Antifibrinolytic Agents
Conditions
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.
Interventions
DRUGTranexamic acid bolus 20 mg/kg
Bolus of tranexamic acid in the standard dose group
DRUGTranexamic acid bolus 10 mg/kg
Bolus of tranexamic acid in the low dose group
DRUGTranexamic acid bolus 1 mg/kg
Bolus of tranexamic acid in the low dose group (to add into the CPB prime)
DRUGTranexamic acid continuous infusion of 1 mg/kg/h in the low dose group
Tranexamic acid continuous infusion during the procedure
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Chromatography | 48 hours after completion of surgery | Secondary endpoint is the TXA concentration as measured by chromatography. |
Countries
Switzerland
Contacts
Primary ContactGabor Erdoes, MD
Outcome results
None listed