Serial Use of Intravenous and Oral Tranexamic Acid in Primary Total Knee Arthroplasty Patients

Sponsor

Seoul National University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03109652

Collaborator

(none)

144

Enrollment

Location

Arms

18.8

Anticipated Duration (Months)

7.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The usefulness of tranexamic acid(TXA) to reduce blood loss and transfusion in total knee replacement arthroplasty(TKRA) has been demonstrated. However, the optimal does, duration of treatment and route of administration of TXA to reduce blood loss while minimizing adverse effects remain uncertain. Recently, the serial use of perioperative IV and post-operative oral TXA has been shown to significantly reduce transfusion rate without increasing thromboembolic complications compared to placebo. The aim of this study is to 1) determine the beneficial effect and safety of the serial treatment of IV and oral TXA over IV use alone and 2) assess the sufficient length of postoperative use of oral TXA in TKRA patients.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	Drug: Tranexamic Acid	Phase 4

Detailed Description

It has been demonstrated that tranexamic acid (TXA) reduces the peri-operative blood loss as well as the need for transfusion in total knee replacement arthroplasty(TKRA). The anti-fibrinolytic effects of TXA have been shown to mainly present in the wound that, in previous studies, the use of TXA decreased the blood loss without increasing the risk of thromboembolic complications. Nevertheless, the optimal dose, duration of treatment and route of administration of TXA to reduce blood loss while minimizing adverse effects remain uncertain.

To use TXA as a pharmacologic alternative to transfusion, optimal regimen should be elucidated. Various studies have reported the effect of perioperative use of intravenous or topical TXA. Meta-analyses concluded that combined use of intravenous and topical TXA is more effective in reducing the blood loss and transfusion rate without increasing the risk of deep vein thrombosis or pulmonary embolism compared to the use of either intravenous TXA or topical TXA alone. Both intravenous and topical administration was conducted pre or intraoperatively or within 6 hours post-operatively mainly due to conceivable risk of thromboembolic event when TXA is used continuously after surgery. However, regarding the fact that systemic activation of fibrinolysis starts post-operatively in TKRA using tourniquets and lasts over 18 hours, the continuous use of TXA after surgery might have additional benefit over the single day use. Moreover, the serial use of post-operative oral TXA for 5 days after perioperative IV TXA use has been shown to significantly reduce transfusion rate without increasing thromboembolic complications compared to placebo.

Therefore, in this study, the investigators aimed to 1) investigate the effect of serial use of perioperative IV and post-operative oral TXA in reducing the blood loss and transfusion risk compared to single day perioperative use of IV TXA and 2) assess the sufficient length of postoperative use of oral TXA in TKRA patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Serial Use of Intravenous and Oral Tranexamic Acid in Primary Total Knee Arthroplasty Patients: A Randomized Controlled Study

Actual Study Start Date :

Jul 10, 2017

Anticipated Primary Completion Date :

Feb 1, 2019

Anticipated Study Completion Date :

