Tranexamic Acid, Hemorrhage and Transfusions After Combined Aortic Valve Replacement and Coronary Artery Bypass Surgery.

Study Overview
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Brief Summary
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In this study we will investigate whether tranexamic acid given as an intravenous bolus injection before start of surgery, followed by a continuous infusion during surgery reduces, perioperative hemostatic activation, and postoperative bleeding and the need for transfusions of blood components in elderly patients undergoing combined aortic valve replacement and coronary artery bypass surgery. Tranexamic acid will be compared with placebo (0.9% sodium chloride) in a randomized and double-blind study design. The study hypothesis is that tranexamic acid will reduce hemostatic activation and postoperative hemorrhage and the need for blood component transfusions in this group of patients.

Detailed Description
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It has previously been shown that elderly patients show signs of increased perioperative hemostatic activation after coronary artery bypass grafting. In particular, compared to younger patients, elderly patients had more extensive fibrinolysis postoperatively. The antifibrinolytic drug tranexamic acid has been shown to reduce fibrinolysis, bleeding, and the need for transfusions of blood components after various cardiac surgical procedures. In this study we will investigate whether tranexamic acid reduces perioperative activation of coagulation as measured by plasma concentrations of antithrombin, thrombin-antithrombin complex, and prothrombin fragment 1+2, whether tranexamic acid reduces perioperative fibrinolysis as measured by plasma concentrations of D-dimer, and whether tranexamic acid reduces platelet activation as measured by plasma concentrations of neutrophil activating peptide 2 and by flow cytometry in elderly (above 70 years of age) patients undergoing combined aortic valve replacement and coronary artery bypass surgery. The primary endpoint of the study will, however, be total postoperative bleeding and the need for transfusions of blood components during and after surgery. The need for transfusions will be registered during the whole hospital stay. Patients will be randomized into two groups and given either tranexamic acid or placebo (0.9% sodium chloride) as an intravenous bolus injection before start of surgery followed by an intravenous infusion during surgery. Blood samples for the above mentioned plasma concentration measurements will be drawn preoperatively, intraoperatively during CPB, and 30 minutes and 3, 5, and 20 hours postoperatively. Postoperative bleeding will be registered for 16 hours. The need for any transfusions of blood products will be registered for the whole hospital stay.

Official Title
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Phase 4 Study of Tranexamic Acid for Elderly Patients Undergoing Combined Aortic Valve Replacement and Coronary Artery Bypass Surgery.

Conditions
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Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic acid
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients above 70 years of age scheduled for combined aortic valve replacement and coronary artery bypass surgery. - Exclusion Criteria: Patients younger than 70 years of age. Patients scheduled for other procedures than combined aortic valve replacement and coronary artery bypass surgery. Patients who are not treated with aspirin. Patients with a medical condition known to influence the hemostatic system. Patients treated with drugs other than aspirin during the last week before surgery that may influence the hemostatic system, such as warfarin (coumarin), non-steroidal antiinflammatory drugs, clopidogrel, heparin, low molecular heparins. Patients who are treated with systemic steroids. Patients with a serum creatinin concentration above 140 micromol/l. Patients with an INR above 1.5. Patients who are not able to give written informed concent. -

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic Acid<br> | Drug: Tranexamic acid<br>* Tranexamic acid 10 mg/kg as a bolus dose followed by an infusion of 1 mg/kg/hour. Bolus given before start of surgery, infusion continued during surgery.<br>* Other names: Cykokapron ACT: B02A A02;|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* 0.9% sodium chloride 10 mg/kg, as a bolus injection before surgery followed by 1 mg/kg/h as an infusion during surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfusion of blood components |  | Intraoperatively and during postoperative stay | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative hemorrhage |  | First 16 hours postoperatively | 
| Fibrinolysis |  | 20 hours postoperatively | 
| Platelet activation |  | 20 hours postoperatively | 
| Activation of coagulation |  | 20 hours postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemorrhage, Transfusion, Blood components, Fibrinolysis, Platelet activation