Topical Effect of Tranexamic Acid in Postoperative Bleeding and Blood Products Transfusion After Cardiac Surgery

Study Overview
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Brief Summary
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This is a single-center, double-blind, randomized controlled trial (RCT) comparing two groups of application of topical dose of tranexamic acid (TxA) versus placebo in patients undergoing coronary artery bypass graft (CABG), off pump coronary bypass graft cardiac surgery (OPCAB), and adult heart valve surgery. The primary outcomes of this study comprised of two parameters; post operative bleeding and blood product transfusion. The primary outcomes were assessed during the operation, until 48-hour post operative.

Detailed Description
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A single center randomized controlled trial (RCT) was conducted at Harapan Kita National Cardiovascular Center, Jakarta, Indonesia as the tertiary cardiovascular referral hospital. The RCT was conducted from October 1 th, 2022 until January 6 th, 2023 (current status: completed). This study aims to determine whether topical tranexamic acid is more effective on the amount of bleeding and the need for postoperative blood product transfusion compared with placebo in patients undergoing cardiac surgery and specifically measure the difference outcome between coronary artery bypass graft (CABG), off pump coronary bypass graft cardiac surgery (OPCAB), and adult heart valve surgery. The control group in this study is given 100 mL of normal saline. The subjects were adults undergoing elective cardiac surgery (CABG, OPCAB, and heart valve surgery). Both the patients and the principal investigators were blinded for the treatment-control allocation. The patients were purposively selected and were randomly assigned to one of the arms with block randomization. The primary outcomes of this study comprised of two parameters; post operative bleeding and blood product transfusion. The primary outcomes were assessed during the operation, until 48-hour post operative.

Official Title
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Topical Application Effect of Tranexamic Acid in Postoperative Bleeding and Blood Products Transfusion After Cardiac Surgery

Conditions
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Coronary Artery Disease, Valvular Heart Disease, Surgical Blood Loss

Intervention / Treatment
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* Drug: Tranexamic Acid 100 MG/ML
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ages > 18 years old Patients who are scheduled electively for cardiac surgery in National Heart Center Harapan Kita, Jakarta, Indonesia Patients with heart valve disease indicated for aortic or mitral repair/replace Patients with coronary artery disease indicated for CABG or OPCAB surgery Aortic and/ mitral valve surgery concomitant with tricuspid repair Patients who are agreed to participate in this study Exclusion Criteria: Not willing to become research subjects Allergy to tranexamic acid Undergoing minimally invasive surgery Undergoing double valve (aorta & mitral) procedure and double procedure (CABG+valve, valve+maze) Emergency surgery History of bleeding disorder or coagulopathy History of thromboembolic or hemorrhagic disease Active Infective endocarditis History of previous cardiac surgery Estimated glomerular filtration rate <30 mL/min or on dialysis Receiving oral therapy with clopidogrel, aspirin, dabigatran, or rivaroxaban in the last five days Receiving chronic warfarin therapy who have not stopped their medication and have an international normalized ratio (INR) >1.5 before surgery Pre-operative thrombocytopenia (<50,000 platelets per µL) Pregnancy or breast feeding Refusal of blood products Pericarditis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: A double-blind, single center, parallel phase 4 randomized clinical trial was conducted with two intervention arms: an intervention arm with the use of tranexamic acid topical and a control arm with the use of normal saline in which the subjects' recruitment and treatment were conducted simultaneously by means of a block randomization.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic Acid Topical<br>The treatment of interest was application of Topical Tranexamic Acid (5 gram in 50 mL warm normal saline). The topical will be poured into the pericardial and mediastinal cavities (after protamine administration), and sternum (before chest closure) | Drug: Tranexamic Acid 100 MG/ML<br>* Tranexamic acid is a synthetic derivative of lysine used as an antifibrinolytic in the treatment and prevention of major bleeding. Tranexamic acid competitively and reversibly inhibits the activation of plasminogen via binding at several distinct sites, including four or five low-affinity sites and one high-affinity site, the latter of which is involved in its binding to fibrin. The binding of plasminogen to fibrin induces fibrinolysis - by occupying the necessary binding sites tranexamic acid prevents this dissolution of fibrin, thereby stabilizing the clot and preventing hemorrhage<br>* Other names: Tranexamic Acid;|
| Placebo Comparator: Placebo<br>The control group is given 100 mL of warm normal saline. The topical will be poured into the pericardial and mediastinal cavities (after protamine administration), and sternum (before chest closure). | Drug: normal saline<br>* Normal saline is a cornerstone of intravenous solutions commonly used in the clinical setting. It is a crystalloid fluid administered via an intravenous solution. Its indications include both adult and pediatric populations as sources of hydration and electrolyte disturbances<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial Postoperative bleeding | The study parameter is assessed by postoperative chest tube production immediately after the surgery | immediately after the surgery | 
| 6-hour postoperative bleeding | The study parameter is asses the accumulation of drain production within 6 hours postoperatively after surgical procedure | within 6-hour after the surgery | 
| 24-hour postoperative bleeding | The study parameter is asses the accumulation of drain production within 24 hours postoperatively after surgical procedure | within 24-hour after the surgery | 
| 48-hour postoperative bleeding | The study parameter is asses the accumulation of drain production within 48 hours postoperatively after surgical procedure | within 48-hour after the surgery | 
| Postoperative blood product transfusion | The amount of red blood cell, fresh frozen plasma, thrombocyte concentrate, and cryoprecipitate transfusions the patient receive postoperatively during their stay in the hospital. | participants will be followed for the duration of ICU and intermediate ward stay, an expected average of 5-7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OPCAB, Heart Valve Surgery, Tranexamic Acid, Postoperative Bleeding, Blood Product Transfusion, CABG