Point-of-care Measurement of the Antifibrinolytic Activity of Tranexamic Acid in Cardiac Surgery
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 322
- 试验地点
- 1
- 主要终点
- TPA test
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Standard dose group
The standard dose group will receive a bolus of 20 mg/kg tranexamic acid after anaesthesia induction.
干预措施: Tranexamic acid bolus 20 mg/kg (Drug)
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.
干预措施: Tranexamic acid bolus 10 mg/kg (Drug)
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.
干预措施: Tranexamic acid bolus 1 mg/kg (Drug)
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.
干预措施: Tranexamic acid continuous infusion of 1 mg/kg/h in the low dose group (Drug)
结局指标
主要结局
TPA test
时间窗: 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).
次要结局
- Chromatography(48 hours after completion of surgery)