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

Antifibrinolytic Agents Clinical Trial

— PAATICS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06128330
• Other study ID #: 2022-02070
• Status: Recruiting
• Phase: Phase 4
• Start date: December 15, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Gabor Erdoes, MD
• Phone: ++41 31 632 2726
• Email: Gabor.erdoes[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 322
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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)

Related Conditions & MeSH terms

• Antifibrinolytic Agents

Intervention

Drug:
• Tranexamic acid bolus 20 mg/kg
Bolus of tranexamic acid in the standard dose group
• Tranexamic acid bolus 10 mg/kg
Bolus of tranexamic acid in the low dose group
• Tranexamic acid bolus 1 mg/kg
Bolus of tranexamic acid in the low dose group (to add into the CPB prime)
• Tranexamic acid continuous infusion of 1 mg/kg/h in the low dose group
Tranexamic acid continuous infusion during the procedure

Locations

Country	Name	City	State
Switzerland	Dpt. Anesthesiology and pain Medicine	Berne

Sponsors (1)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Chromatography	Secondary endpoint is the TXA concentration as measured by chromatography.	48 hours after completion of surgery