The Blood Saving Effect of Tranexamic Acid in Total Knee Arthroplasty With Rivaroxaban as Thromboprophylaxis

NCT02458729 | Completed Phase 4 DMC

• 1 other identifier: NMRPG8B6181
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study was to conduct a prospective, randomized, double-blind study and assess the efficacy of and safety for thromboprophylaxis of rivaroxaban in total knee arthroplasty patients when tranexamic acid is used for bleeding prophylaxis.

Conditions

Osteoarthritis, Knee

Keywords

Tranexamic Acid; Total Knee Arthroplasty; Rivaroxaban

Outcome Measures

Primary Outcomes (2)

• Incidence of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality

  Primary efficacy outcome is the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality

  within 15 days after surgery (2 days after the last dose of rivaroxaban )

• Incidence of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings

  Primary safety outcome is the composite of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings. Major bleeding was defined as bleeding that was fatal, that involved a critical organ, or that required reoperation or clinically overt bleeding outside the surgical site that was associated with a decrease in the hemoglobin level of 2 g or more per deciliter or requiring infusion of 2 or more units of blood

  within 15 days after surgery (2 days after the last dose of rivaroxaban )

Secondary Outcomes (4)

• Incidence of major venous thromboembolism

  within 15 days after surgery (2 days after the last dose of rivaroxaban

• Secondary safety outcome was composite of any non-major bleeding and all wound complications after operation

  within 15 days after surgery (2 days after the last dose of rivaroxaban

• Incidence of wound complications after surgery

  within 30 days of the procedure

• Total blood loss after surgery

  From the operation to the postoperative day 4

Other Outcomes (2)

• Incidence of venographic positive deep-vein thrombosis (any, proximal, distal)

  on the second day after last dose of rivaroxaban (POD 15)

• Incidence of positive finding of pulmonary embolism by computed tomography

  on the second day after last dose of rivaroxaban (POD 15)

Study Arms (3)

Placebo Group

PLACEBO COMPARATOR

Primary total knee replacement with 0.9% normal saline 20ml administration intravenously twice, five minutes before deflation of the tourniquet and 3 hours after operation Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis

Drug: 0.9% Normal Saline (intraoperative); Drug: 0.9% Normal Saline (3 hours after operation); Drug: rivaroxaban (10mg)

One-dose TXA Group

ACTIVE COMPARATOR

Primary total knee replacement with 1 g Tranexamic Acid 5%,5ml/amp administrated intravenously five minutes before deflation of the tourniquet. and then 0.9% normal saline 20ml administration intravenously 3 hours after operation Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis

Drug: Tranexamic Acid 5%,5ml/amp (intraoperative); Drug: 0.9% Normal Saline (3 hours after operation); Drug: rivaroxaban (10mg)

Two-dose TXA Group

ACTIVE COMPARATOR

Primary total knee replacement with 1 g Tranexamic Acid 5%,5ml/amp administrated intravenously twice, five minutes before deflation of the tourniquet and 3 hours after operation Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis

Drug: Tranexamic Acid 5%,5ml/amp (intraoperative); Drug: Tranexamic Acid 5%,5ml/amp (3 hours after operation); Drug: rivaroxaban (10mg)

Interventions

Tranexamic Acid 5%,5ml/amp (intraoperative) DRUG

tranexamic acid 1g administered intravenously five minutes before deflation of the tourniquet

Also known as: Transamine

One-dose TXA Group; Two-dose TXA Group

Tranexamic Acid 5%,5ml/amp (3 hours after operation) DRUG

tranexamic acid 1g administered intravenously 3 hours after operation

Also known as: Transamine

Two-dose TXA Group

0.9% Normal Saline (intraoperative) DRUG

0.9% Normal Saline 20ml administered intravenously five minutes before deflation of the tourniquet

Also known as: 0.9% sodium chloride

Placebo Group

0.9% Normal Saline (3 hours after operation) DRUG

0.9% Normal Saline 20ml administered intravenously 3 hours after operation

Also known as: 0.9% Normal Saline

One-dose TXA Group; Placebo Group

rivaroxaban (10mg) DRUG

Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14

Also known as: Xarelto

One-dose TXA Group; Placebo Group; Two-dose TXA Group

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• End-stage arthritis of the knee
• Failure of medical treatment or rehabilitation
• Hemoglobin \> 10g/dl
• No use of non-steroid anti-inflammatory agent one week before operation

You may not qualify if:

• Preoperative Hemoglobin ≦10 g/dl
• History of infection or intraarticular fracture of the affective knee
• Renal function deficiency (GFR \< 55 ml/min/1.73m2)which is relative contraindicated for venography
• Elevated liver enzyme, history of liver cirrhosis, impaired liver function and coagulopathy (including long-term use anticoagulant)
• History of deep vein thrombosis, ischemic heart disease or stroke

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Kaohsiung Chang Gung Memorial Hospital

Koahsiung, Taiwan, Taiwan

Location

Related Publications (23)

• Petaja J, Myllynen P, Myllyla G, Vahtera E. Fibrinolysis after application of a pneumatic tourniquet. Acta Chir Scand. 1987 Nov-Dec;153(11-12):647-51.

  PMID: 3124428 BACKGROUND

• Kambayashi J, Sakon M, Yokota M, Shiba E, Kawasaki T, Mori T. Activation of coagulation and fibrinolysis during surgery, analyzed by molecular markers. Thromb Res. 1990 Oct 15;60(2):157-67. doi: 10.1016/0049-3848(90)90294-m.

  PMID: 2149215 BACKGROUND

• Hiippala S, Strid L, Wennerstrand M, Arvela V, Mantyla S, Ylinen J, Niemela H. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth. 1995 May;74(5):534-7. doi: 10.1093/bja/74.5.534.

