Comparison of Topical and Infusion Tranexamic Acid After Total Knee Arthroplasty

Study Overview
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Brief Summary
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The purpose of the study, therefore, is to conduct a prospective randomized controlled trial to investigate the blood-conservation effect of TXA in different TKA patients groups with rivaroxaban for VTE prophylaxis, first group by topical application, second group by infusion and a third group of placebo and observe whether there is difference in the occurrence of venous thromboembolism in those patient groups by venographic study

Detailed Description
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Investigators 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%. However, most of the orthopedic surgeons still hesitate to use TXA systemically in TKAs especially in high risk patients with a potential increase in thromboembolic events following surgery. Because of this concern, recently, there were few reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients. However, most of the reports compared the topical TXA with placebo in TKA patients, not with intravenous TXA. Recently, Georgiadis et al. conducted a double-blind, randomized controlled clinical trial are demonstrated similar transfusion rate and perioperative blood loss between topical administration and intravenous injection of TXA in TKA patients. There were no significant safety differences between the two groups. Low-molecular weight heparin (LMWH) was used for thromboembolism prophylaxis in that study. Recently, chemical VTE prophylaxis such as rivaroxaban has been approved as a standard care after TKA because of its superior convenience and efficacy on VTE prophylaxis to LMWH in TKAs. However, because of direct blockage of the formation of thrombin from prothrombin by rivaroxaban, an increased postoperative bleeding has been reported. There have been little studies investigating the blood-conservation effect of TXA on TKA patients either by infusion or by topical application when rivaroxaban used as VTE prophylaxis.

Official Title
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Comparison of Topical and Infusion Tranexamic Acid on Blood Loss and Risk of Deep Vein Thrombosis After Total Knee Arthroplasty

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Tranexamic Acid 5%,5ml/amp
* Drug: Tranexamic Acid 5%,5ml/amp
* Drug: rivaroxaban (10mg)
* Drug: 0.9% Normal Saline
* Drug: 0.9% Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: End-stage arthritis of the knee Failure of medical treatment or rehabilitation Hemoglobin > 10g/dl No use of non-steroid anti-inflammatory agent one week before operation Exclusion Criteria: Preoperative Hemoglobin ≦10 g/dl History of infection or intraarticular fracture of the affective knee Renal function deficiency (GFR < 55 ml/min/1.73m2)which is relative contraindicated for venography Elevated liver enzyme, history of liver cirrhosis, impaired liver function and coagulopathy (including long-term use anticoagulant) History of deep vein thrombosis, ischemic heart disease or stroke

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Topic TXA group<br>Primary total knee replacement with intravenous 0.9% normal saline (20 ml) administration before deflation of the tourniquet and intraarticular application of Tranexamic Acid 5%,5ml/amp 3g (60ml) in 100 ml normal saline into knee joint after closure of the joint capsule Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis | Drug: Tranexamic Acid 5%,5ml/amp<br>* Intraarticular application of tranexamic acid 3g (60ml) in 100 ml normal saline into knee joint after closure of the joint capsule<br>* Other names: Transamine;Drug: rivaroxaban (10mg)<br>* Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14.<br>* Other names: Xarelto;Drug: 0.9% Normal Saline<br>* Primary total knee replacement with intravenous normal saline (20 ml) administration before deflation of the tourniquet<br>* Other names: 0.9% sodium chloride;|
| Active Comparator: IV TXA group<br>Primary total knee replacement with 1 g Tranexamic Acid 5%,5ml/amp administrated intravenously before deflection of the tourniquet and topical 160 ml 0.9% normal saline application after closure of joint capsule. Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis | Drug: Tranexamic Acid 5%,5ml/amp<br>* IV TXA group: Primary total knee replacement with 1 g tranexamic acid administrated intravenously before deflection of the tourniquet<br>* Other names: Transamine;Drug: rivaroxaban (10mg)<br>* Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14.<br>* Other names: Xarelto;Drug: 0.9% Normal Saline<br>* Topical 160 ml normal saline application after closure of joint capsule.<br>* Other names: 0.9% sodium chloride;|
| Placebo Comparator: Control group<br>Primary total knee replacement with 0.9% normal saline administration intravenously before deflation of the tourniquet and topical 160 ml 0.9% normal saline application after closure of joint capsule. Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis | Drug: rivaroxaban (10mg)<br>* Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14.<br>* Other names: Xarelto;Drug: 0.9% Normal Saline<br>* Primary total knee replacement with intravenous normal saline (20 ml) administration before deflation of the tourniquet<br>* Other names: 0.9% sodium chloride;Drug: 0.9% Normal Saline<br>* Topical 160 ml normal saline application after closure of joint capsule.<br>* Other names: 0.9% sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality | Primary efficacy outcome is the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality | within 15 days after surgery (2 days after the last dose of rivaroxaban ) | 
| Incidence of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings | Primary safety outcome is the composite of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings Major bleeding was defined as bleeding that was fatal, that involved a critical organ, or that required reoperation or clinically overt bleeding outside the surgical site that was associated with a decrease in the hemoglobin level of 2 g or more per deciliter or requiring infusion of 2 or more units of blood | within 15 days after surgery (2 days after the last dose of rivaroxaban ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of major venous thromboembolism | the secondary efficacy outcomes include major venous thromboemolism defined as the composite of proximal deep-vein thrombosis, non-fatal pulmonary embolism, and VTE related death | within 15 days after surgery (2 days after the last dose of rivaroxaban ) | 
| Secondary safety outcome was composite of any non-major bleeding and all wound complications after operation | non-major bleeding including hemorrhagic wound complications (excessive wound hematoma or bleeding at the surgical site | within 15 days after surgery (2 days after the last dose of rivaroxaban ) | 
| Incidence of wound complications after surgery | composite of hematoma, superficial wound infection, and deep infection requiring return to surgery | within 30 days of the procedure | 
| Total blood loss after surgery | 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 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tranexamic Acid, Total Knee Arthroplasty, Rivaroxaban