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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 322
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gabor Erdoes, MD; Phone Number: ++41 31 632 2726; Email: Gabor.erdoes@insel.ch

Study Locations

• Switzerland
  • Berne, Switzerland, 3010
    • Recruiting
    • Dpt. Anesthesiology and pain Medicine
    • Contact: Gabor Erdoes, MD; Phone Number: +41316322726; Email: gabor.erdoes@insel.ch
    • Contact: Annegret Kauert-Willms, MD; Phone Number: +41316322111; Email: annegret.kauert@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard dose group; The standard dose group will receive a bolus of 20 mg/kg tranexamic acid after anaesthesia induction.	Drug: Tranexamic acid bolus 20 mg/kg; Bolus of tranexamic acid in the standard dose group
Experimental: 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.	Drug: Tranexamic acid bolus 10 mg/kg; Bolus of tranexamic acid in the low dose group; Drug: Tranexamic acid bolus 1 mg/kg; Bolus of tranexamic acid in the low dose group (to add into the CPB prime); Drug: Tranexamic acid continuous infusion of 1 mg/kg/h in the low dose group; Tranexamic acid continuous infusion during the procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TPA test	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).	48 hours after completion of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chromatography	Secondary endpoint is the TXA concentration as measured by chromatography.	48 hours after completion of surgery

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Annegret Kauert-Willms, MD, University Hospital Berne

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antifibrinolytic Agents; Fibrin Modulating Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 2022-02070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No