Does Early Administration of Tranexamic Acid Reduce Blood Loss and Perioperative Transfusion Requirement

Study Overview
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Brief Summary
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Intertrochanteric hip fractures typically result in blood loss from the fracture and require surgery that can cause further blood loss. This study is being done to look at a medication called tranexamic acid which may reduce blood loss and the need for blood transfusions associated with surgery.

Detailed Description
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The use of TXA in orthopedic trauma patients is an area of current research interest. A 2010 prospective randomized, controlled trial of perioperative TXA demonstrated reduction in transfusion requirements for intertrochanteric hip fractures treated with short, cephalomedullary nails. This was clinically, though not statistically, significant. Investigators recently conducted a randomized, controlled trial at this institution to evaluated the use of TXA in patients with femoral neck fractures treated with hemiarthroplasty or total hip arthroplasty and found clinically, albeit not statistically, significant reduction in transfusion requirement (accepted for publication). Perhaps tempering the effect seen with perioperative administration of TXA is the blood loss that occurs prior to surgery, the so-called hidden blood loss that can be as substantial as 1/3 of total blood loss from a hip fracture. This raises the question whether administration of tranexamic acid at the time of initial presentation after fracture could improve the perioperative care of these patients by decreasing the proportion of patients requiring transfusion and decreasing total blood loss.

Official Title
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Does Early Administration of Tranexamic Acid Reduce Blood Loss and Perioperative Transfusion Requirement in Low Energy Hip Fracture Patients?

Conditions
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Hip Fractures, Intertrochanteric Fractures

Intervention / Treatment
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* Drug: Tranexamic Acid (TXA)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AO/OTA fracture classification 31A Surgically treated with sliding hip screw or cephalomedullary nail (short or long) Low energy, isolated injury Exclusion Criteria: Intracapsular hip fractures: AO/OTA fracture classification 31B-C Polytrauma patients Creatinine clearance less than 30 mL/min History of unprovoked VTE and/or recurrent VTE Known history of Factor V Leiden, protein C/S deficiency, prothrombin gene mutation, anti-thrombin deficiency, anti-phospholipid antibody syndrome, lupus anticoagulant Pregnancy or breastfeeding (pregnancy tests will be performed on all patients of child-bearing potential) History of CVA, MI, or VTE within the previous 30 days Coronary stent placement within the previous 6 months Disseminated intravascular coagulation Intracranial hemorrhage

Ages Eligible for Study
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Minimum Age: 18 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: Subjects will be randomized into one of two study groups: TXA administration (treatment) or placebo (control). In order to ensure balance on the subject demographics between the two study groups, the subjects will be stratified on gender, age group (<75 vs. ≥75) and body mass index (<30 vs. ≥30). Within each stratum, subjects will be assigned to either the treatment group or control group using an electronic dynamic allocation program housed in a computer application developed by personnel in the Division of Biomedical Statistics and Informatics.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tranexamic Acid Arm (TXA)<br>Subjects will be treated with early administration of TXA in the Emergency Department | Drug: Tranexamic Acid (TXA)<br>* Intravenously via bolus dose of 1g over ten minutes and an additional 1g over the subsequent 8 hours<br>* Other names: Cyklokapron;|
| Placebo Comparator: Control Arm<br>Subjects will be treated with a placebo in the Emergency Department | Drug: Placebo<br>* Looks exactly like the study drug, but it contains no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Transfused at Least 1 Unit of Packed Red Blood Cells | Transfusion will be considered for all patients with hemoglobin values of less than 8 g/dL with persistent symptoms or history of significant cardiac disease that may render the patient less able to compensate for significant anemia. Blood transfusion will be considered in all patients with hemoglobin less than 7 g/dL, regardless of symptoms. | Length of hospitalization (approximately 3 to 5 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Units of Packed Red Blood Cells Transfused | Number of units of packed red blood cells transfused per patient | Length of hospitalization (approximately 3 to 5 days) | 
| Calculated Blood Loss | Total blood loss per patient measured in milliliters (mL) | Length of hospitalization (approximately 3 to 5 days) | 
| Number of Subjects to Experience Symptomatic Venous Thromboembolism (VTE) | Number of subjects to experience symptomatic Venous Thromboembolism (VTE) | Within 6 months of surgery | 
| Wound Complications | Number of subjects diagnosed with a wound complication | Within 6 months of surgery | 
| (Myocardial Infarction) MI Diagnosed | Number of subjects diagnosed with a myocardial infarction | Within 6 months of surgery | 
| Cerebrovascular Accident (CVA) Diagnosed | Number of subjects diagnosed with a cerebrovascular accident | Within 6 months of surgery | 
| All-cause Mortality | Number of subject deaths | At 6 months after surgery |