Feb 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: IV TXA alone One ampule of 500mg/ml tranexamic acid(TXA) inj is injected intravenously during operation after box cutting procedure(before tourniquet deflation). Additionally, 1 ampule of TXA is administrated 3 hours after first injection on the day of operation.	Drug: Tranexamic Acid On the day of operation, same dose of IV tranexamic acid(TXA) is given to all subjects in three study groups. Oral TXA is given from postoperative day 1 only to experimental groups. Duration of oral TXA administration is different between two experimental groups. (5 days in "IV TXA and Oral TXA 5 days group" and 2 days in "IV TXA and Oral TXA 2 days group")
Experimental: IV TXA and Oral TXA 5 days One ampule of 500mg/ml tranexamic acid(TXA) inj is injected intravenously during operation after box cutting procedure(before tourniquet deflation). Additionally, 1 ampule of TXA is administrated 3 hours after first injection on the day of operation. Two 250mg capsules of oral TXA(Transamin Cap) is given three times a day, 30 minutes after each meal, from postoperative day 1 to day 5.	Drug: Tranexamic Acid On the day of operation, same dose of IV tranexamic acid(TXA) is given to all subjects in three study groups. Oral TXA is given from postoperative day 1 only to experimental groups. Duration of oral TXA administration is different between two experimental groups. (5 days in "IV TXA and Oral TXA 5 days group" and 2 days in "IV TXA and Oral TXA 2 days group")
Experimental: IV TXA and Oral TXA 2 days One ampule of 500mg/ml tranexamic acid(TXA) inj is injected intravenously during operation after box cutting procedure(before tourniquet deflation). Additionally, 1 ampule of TXA is administrated 3 hours after first injection on the day of operation. Two 250mg capsules of oral TXA(Transamin Cap) is given three times a day, 30 minutes after each meal, from postoperative day 1 to day 2.	Drug: Tranexamic Acid On the day of operation, same dose of IV tranexamic acid(TXA) is given to all subjects in three study groups. Oral TXA is given from postoperative day 1 only to experimental groups. Duration of oral TXA administration is different between two experimental groups. (5 days in "IV TXA and Oral TXA 5 days group" and 2 days in "IV TXA and Oral TXA 2 days group")

Arm

Intervention/Treatment

Active Comparator: IV TXA alone

Drug: Tranexamic Acid

On the day of operation, same dose of IV tranexamic acid(TXA) is given to all subjects in three study groups. Oral TXA is given from postoperative day 1 only to experimental groups. Duration of oral TXA administration is different between two experimental groups. (5 days in "IV TXA and Oral TXA 5 days group" and 2 days in "IV TXA and Oral TXA 2 days group")

Experimental: IV TXA and Oral TXA 5 days

One ampule of 500mg/ml tranexamic acid(TXA) inj is injected intravenously during operation after box cutting procedure(before tourniquet deflation). Additionally, 1 ampule of TXA is administrated 3 hours after first injection on the day of operation. Two 250mg capsules of oral TXA(Transamin Cap) is given three times a day, 30 minutes after each meal, from postoperative day 1 to day 5.

Drug: Tranexamic Acid

Experimental: IV TXA and Oral TXA 2 days

Drug: Tranexamic Acid

Outcome Measures

Primary Outcome Measures

Change from preoperative hemoglobin at day 2 [Preop. day 1 to postop. day 2]
Hemoglobin (g/dL)
Change from preoperative hemoglobin at day 6 [Preop. day 1 to postop. day 6]
Hemoglobin (g/dL)

Secondary Outcome Measures

Transfusion rate and amount [Postoperative day 0 to day 6]
transfusion trigger: packed red blood cell(RBC) 1 pack is given if Hb < 7 or 7 ≤ Hb< 8 with symptom of anemia
Complications [up to 6 week after operation]
CT angiography on postoperative day 6 for evaluation of deep vein thrombosis, Pulmonary embolism, superficial or deep infection, and other complications are assessed clinically.
Calculated Blood loss [Postop. day 6]
Based on predicted blood volume and hemoglobin balance

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Candidate for total knee replacement arthroplasty due to osteoarthritis of the knee.

Exclusion Criteria:

Known allergic reaction to tranexamic acid
Secondary arthritis (ex. Rheumatic arthritis, traumatic arthritis, septic arthritis)
History of thromboembolic event including deep vein thrombosis, pulmonary embolism, cerebral infarction, transient ischemic attack, myocardial infarction, angina
Premenopausal female
Known congenital or acquired coagulopathy
Currently in treatment with Adenosine disphosphate receptor inhibitors, Vitamin K antagonist, Factor Xa inhibitor, Direct thrombin inhibitor or Heparin
Aspirin administration within 5 days before operation
Preoperative Prothrombin time(PT) international normalized ratio(INR) > 1.4
Severe systemic comorbidities of American Society of Anesthesiology (ASA) grade 4 including heart failure, renal failure, hepatic failure, pulmonary disease and cancer
Do not agree to participate in the study