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

Phase 4
Conditions
Knee Osteoarthritis
Interventions
Registration Number
NCT03109652
Lead Sponsor
Seoul National University Hospital
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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
144
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IV TXA aloneTranexamic AcidOne 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.
IV TXA and Oral TXA 5 daysTranexamic AcidOne 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.
IV TXA and Oral TXA 2 daysTranexamic AcidOne 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.
Primary Outcome Measures
NameTimeMethod
Change from preoperative hemoglobin at day 2Preop. day 1 to postop. day 2

Hemoglobin (g/dL)

Change from preoperative hemoglobin at day 6Preop. day 1 to postop. day 6

Hemoglobin (g/dL)

Secondary Outcome Measures
NameTimeMethod
Calculated Blood lossPostop. day 6

Based on predicted blood volume and hemoglobin balance

Transfusion rate and amountPostoperative 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

Complicationsup 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.

Trial Locations

Locations (1)

Seoul National University Boramae Medical Center

🇰🇷

Seoul, Dongjak Gu, Korea, Republic of

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