The Effect of Tranexamic Acid on Blood Coagulation in Total Hip Arthroplasty Surgery

Study Overview
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Brief Summary
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Total hip arthroplasty (THA) is associated with blood loss ranging from 300 to 2000 mL. Tranexamic acid (TXA) is frequently administered prophylactically during this procedure to reduce blood loss by inhibiting fibrinolysis or by stopping naturally occurring clot resolution. TXA is employed currently based on a surgeon's preference. The objective of this study is to quantitate the degree of fibrinolysis using rotational thromboelastometry (ROTEM) and investigate the role of TXA prophylaxis on blood loss in patients undergoing THA in a double-blind fashion. Our hypothesis is that fibrinolysis is minimal at most and TXA prophylaxis is not necessary during THA. All patients, whether they receive TXA or normal saline, will not be at risk, as at this time no data exists to determine which approach is safer or more effective. This is the first study to compare TXA vs. placebo in a double-blinded, randomized controlled trial.

Detailed Description
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Total hip arthroplasty (THA) is associated with moderate blood loss ranging from 300 to 2000 mL. Tranexamic acid (TXA) is frequently administered prophylactically during this procedure to reduce blood loss by inhibiting fibrinolysis. Most clinical studies reported potential benefit of the treatment demonstrated by less estimated blood loss (EBL), reduced hemoglobin/hematocrit (HH) change, and reduced transfused packed red blood cells (PRBC). However, bleeding complication may be affected more significantly by the degree of surgical trauma and comorbidity of patients than coagulation abnormality. Further, the frequency and severity of fibrinolysis during these procedures have not been well studied. Additionally, TXA administration may increase the tendency of postoperative venous thrombosis by inhibiting fibrinolysis in already prothrombotic patients. The objective of this study is to quantitate the degree of fibrinolysis using rotational thromboelastometry (ROTEM) and investigate the role of TXA prophylaxis on clinical outcome in patients undergoing THA in a double-blind fashion. Our hypothesis is that fibrinolysis is minimal at most and TXA prophylaxis is not necessary during primary THA.

Official Title
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The Effect of Tranexamic Acid on Blood Coagulation in Total Hip Arthroplasty Surgery Based on Rotational Thromboelastometry (ROTEM®).

Conditions
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Tranexamic Acid, Coagulation; Intravascular, Rotational Thromboelastometry, Fibrinolysis; Hemorrhage, Total Hip Arthroplasty

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study population will include total of 200 adults (age range of 18 - 85 years) who are in the American Society of Anesthesiologists (ASA) Physical Status (PS) 1-3. Inclusion criteria are patients undergoing unilateral, primary, total hip arthroplasty. Exclusion Criteria: Exclusion criteria include patient's refusal, patients with history of significant coagulopathy or on anticoagulation therapy. Female patients who are pregnant or nursing will be excluded. In addition, patients with anemia (Hb < 8 g/dL) or who received blood transfusion within one week before surgery will be excluded. Patient receiving subcutaneous heparin on the same day prior to surgery will be also excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: double-blinded randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tranexamic acid<br>Patients undergoing unilateral, primary, total hip arthroplasty with English as their native language | Drug: Tranexamic Acid<br>* tranexamic acid will be administered intravenously after induction of anesthesia (a bolus of 10 mg/kg or maximal dose of 1g).<br>|
| Placebo Comparator: Normal saline<br>Patients undergoing unilateral, primary, total hip arthroplasty with English as their native language | Drug: Placebo<br>* Patients in the placebo group will receive normal saline (a bolus of sodium chloride 0.9%, 0.1 mL/kg or maximal dose of 10 mL).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibrinolysis | Fibrinolysis based on ROTEM parameter, defined as ML (maxium lysis) >15% | after induction of anesthesia (baseline), | 
| Fibrinolysis | Fibrinolysis based on ROTEM parameter, defined as ML (maxium lysis) >15% | 45 min after drug administration, | 
| Fibrinolysis | Fibrinolysis based on ROTEM parameter, defined as ML (maxium lysis) >15% | one hour after the end of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood loss | amount of blood loss in milliliter during surgery | during surgery (intraoperative) | 
| blood transfusion | Amount of Packed Red Blood Cells (PRBC) transfused | Intraoperative and up to 72-hour after surgery | 
| pre- and postoperative hemoglobin level | Pre and postoperative hemoglobin level in grams per deciliter | up to 72-hour after surgery | 
| Wound infection | Incidence of wound infection | up to 72-hour after surgery | 
| Hematoma | Incidence of hematoma | up to72-hour after surgery | 
| Thrombotic events (PE, DVT). | Incidence of thrombotic events (pulmonary embolism, deep vein thrombosis) | up to 72-hour after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tranexamic acid, Rotational thromboelastometry, Fibrinolysis, viscoelastic essay