  PMID: 7772427 BACKGROUND

• Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE, Welch RB. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am. 1999 Jan;81(1):2-10. doi: 10.2106/00004623-199901000-00002.

  PMID: 9973048 BACKGROUND

• Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S. Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. J Bone Joint Surg Br. 2001 Jul;83(5):702-5. doi: 10.1302/0301-620x.83b5.11745.

  PMID: 11476309 BACKGROUND

• Prevention of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence). Int Angiol. 1997 Mar;16(1):3-38. No abstract available.

  PMID: 9165356 BACKGROUND

• Clagett GP, Anderson FA Jr, Geerts W, Heit JA, Knudson M, Lieberman JR, Merli GJ, Wheeler HB. Prevention of venous thromboembolism. Chest. 1998 Nov;114(5 Suppl):531S-560S. doi: 10.1378/chest.114.5_supplement.531s. No abstract available.

  PMID: 9822062 BACKGROUND

• Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. doi: 10.1016/S0140-6736(09)60734-0. Epub 2009 May 4.

  PMID: 19411100 BACKGROUND

• Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. doi: 10.1056/NEJMoa076016.

  PMID: 18579812 BACKGROUND

• Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):381S-453S. doi: 10.1378/chest.08-0656.

  PMID: 18574271 BACKGROUND

• Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, Wheeler HB. Prevention of venous thromboembolism. Chest. 2001 Jan;119(1 Suppl):132S-175S. doi: 10.1378/chest.119.1_suppl.132s. No abstract available.

  PMID: 11157647 BACKGROUND

• Jameson SS, Bottle A, Malviya A, Muller SD, Reed MR. The impact of national guidelines for the prophylaxis of venous thromboembolism on the complications of arthroplasty of the lower limb. J Bone Joint Surg Br. 2010 Jan;92(1):123-9. doi: 10.1302/0301-620X.92B1.22751.

  PMID: 20044690 BACKGROUND

• Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2007 Jan;89(1):33-8. doi: 10.2106/JBJS.F.00163.

  PMID: 17200307 BACKGROUND

• Lotke PA. Rivaroxaban for thromboprophylaxis. N Engl J Med. 2008 Nov 13;359(20):2174; author reply 2175-6. No abstract available.

  PMID: 19009675 BACKGROUND

• Jensen CD, Steval A, Partington PF, Reed MR, Muller SD. Return to theatre following total hip and knee replacement, before and after the introduction of rivaroxaban: a retrospective cohort study. J Bone Joint Surg Br. 2011 Jan;93(1):91-5. doi: 10.1302/0301-620X.93B1.24987.

  PMID: 21196550 BACKGROUND

• Ido K, Neo M, Asada Y, Kondo K, Morita T, Sakamoto T, Hayashi R, Kuriyama S. Reduction of blood loss using tranexamic acid in total knee and hip arthroplasties. Arch Orthop Trauma Surg. 2000;120(9):518-20. doi: 10.1007/s004029900132.

  PMID: 11011672 BACKGROUND

• Lin PC, Hsu CH, Chen WS, Wang JW. Does tranexamic acid save blood in minimally invasive total knee arthroplasty? Clin Orthop Relat Res. 2011 Jul;469(7):1995-2002. doi: 10.1007/s11999-011-1789-y. Epub 2011 Feb 1.

  PMID: 21286886 BACKGROUND

• Friedman RJ, Gallus AS, Cushner FD, Fitzgerald G, Anderson FA Jr; Global Orthopaedic Registry Investigators. Physician compliance with guidelines for deep-vein thrombosis prevention in total hip and knee arthroplasty. Curr Med Res Opin. 2008 Jan;24(1):87-97. doi: 10.1185/030079908x242746.

  PMID: 18028586 BACKGROUND

• Warwick D, Dahl OE, Fisher WD; International Surgical Thrombosis Forum. Orthopaedic thromboprophylaxis: limitations of current guidelines. J Bone Joint Surg Br. 2008 Feb;90(2):127-32. doi: 10.1302/0301-620X.90B2.20106.

  PMID: 18256075 BACKGROUND

• Haas SB, Cook S, Beksac B. Minimally invasive total knee replacement through a mini midvastus approach: a comparative study. Clin Orthop Relat Res. 2004 Nov;(428):68-73. doi: 10.1097/01.blo.0000147649.82883.ca.

  PMID: 15534521 BACKGROUND

• Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery. 1962 Feb;51(2):224-32. No abstract available.

  PMID: 21936146 BACKGROUND

• Lin PC, Hsu CH, Huang CC, Chen WS, Wang JW. The blood-saving effect of tranexamic acid in minimally invasive total knee replacement: is an additional pre-operative injection effective? J Bone Joint Surg Br. 2012 Jul;94(7):932-6. doi: 10.1302/0301-620X.94B7.28386.

  PMID: 22733948 BACKGROUND

• Jameson SS, Rymaszewska M, Hui AC, James P, Serrano-Pedraza I, Muller SD. Wound complications following rivaroxaban administration: a multicenter comparison with low-molecular-weight heparins for thromboprophylaxis in lower limb arthroplasty. J Bone Joint Surg Am. 2012 Sep 5;94(17):1554-8. doi: 10.2106/JBJS.K.00521.

  PMID: 22832942 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Tranexamic Acid; Tranylcypromine; Saline Solution; Sodium Chloride; Rivaroxaban

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Propylamines; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Thiophenes; Sulfur Compounds; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jun-Wen Wang, MD

  Chang Gung Memorial Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: May 28, 2015
• First Posted: June 1, 2015
• Study Start: August 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: June 1, 2015

Record last verified: 2015-05

Locations

TW (1)