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

Knee Osteoarthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03109652
• Other study ID #: SNUBMC_2017001
• Status: Recruiting
• Phase: Phase 4
• Start date: July 10, 2017
• Est. completion date: February 2019

Study information

• Verified date: January 2019
• Source: Seoul National University Hospital
• Contact: Seung-Baik Kang, MD, PhD
• Phone: +82-870-3931
• Email: ossbkang[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: February 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

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")

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Boramae Medical Center	Seoul	Dongjak Gu

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (13)

Alshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM. Tranexamic acid in total knee replacement: a systematic review and meta-analysis. J Bone Joint Surg Br. 2011 Dec;93(12):1577-85. doi: 10.1302/0301-620X.93B12.26989. Review. — View Citation

Benoni G, Lethagen S, Fredin H. The effect of tranexamic acid on local and plasma fibrinolysis during total knee arthroplasty. Thromb Res. 1997 Feb 1;85(3):195-206. Erratum in: hromb Res 1997 Oct 15;88(2):251. — View Citation

Blanié A, Bellamy L, Rhayem Y, Flaujac C, Samama CM, Fontenay M, Rosencher N. Duration of postoperative fibrinolysis after total hip or knee replacement: a laboratory follow-up study. Thromb Res. 2013 Jan;131(1):e6-e11. doi: 10.1016/j.thromres.2012.11.006. Epub 2012 Nov 26. — View Citation

Cankaya D, Dasar U, Satilmis AB, Basaran SH, Akkaya M, Bozkurt M. The combined use of oral and topical tranexamic acid is a safe, efficient and low-cost method in reducing blood loss and transfusion rates in total knee arthroplasty. J Orthop Surg (Hong Kong). 2017 Jan;25(1):2309499016684725. doi: 10.1177/2309499016684725. — View Citation

Charoencholvanich K, Siriwattanasakul P. Tranexamic acid reduces blood loss and blood transfusion after TKA: a prospective randomized controlled trial. Clin Orthop Relat Res. 2011 Oct;469(10):2874-80. doi: 10.1007/s11999-011-1874-2. Epub 2011 Apr 22. — View Citation

Irwin A, Khan SK, Jameson SS, Tate RC, Copeland C, Reed MR. Oral versus intravenous tranexamic acid in enhanced-recovery primary total hip and knee replacement: results of 3000 procedures. Bone Joint J. 2013 Nov;95-B(11):1556-61. doi: 10.1302/0301-620X.95B11.31055. — View Citation

Li JF, Li H, Zhao H, Wang J, Liu S, Song Y, Wu HF. Combined use of intravenous and topical versus intravenous tranexamic acid in primary total knee and hip arthroplasty: a meta-analysis of randomised controlled trials. J Orthop Surg Res. 2017 Feb 2;12(1):22. doi: 10.1186/s13018-017-0520-4. — View Citation

Lin C, Qi Y, Jie L, Li HB, Zhao XC, Qin L, Jiang XQ, Zhang ZH, Ma L. Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: A meta-analysis. Medicine (Baltimore). 2016 Dec;95(51):e5344. doi: 10.1097/MD.0000000000005344. Review. — View Citation

Nielsen CS, Jans Ø, Ørsnes T, Foss NB, Troelsen A, Husted H. Combined Intra-Articular and Intravenous Tranexamic Acid Reduces Blood Loss in Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial. J Bone Joint Surg Am. 2016 May 18;98(10):835-41. doi: 10.2106/JBJS.15.00810. — View Citation

Pilbrant A, Schannong M, Vessman J. Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol. 1981;20(1):65-72. — View Citation

Reikerås O, Clementsen T. Time course of thrombosis and fibrinolysis in total knee arthroplasty with tourniquet application. Local versus systemic activations. J Thromb Thrombolysis. 2009 Nov;28(4):425-8. doi: 10.1007/s11239-008-0299-6. Epub 2008 Dec 6. — View Citation

Wang H, Shen B, Zeng Y. Comparison of topical versus intravenous tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized controlled and prospective cohort trials. Knee. 2014 Dec;21(6):987-93. doi: 10.1016/j.knee.2014.09.010. Epub 2014 Oct 23. Review. — View Citation

Wu Q, Zhang HA, Liu SL, Meng T, Zhou X, Wang P. Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials. Eur J Orthop Surg Traumatol. 2015 Apr;25(3):525-41. doi: 10.1007/s00590-014-1568-z. Epub 2014 Nov 28. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from preoperative hemoglobin at day 2	Hemoglobin (g/dL)	Preop. day 1 to postop. day 2
Primary	Change from preoperative hemoglobin at day 6	Hemoglobin (g/dL)	Preop. day 1 to postop. day 6
Secondary	Transfusion rate and amount	transfusion trigger: packed red blood cell(RBC) 1 pack is given if Hb < 7 or 7 = Hb< 8 with symptom of anemia	Postoperative day 0 to day 6
Secondary	Complications	CT angiography on postoperative day 6 for evaluation of deep vein thrombosis, Pulmonary embolism, superficial or deep infection, and other complications are assessed clinically.	up to 6 week after operation
Secondary	Calculated Blood loss	Based on predicted blood volume and hemoglobin balance	Postop. day 6