Extended Postoperative Oral Tranexamic Acid in Knee Replacement

Study Overview
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Brief Summary
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A comparison of outcomes between use of oral tranexamic acid as compared to oral placebo in the first days after total knee replacement will be made to determine impact on clinical indications and patient reported outcomes.

Detailed Description
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Significant blood loss occurs during total knee arthroplasty (TKA) which can lead to adverse outcomes including need for blood transfusion as well as increased local tissue swelling and ecchymosis which can inhibit post-operative recovery. Tranexamic acid (TXA), an inhibitor of fibrinolysis, has been shown to be a safe and effective drug for reducing blood loss during and after TKA. The use of TXA intraoperatively has been associated with higher postoperative hemoglobin levels and a reduction in postoperative blood transfusion rates. Administration of TXA in TKA has also been associated with improved clinical outcome measures including decreased rate of periprosthetic joint infection, decreased length of stay, and increased postoperative range of motion and early ambulation distances. However, there remains a wide variance in the route of administration, dosage, and timing of TXA use among treatment protocols in TKA. Previous studies have evaluated outcomes with the addition of post-operative TXA dosing to standard pre-operative and intra-operative intravenous (IV) doses. This study will investigate patient outcomes following a standardized post-operative oral TXA protocol as compared to oral placebo for three doses over day of surgery, postop day one and postop day two after TKA. Following written consent documentation, Subjects will be randomized and blinded to randomization assignment until completion of study to either the oral TXA group or oral placebo group. The study medication will be distributed with the Subject's name with instructions for use in the post-anesthesia unit (PACU). The first dose will be administered in PACU with subsequent doses to be taken at home on postop day one and postop day two. TKA will be completed in an ambulatory surgery center with discharge same day of surgery to home. Outcome measures include: Hemoglobin, visual analog score, KOOS Jr (Knee injury and osteoarthritis outcome score), range of motion, and incidence of treatment-emergent adverse event at postoperative (POD) day 3, POD week 2, POD week 6, and POD week 12. KOOS Jr. will be collected at one year post-op.

Official Title
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Extended Postoperative Tranexamic Acid Use in Primary Total Knee Arthroplasty: A Prospective, Randomized Controlled Trial

Conditions
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Knee Osteoarthritis, Blood Loss, Pain, Postoperative

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary total knee replacement in ambulatory setting Willing to participate Physical therapy on site at Campbell Clinic Wolf River Fluent in oral and written English Exclusion Criteria: Unwilling to participate Revision total knee replacement Preoperative use of anticoagulants other than 81 mg aspirin Previous history of thromboembolic event Previous history of cancer other than non-melanoma skin cancers

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral TXA<br>1,950 mg oral tranexmic acid (three capsules of 650 mg) administered in post-anesthesia care, postop day one and postop day two. Compounded by registered pharmacist and labeled with subject name and instructions for use. | Drug: Tranexamic Acid Pill<br>* 1950 mg tranexamic acid (three capsules) given in post-anesthesia room and three capsules for postop day one and three capsules for postop day two<br>|
| Placebo Comparator: Oral placebo<br>Three capsules of cellulose administered in post-anesthesia care, postop day one and postop day two. Compounded by registered pharmacist and labeled with subject name and instructions for use. | Drug: Placebo<br>* Three capsules of cellulose given in post-anesthesia room and three capsules for postop cay one and three capsules for postop day two<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin level | Hemoglobin enables red cells to transport oxygen and carbon dioxide in the blood and is measured in grams per deciliter with normal ranges of 12.0 to 17.5 | preoperative | 
| Hemoglobin level | Hemoglobin enables red cells to transport oxygen and carbon dioxide in the blood and is measured in grams per deciliter with normal ranges of 12.0 to 17.5 | postoperative hour 3 | 
| Hemoglobin level | Hemoglobin enables red cells to transport oxygen and carbon dioxide in the blood and is measured in grams per deciliter with normal ranges of 12.0 to 17.5 | postoperative day 3 | 
| Hemoglobin level | Hemoglobin enables red cells to transport oxygen and carbon dioxide in the blood and is measured in grams per deciliter with normal ranges of 12.0 to 17.5 | postoperative week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Score | Patient reported pain score from 0 to 10 where 0 is no pain and 10 is the most pain | preoperative | 
| Visual Analog Score | Patient reported pain score from 0 to 10 where 0 is no pain and 10 is the most pain | postoperative hour 3 | 
| Visual Analog Score | Patient reported pain score from 0 to 10 where 0 is no pain and 10 is the most pain | postoperative week 2 | 
| Visual Analog Score | Patient reported pain score from 0 to 10 where 0 is no pain and 10 is the most pain | postoperative week 6 | 
| Visual Analog Score | Patient reported pain score from 0 to 10 where 0 is no pain and 10 is the most pain | postoperative week 12 | 
| KOOS Jr Score | Patient reported outcome of how the knee feels from 0 to one 100 where 0 represents extreme problems and 100 represents no problems | preoperative | 
| KOOS Jr Score | Patient reported outcome of how the knee feels from 0 to one 100 where 0 represents extreme problems and 100 represents no problems | postoperative day 3 | 
| KOOS Jr Score | Patient reported outcome of how the knee feels from 0 to one 100 where 0 represents extreme problems and 100 represents no problems | postoperative week 2 | 
| KOOS Jr Score | Patient reported outcome of how the knee feels from 0 to one 100 where 0 represents extreme problems and 100 represents no problems | postoperative week 6 | 
| KOOS Jr Score | Patient reported outcome of how the knee feels from 0 to one 100 where 0 represents extreme problems and 100 represents no problems | postoperative week 12 | 
| KOOS Jr Score | Patient reported outcome of how the knee feels from 0 to one 100 where 0 represents extreme problems and 100 represents no problems | postoperative one year | 
| range of motion of knee | clinical measurement of passive, pain-free range of motion of knee in degrees from 0 to 180 from maximum extension to maximum flexion | preoperative | 
| range of motion of knee | clinical measurement of passive, pain-free range of motion of knee in degrees from 0 to 180 from maximum extension to maximum flexion | postoperative day 3 | 
| range of motion of knee | clinical measurement of passive, pain-free range of motion of knee in degrees from 0 to 180 from maximum extension to maximum flexion | postoperative week 2 | 
| range of motion of knee | clinical measurement of passive, pain-free range of motion of knee in degrees from 0 to 180 from maximum extension to maximum flexion | postoperative week 6 | 
| range of motion of knee | clinical measurement of passive, pain-free range of motion of knee in degrees from 0 to 180 from maximum extension to maximum flexion | postoperative week 12 |