Tranexamic Acid in Clopidogrel Exposure to Decrease Hemorrhage and Transfusion

Study Overview
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Brief Summary
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The use of platelet aggregation inhibitors, including aspirin and clopidogrel(CPDG), has become a standard management strategy for patients with acute coronary syndrome. On this background, an increasing percentage of patients presenting for surgical coronary revascularization is the subject to irreversible platelet inhibition. Investigations on the effect of antiplatelet treatment on postoperative bleeding after cardiac surgery have shown that patients treated with antiplatelet agents until surgery have increased postoperative bleeding, and also an increased need for transfusions of blood products. As a result of the antiplatelet effect of clopidogrel, the frequency of serious bleeding complications has increased significantly, as seen in patients requiring coronary artery bypass grafting(CABG), especially when they received clopidogrel until surgery. Tranexamic acid(TA) is a widely used antifibrinolytic agent, and is a promising substitute for aprotinin when the latter has seceded in 2007.The release of plasmin during cardiopulmonary bypass(CPB) activates fibrinolysis and may contribute to platelet dysfunction. Pharmacological inhibition of the fibrinolytic system may therefore ameliorate platelet dysfunction and fibrinolysis after CPB and decrease postoperative bleeding. Tranexamic acid prevents plasmin formation and inhibits fibrinolysis. Concerning the cessation of aprotinin and the increasing proportion of patients with persistence on clopidogrel until their surgery, evolutional work is expected, especially in the eastern population. The purpose of this study is to assess the effect of tranexamic acid in patients with clopidogrel and asprin ingestion until surgery. The investigators working hypothesis was that tranexamic acid would lower postoperative blood loss and transfusion requirements in these patients and would attenuate bleeding complication of antiplatelet therapy.

Official Title
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Effects of Antifibrinolytics on Bleeding and Transfusion Outcomes in Patients Receiving Coronary Artery Bypass Surgery With Preoperative Clopidogrel Exposure

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients requiring primary and isolated coronary artery bypass grafting with cardiopulmonary bypass Exclusion Criteria: history of cardiac surgery hematocrit <33% platelet count <100,000/ml allergy to tranexamic acid recruited in other studies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group ET<br>Patients receiving early CABG <=7 days of the cessation of clopidogrel, treated with tranexamic acid with a bolus of 10 mg/kg after anesthetic induction and a maintenance of 10 mg/kg/h for the duration of surgery. | Drug: Tranexamic Acid<br>* A bolus of 10 mg/kg after anesthetic induction over 10 min followed by a maintenance of 10 mg/kg/h for the duration of surgery<br>|
| Placebo Comparator: group EP<br>Patients receiving early CABG <= 7 days of the cessation of clopidogrel, treated with placebo(saline solution) | Drug: Saline<br>* Saline served as placebo<br>|
| Experimental: group LT<br>Patients receiving late CABG >7 days of the cessation of clopidogrel, treated with tranexamic acid with a bolus of 10 mg/kg after anesthetic induction and a maintenance of 10 mg/kg/h for the duration of surgery. | Drug: Tranexamic Acid<br>* A bolus of 10 mg/kg after anesthetic induction over 10 min followed by a maintenance of 10 mg/kg/h for the duration of surgery<br>|
| Placebo Comparator: group LP<br>Patients receiving late CABG >7 days of the cessation of clopidogrel, treated with placebo(saline solution) | Drug: Saline<br>* Saline served as placebo<br>|
| Experimental: group BT<br>Patients receiving CABG without preoperative clopidogrel exposure, treated with tranexamic acid with a bolus of 10 mg/kg after anesthetic induction and a maintenance of 10 mg/kg/h for the duration of surgery. | Drug: Tranexamic Acid<br>* A bolus of 10 mg/kg after anesthetic induction over 10 min followed by a maintenance of 10 mg/kg/h for the duration of surgery<br>|
| Placebo Comparator: group BP<br>Patients receiving CABG without preoperative clopidogrel exposure, treated with placebo(saline solution) | Drug: Saline<br>* Saline served as placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative blood loss(chest drainage) |  | on the 120th day postoperatively | 
| Incidence of major bleeding |  | on the 120th day postoperatively | 
| RBC Transfusion (volume and rate) |  | on the 120th day postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | on the 120th day postoperatively | 
| Major morbidity | The major morbidity end points were defined as permanent disability caused by stroke, postoperative myocardial infarction, renal failure and respiratory failure. | on the 120th day postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clopidogrel, Tranexamic Acid, Cardiac Surgical Procedures, Hemostasis