Combined Topical Tranexamic Acid With Floseal® in Total Knee Arthroplasty

Phase 4

Completed

• Conditions: Osteoarthritis, Knee
• Interventions: Drug: Topical tranexamic acid; Drug: Floseal®; Drug: rivaroxaban (10mg)

• Registration Number: NCT03328832
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-09-12
• Study First Submitted: 2017-10-30
• Study First Submitted QC: 2017-10-30
• Study First Posted: 2017-11-01
• Primary Completion: 2018-09-30
• Study Completion: 2018-12-30
• Status Verified: 2021-07
• Results First Submitted: 2021-07-19
• Results First Submitted QC: 2021-07-19
• Last Update Submitted: 2021-07-19
• Results First Posted: 2021-08-10
• Last Update Posted: 2021-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Patients who have advanced knee osteoarthritis are scheduled to undergo primary, unilateral elective total knee replacement surgery
2. Age > 50 years and < 90 years
3. Failure of medical treatment or rehabilitation.
4. Hemoglobin > 11g/dl,
5. No use of non-steroid anti-inflammatory agent one week before operation

Exclusion Criteria

1. Preoperative Hemoglobin ≦11 g/dl
2. History of infection or intraarticular fracture of the affective knee
3. Renal function deficiency (GFR <30 ml/min/1.73m2)which is relative contraindicated for chemical venous thromboembolism
4. 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)
5. History of deep vein thrombosis, ischemic heart disease or stroke
6. Contraindications of tranexamic acid, floseal, or rivaroxaban
7. Allergy to tranexamic acid, floseal, rivaroxaban, or the excipients
8. History of heparin-induced thrombocytopenia (HIT)
9. Coagulopathy or bleeding tendency caused by organ dysfunction, such as cirrhosis, bone marrow suppression etc.
10. Patient who have active bleeding disorder, such as intracranial hemorrhage, upper GI bleeding, hematuria.
11. Patients with known allergies to materials of bovine origin

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combined topical TXA and Floseal	rivaroxaban (10mg)	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.
Topical TXA alone	rivaroxaban (10mg)	Intraarticular application of topical tranexamic acid after capsule closure Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.
Topical TXA alone	Topical tranexamic acid	Intraarticular application of topical tranexamic acid after capsule closure Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.
Combined topical TXA and Floseal	Topical tranexamic acid	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.
Combined topical TXA and Floseal	Floseal®	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.

Primary Outcome Measures

Name	Time	Method
Total Blood Loss After Operation	From the operation to the postoperative day 3 or 4	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Kaohsiung Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan