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

Phase 4

Completed

Conditions: Osteoarthritis, Knee

Interventions: Drug: Topical tranexamic acid
Drug: Intravenous tranexamic acid
Drug: Intravenous saline
Drug: Topical saline

Registration Number: NCT02540226

Lead Sponsor: Hospital for Special Surgery, New York

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 76

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Topical tranexamic acid	Intravenous saline	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.
Topical tranexamic acid	Topical tranexamic acid	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.
Intravenous tranexamic acid	Intravenous tranexamic acid	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.
Intravenous tranexamic acid	Topical saline	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation	before cementing, 1 hour after tourniquet release, 4 hours after tourniquet release	Systemic PAP blood level measured at the following time points - Intraoperative - 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	4 hours after tourniquet release	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.
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	Intraoperative, 1 hour post Tourniquet Release (TQR)	Levels of PAP will be measured in peripheral blood and wound drainage
Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation in Wound Blood	Intraoperative, 4 hour post Tourniquet Release (TQR)	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.