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

NCT03109652 | Unknown Phase 4

• 1 other identifier: SNUBMC_2017001
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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.

Conditions

Knee Osteoarthritis

Keywords

total knee replacement arthroplasty; total knee arthroplasty; tranexamic acid; oral tranexamic acid; transfusion; blood loss

Outcome Measures

Primary Outcomes (2)

• Change from preoperative hemoglobin at day 2

  Hemoglobin (g/dL)

  Preop. day 1 to postop. day 2

• Change from preoperative hemoglobin at day 6

  Hemoglobin (g/dL)

  Preop. day 1 to postop. day 6

Secondary Outcomes (3)

• Transfusion rate and amount

  Postoperative day 0 to day 6

• Complications

  up to 6 week after operation

• Calculated Blood loss

  Postop. day 6

Study Arms (3)

IV TXA alone

ACTIVE COMPARATOR

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

IV TXA and Oral TXA 5 days

EXPERIMENTAL

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

IV TXA and Oral TXA 2 days

EXPERIMENTAL

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

Interventions

Tranexamic Acid DRUG

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")

IV TXA alone; IV TXA and Oral TXA 2 days; IV TXA and Oral TXA 5 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Boramae Medical Center

Seoul, Dongjak Gu, 07061, South Korea

RECRUITING

Related 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.

  PMID: 22161917 BACKGROUND

• 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.

  PMID: 25450009 BACKGROUND

• 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.

  PMID: 25430635 BACKGROUND

• 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.

  PMID: 24151279 BACKGROUND

• 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.

  PMID: 28002321 BACKGROUND

• 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.

  PMID: 28153031 BACKGROUND

• 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.

  PMID: 28176599 BACKGROUND

• 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.

  PMID: 21512813 BACKGROUND

• 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. doi: 10.1016/s0049-3848(97)00004-2.

  PMID: 9058494 BACKGROUND

• Blanie 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.

  PMID: 23195143 BACKGROUND

• Reikeras 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.

  PMID: 19067121 BACKGROUND

• Pilbrant A, Schannong M, Vessman J. Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol. 1981;20(1):65-72. doi: 10.1007/BF00554669.

  PMID: 7308275 BACKGROUND

• Nielsen CS, Jans O, Orsnes 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.

  PMID: 27194493 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee; Hemorrhage

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Seung-Baik Kang, MD, PhD

  SMG-SNU Boramae Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seung-Baik Kang, MD, PhD

CONTACT

+82-870-3931; ossbkang@gmail.com

Chan Yoon, MD

CONTACT

+82-870-2316; yoon.chan.alex@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 12, 2017
• Study Start: July 10, 2017
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: January 8, 2019

Record last verified: 2019-01

Locations

KR (1)