infusion of 1 mg/kg/h in the low dose group	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.
Low dose group	Tranexamic acid bolus 10 mg/kg	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.
Standard dose group	Tranexamic acid bolus 20 mg/kg	The standard dose group will receive a bolus of 20 mg/kg tranexamic acid after anaesthesia induction.
Low dose group	Tranexamic acid bolus 1 mg/kg	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.

Primary Outcome Measures

Name	Time	Method
TPA test	48 hours after completion of surgery	The primary endpoint of the study is if the antifibrinolytic activity as measured with the TPA assay. The result can be positive (no fibrinolysis and good antifibrinolytic activity) or negative (fibrinolysis and no antifibrinolytic activity).The TPA assay is performed at five different time points until the 2. postoperative day (48 hours).

Secondary Outcome Measures

Name	Time	Method
Chromatography	48 hours after completion of surgery	Secondary endpoint is the TXA concentration as measured by chromatography.

Trial Locations

Locations (1)

Dpt. Anesthesiology and pain Medicine; 🇨🇭 Berne, Switzerland