Effect of Topical and Intravenous Tranexamic Acid (TXA) on Thrombogenic Markers in Patients Undergoing Knee Replacement

Study Overview
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Brief Summary
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Tranexamic acid (TXA) is a drug that is being used more frequently at the Hospital for Special Surgery to lessen the amount of blood loss after total knee replacement (TKR). It is an anti-fibrinolytic agent, which means that it promotes the formation of blood clots. TXA can be given either intravenously or topically (placed directly on the open wound) before wound closure. Patients with certain medical conditions have been found to have a high risk of thrombosis after being given intravenous TXA, which may lead to serious complications. However, to date, no high-risk patients have been identified for use of topical TXA. This study will look at thrombogenic markers (proteins found in blood that promote clot formation) after TXA is given either intravenously or topically. If the effect on these markers is similar between intravenous and topical use of TXA, then the safety of topical TXA should be questioned. Of note, these markers have never been measured after TXA has been given topically. As a result, this information would be important for the medical community.

Official Title
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The Effect of Topical and Intravenous Tranexamic Acid (TXA) on Thrombogenic Markers in Patients Undergoing Total Knee Replacement

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Intravenous tranexamic acid
* Drug: Topical tranexamic acid
* Drug: Intravenous saline
* Drug: Topical saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing primary unilateral total knee replacement with a participating surgeon Patients aged 18-80 Exclusion Criteria: All patients on steroid therapy regardless of dose, duration, or treatment or those requiring stress-dose steroids preoperatively Patients who will require postoperative use of Coumadin, Xarelto, or Plavix Use of non-steroidal anti-inflammatory drugs (NSAIDs) within 1 week of surgery Hypersensitivity to tranexamic acid Renal dysfunction (Creatinine clearance < 40 ml/min) Hepatic dysfunction (AST or ALT 2x upper limit of normal) Cardiac exclusions: coronary stent, history of myocardial infarction, positive stress test, atrial fibrillation, advanced coronary artery disease Advanced chronic obstructive pulmonary disease or advanced interstitial lung disease History of venous thromboembolism Hypercoagulability (e.g. antiphospholipid syndrome, genetic hypercoagulability with or without prior venous thromboembolism) History of stroke or transient ischemic attack

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous tranexamic acid<br>Patients will receive 1g tranexamic acid in 100mL solution intravenously in the operating room before inflation of the tourniquet. They will again receive the same IV solution in the post-anesthesia care unit, approximately 3 hours after the first solution was given. They will also receive a 75cc topical saline solution approximately 5 minutes before the tourniquet is released. | Drug: Intravenous tranexamic acid<br> <br> Drug: Topical saline<br> <br> |
| Experimental: Topical tranexamic acid<br>Patients will receive 3g tranexamic acid in 75mL solution topically in the operating room, approximately 5 minutes before the tourniquet is released. It will sit for 5 minutes before the solution is suctioned off by the surgeon. They will also receive 2 intravenous saline solutions: one in the operating room before inflation of the tourniquet, and one in the post-anesthesia care unit 3 hours after the first solution was given. | Drug: Topical tranexamic acid<br> <br> Drug: Intravenous saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Plasmin Anti-plasmin (PAP) - Marker of Fibrinolysis | Levels of PAP will be measured in peripheral blood and wound drainage at 4 hours after tourniquet release. | 4 hours after tourniquet release | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation | Systemic PAP blood level measured at the following time points - Intraoperative - Before cementing, 1 hour after tourniquet release, 4 hours after tourniquet release | before cementing, 1 hour after tourniquet release, 4 hours after tourniquet release | 
| Levels of Tranexamic Acid |  | Intraoperative (before cementing), 1 hour after tourniquet release (TQR), 4 hours after tourniquet release(TQR) | 
| Calculated Postoperative Blood Loss |  | Duration of inpatient hospital stay (average of 3 days) | 
| Levels of Hemoglobin |  | 1 hour after tourniquet release, POD 1, POD 2 | 
| Levels of Hematocrit |  | 1 hour after tourniquet release, POD 1, POD 2 | 
| Constavac Blood Drainage | A wound drain is connected to a Constavac system, which postoperatively collects, filters, and allows for reinfusion of the patient's own blood. Shed blood passes through an internal prefilter and is collected in a reservoir. | 4 hours after tourniquet release | 
| Incidence of Thrombosis (DVT/PE) |  | Postoperative day 14 (2 weeks after surgery) | 
| Patients Who Had 1 Unit of Blood Transfusion Administered |  | Duration of inpatient hospital stay (average of 3 days) | 
| Time to Physical Therapy Discharge |  | During Hospital Stay | 
| Length of Hospital Stay |  | Length of Hospital Stay | 
| Levels of IL-6 in Blood |  | Intraoperative, 1 hour post Tourniquet Release (TQR), 4 hour post Tourniquet Release (TQR) | 
| Levels of Plasmin Anti-plasmin (PAP) - Marker of Fibrinolysis | Levels of PAP will be measured in peripheral blood and wound drainage | Intraoperative, 1 hour post Tourniquet Release (TQR) | 
| Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation in Wound Blood | The values for the wound blood levels are given as the count of patients who had a level above the threshold of >3600 pmol/L. | Intraoperative, 4 hour post Tourniquet Release (TQR) | 

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