Osteoarthritis, Knee
Conditions
Keywords
Thrombin-gelatin matrix, Floseal, Tranexamic Acid, Total Knee Arthroplasty
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.
Interventions
Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule
DRUGFloseal®
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)
Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Taiwan
Participant flow
Recruitment details
Between September 2017 and September 2018, a consecutive series of 125 patients who underwent unilateral TKA were assessed in terms of their eligibility for inclusion for this study. 35 patients were excluded based on the exclusion criteria, eight patients did not withhold antiplatelet drugs or anticoagulants 7 days before surgery, and 12 other patients declined to participate in the study. Total 70 patients were enrolled and randomly assigned into 2 groups
Participants by arm
| Arm | Count |
|---|---|
| Combined Topical TXA and 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.
Topical tranexamic acid: Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule
Floseal®: 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)
rivaroxaban (10mg): Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14. | 35 |
| Topical TXA Alone Intraarticular application of topical tranexamic acid after capsule closure Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.
Topical tranexamic acid: Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule
rivaroxaban (10mg): Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14. | 34 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Topical TXA Alone | Total | Combined Topical TXA and Floseal |
|---|---|---|---|
| Age, Continuous | 67.47 years STANDARD_DEVIATION 4 | 68.38 years STANDARD_DEVIATION 4.32 | 69.26 years STANDARD_DEVIATION 5.88 |
| Body mass index | 27.44 kg/m^2 STANDARD_DEVIATION 4.44 | 28.07 kg/m^2 STANDARD_DEVIATION 4.11 | 28.69 kg/m^2 STANDARD_DEVIATION 3.77 |
| Preop Hb | 13.39 g/dL STANDARD_DEVIATION 0.85 | 13.61 g/dL STANDARD_DEVIATION 1.03 | 13.79 g/dL STANDARD_DEVIATION 1.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 34 Participants | 69 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 34 participants | 69 participants | 35 participants |
| Sex: Female, Male Female | 29 Participants | 53 Participants | 24 Participants |
| Sex: Female, Male Male | 5 Participants | 16 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 34 |
| other Total, other adverse events | 17 / 35 | 15 / 34 |
| serious Total, serious adverse events | 0 / 35 | 0 / 34 |
Outcome results
Primary
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
Time frame: From the operation to the postoperative day 3 or 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Topical TXA and Floseal | Total Blood Loss After Operation | 678 ml | Standard Deviation 203 |
| Topical TXA Alone | Total Blood Loss After Operation | 733 ml | Standard Deviation 217 |
p-value: 0.276t-test, 2 sided
Secondary
Blood Transfusion Rate
We will record the event of blood transfusion, and calculate the incidence of transfusion
Time frame: From the operation to the postoperative day 3 or 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Topical TXA and Floseal | Blood Transfusion Rate | 1 Participants |
| Topical TXA Alone | Blood Transfusion Rate | 0 Participants |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Incidence of Thrombosis Events
The composite of any venous thromoembolism events, ischemic heart attacks, cerebrovascular accidents
Time frame: within 30 days of the operation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Topical TXA and Floseal | Incidence of Thrombosis Events | 0 Participants |
| Topical TXA Alone | Incidence of Thrombosis Events | 0 Participants |
p-value: 1Wilcoxon (Mann-Whitney)