Osteoarthritis, Knee
Conditions
Keywords
Tranexamic Acid, Total Knee Arthroplasty, Rivaroxaban
Brief summary
The aim of this study was to conduct a prospective, randomized, double-blind study and assess the efficacy of and safety for thromboprophylaxis of rivaroxaban in total knee arthroplasty patients when tranexamic acid is used for bleeding prophylaxis.
Detailed description
Total knee arthroplasty is an effective procedure for end-stage arthritis of the knee in terms of pain relief and functional recovery. However, this procedure is associated with a substantial perioperative blood loss. As high as 69% allogeneic blood transfusion rate was reported in patients receiving total knee arthroplasty when preoperative haemoglabin level was \<13 g/dl. Tranexamic acid (TXA), an antifibrinolytic, given intraoperatively, has been reported to be effective in reducing one third of postoperative blood loss in standard total knee arthroplasty. Our previous study showed that TXA reduced total blood loss from 1453mL to 833mL (p\<0.001) and the need for transfusion from 20% to 4% (p=0.014) in total knee patients with enoxaparin (Clexane; Glaxo-Smith-Kline, Brentford, United Kindom) for thromboprophylaxis. In recent years, there have been more effective and practical methods for thrombophylaxis in total hip and knee replacement surgeries. Rivaroxaban is one of the first oral factor Xa inhibitors licensed for this regard. The advantages of rivaroxaban include oral administration, no need to monitor blood levels and no dosing adjustments which are convenient for short hospital stay in contemporary total knee arthroplasty. Its efficacy in preventing venous thromboembolism (VTE) after total knee arthroplasty have been extensitvely investigated in RECORD (Regulation of Coagulation in Orthopaedic surgery to prevent Deep-vein thrombosis and pulmonary embolism) 3 and 4 studies, and the results showed that rivaroxaban 10mg once daily was superior to enoxaparin 40mg subcutaneously once daily or 30mg every 12 hours for 10 to 14 days. Despite of its clinical efficacy in VTE prophylaxis, orthopaedic surgeons are still sceptic in routine use of rivaroxaban in knee and hip surgery and concerned about the increased risk of bleeding complications. A higher reoperation rate regarding wound complications within 30 days of hip and knee replacement in the rivaroxaban group than the tinzaparin group (2.94% versus 1.8%) was reported recently. Similar event has been reported in other studies. However, all these studies did not use TXA as bleeding prophylaxis after hip and knee replacement surgery. The risk of increasing VTE by use of TXA, owing to its antifibrinolytic effects, is the cause of concern. The aim of this study was to conduct a prospective, randomized, double-blind study and assess the efficacy of and safety for thromboprophylaxis of rivaroxaban in total knee arthroplasty patients when TXA is used for bleeding prophylaxis.
Interventions
DRUGTranexamic Acid 5%,5ml/amp (intraoperative)
tranexamic acid 1g administered intravenously five minutes before deflation of the tourniquet
DRUGTranexamic Acid 5%,5ml/amp (3 hours after operation)
tranexamic acid 1g administered intravenously 3 hours after operation
DRUG0.9% Normal Saline (intraoperative)
0.9% Normal Saline 20ml administered intravenously five minutes before deflation of the tourniquet
DRUG0.9% Normal Saline (3 hours after operation)
0.9% Normal Saline 20ml administered intravenously 3 hours after operation
Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence 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 ) | Primary efficacy outcome is the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality |
| Incidence of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings | within 15 days after surgery (2 days after the last dose of rivaroxaban ) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary safety outcome was composite of any non-major bleeding and all wound complications after operation | within 15 days after surgery (2 days after the last dose of rivaroxaban | Non-major bleeding including hemorrhagic wound complications (excessive wound hematoma or bleeding at the surgical site |
| Total blood loss after surgery | From the operation to the postoperative day 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 |
| Incidence of wound complications after surgery | within 30 days of the procedure | composite of hematoma, superficial wound infection, and deep infection requiring return to surgery |
| Incidence of major venous thromboembolism | within 15 days after surgery (2 days after the last dose of rivaroxaban | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of venographic positive deep-vein thrombosis (any, proximal, distal) | on the second day after last dose of rivaroxaban (POD 15) | — |
| Incidence of positive finding of pulmonary embolism by computed tomography | on the second day after last dose of rivaroxaban (POD 15) | In case of suspected pulmonary embolism, computed tomography of the chest was performed |
Countries
Taiwan
Outcome results
None listed