Combined Topical Tranexamic Acid With Floseal® in Total Knee Arthroplasty

Study Overview
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Brief Summary
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Our purpose of this study therefore is to conduct a prospective randomized controlled trial to investigate the blood-conservation effect of combined topical application of these two hemostatic agents in different time during surgery and the safety compared with single topical application of TKA in a primary TKA procedure

Detailed Description
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Total knee arthroplasty (TKA) is associated with considerable blood loss and increasing needs for allogenic blood transfusion. Tranexamic acid (TXA), an inhibitor of fibrinolysis, was reportedly effective reducing blood loss after standard TKA. Our previous experiences in minimally invasive (MIS) TKA showed that intraoperative infusion of TXA reduced 45% of postoperative blood loss and needs for transfusion from 20% to 4%. There were some reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients. Besides, thrombin-based hemostatic agents, Floseal®(Baxter, Deerfield, Illinois), have been widely used in surgical procedure. Some recent studies demonstrated that topical use of Floseal® in primary TKA can reduce hemoglobin decline and calculated total blood loss after TKA. But other studies showed Floseal® does not reduce blood loss in TKA procedures. We believe the topical use of hemostatic agent in patients with high risk of thromboembolism can avoid its systematic effect and decrease its potential perioperative risk of thromboembolic complications (arterial thrombosis, myocardial infarction and pulmonary embolism). Recently, there were some reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients. The blood saving effect of topical application of TXA in primary TKA was similar with systemic administration. The mean total blood loss of topical route of TXA inTKA patients was 940-1295 ml in different reports which was still high for patients with high thromboembolic risks. However, the efficacy and safety of topical use of TXA in TKA patients with history of thromboembolic disease is still unclear. A more effective regimen for bleeding prophylaxis afer primary TKA is necessary. We believe that combined topical applications of two hemostatic agents of different mechanisms can bring a synergistic effect in blood saving and does not increase the risk of thromboembolic disease after TKA. Our purpose of this study therefore is to conduct a prospective randomized controlled trial to investigate the blood-conservation effect of combined topical application of these two hemostatic agents in different time during surgery and the safety compared with single topical application of TKA in a primary TKA procedure.

Official Title
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Comparison of Combined Topical Tranexamic Acid With Floseal® With Intravenous Tranexamic Acid on Blood Loss in Total Knee Arthroplasty

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Topical tranexamic acid
* Drug: Floseal®
* Drug: rivaroxaban (10mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have advanced knee osteoarthritis are scheduled to undergo primary, unilateral elective total knee replacement surgery Age > 50 years and < 90 years Failure of medical treatment or rehabilitation. Hemoglobin > 11g/dl, No use of non-steroid anti-inflammatory agent one week before operation Exclusion Criteria: Preoperative Hemoglobin ≦11 g/dl History of infection or intraarticular fracture of the affective knee Renal function deficiency (GFR <30 ml/min/1.73m2)which is relative contraindicated for chemical venous thromboembolism Elevated liver enzyme (AST/ALT level are more than twice normal range) , history of liver cirrhosis, impaired liver function(elevated total bilirubin level) and coagulopathy (including long-term use anticoagulant) History of deep vein thrombosis, ischemic heart disease or stroke Contraindications of tranexamic acid, floseal, or rivaroxaban Allergy to tranexamic acid, floseal, rivaroxaban, or the excipients History of heparin-induced thrombocytopenia (HIT) Coagulopathy or bleeding tendency caused by organ dysfunction, such as cirrhosis, bone marrow suppression etc. Patient who have active bleeding disorder, such as intracranial hemorrhage, upper GI bleeding, hematuria. Patients with known allergies to materials of bovine origin

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Combined topical TXA and Floseal<br>Floseal® was applied on potential bleeding sites before prosthesis implantation, and intraarticular application of topical tranexamic acid after capsule closure Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14. | Drug: Topical tranexamic acid<br>* Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule<br>* Other names: Topical transamine;Drug: Floseal®<br>* Floseal® (Hemostatic matrix, 10ml, Baxter) was applied on potential bleeding sites: the femoral insertion of the posterior cruciate ligament, the lateral genicular artery after resection of the meniscus, the posterior capsule of the knee joint, the bony surfaces not covered by the implant as well as the pinholes (femur and tibia). The entire content of a 10 mL vial containing the active product (Floseal®) was used. The HM remained in place for 3 minutes and was then gently rinsed from the knee as recommended by the manufacturer (Baxter)<br>* Other names: Thrombin-gelatin matrix;Drug: rivaroxaban (10mg)<br>* Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.<br>* Other names: Xarelto;|
| Active Comparator: Topical TXA alone<br>Intraarticular application of topical tranexamic acid after capsule closure Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14. | Drug: Topical tranexamic acid<br>* Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule<br>* Other names: Topical transamine;Drug: rivaroxaban (10mg)<br>* Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.<br>* Other names: Xarelto;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Blood Loss After Operation | Total blood loss was calculated according to Nadler et al., which used maximum postoperative reduction of the Hb level adjust for weight and height of the patient. The formula is as follows, Total blood loss = (Total blood volume x [change in Hb level / preoperative Hb level])x1000+volume transfused | From the operation to the postoperative day 3 or 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Transfusion Rate | We will record the event of blood transfusion, and calculate the incidence of transfusion | From the operation to the postoperative day 3 or 4 | 
| Incidence of Thrombosis Events | The composite of any venous thromoembolism events, ischemic heart attacks, cerebrovascular accidents | within 30 days of the operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombin-gelatin matrix, Floseal, Tranexamic Acid, Total Knee Arthroplasty