Comparison of Topical and Infusion Tranexamic Acid After Total Knee Arthroplasty

Osteoarthritis, Knee Clinical Trial

Official title:

Comparison of Topical and Infusion Tranexamic Acid on Blood Loss and Risk of Deep Vein Thrombosis After Total Knee Arthroplasty

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02453802
• Other study ID #: CMRPG8D1051
• Status: Not yet recruiting
• Phase: Phase 4
• First received: May 4, 2015
• Last updated: May 26, 2015
• Start date: June 2015
• Est. completion date: May 2016

Study information

• Verified date: May 2015
• Source: Chang Gung Memorial Hospital
• Contact: Jun-Wen Wang, MD
• Phone: 886-7-7317123
• Email: wangjw[@]adm.cgmh.org.tw
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of the study, therefore, is to conduct a prospective randomized controlled trial to investigate the blood-conservation effect of TXA in different TKA patients groups with rivaroxaban for VTE prophylaxis, first group by topical application, second group by infusion and a third group of placebo and observe whether there is difference in the occurrence of venous thromboembolism in those patient groups by venographic study

Description:

Investigators previous experiences in minimally invasive (MIS) TKA showed that intraoperative infusion of TXA reduced 45% of postoperative blood loss and needs for transfusion from 20% to 4%. However, most of the orthopedic surgeons still hesitate to use TXA systemically in TKAs especially in high risk patients with a potential increase in thromboembolic events following surgery.

Because of this concern, recently, there were few reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients. However, most of the reports compared the topical TXA with placebo in TKA patients, not with intravenous TXA. Recently, Georgiadis et al. conducted a double-blind, randomized controlled clinical trial are demonstrated similar transfusion rate and perioperative blood loss between topical administration and intravenous injection of TXA in TKA patients. There were no significant safety differences between the two groups. Low-molecular weight heparin (LMWH) was used for thromboembolism prophylaxis in that study.

Recently, chemical VTE prophylaxis such as rivaroxaban has been approved as a standard care after TKA because of its superior convenience and efficacy on VTE prophylaxis to LMWH in TKAs. However, because of direct blockage of the formation of thrombin from prothrombin by rivaroxaban, an increased postoperative bleeding has been reported. There have been little studies investigating the blood-conservation effect of TXA on TKA patients either by infusion or by topical application when rivaroxaban used as VTE prophylaxis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Osteoarthritis, Knee

Intervention

Drug:
• Tranexamic Acid 5%,5ml/amp
Intraarticular application of tranexamic acid 3g (60ml) in 100 ml normal saline into knee joint after closure of the joint capsule
• Tranexamic Acid 5%,5ml/amp
IV TXA group: Primary total knee replacement with 1 g tranexamic acid administrated intravenously before deflection of the tourniquet
• rivaroxaban (10mg)
Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14.
• 0.9% Normal Saline
Primary total knee replacement with intravenous normal saline (20 ml) administration before deflation of the tourniquet
• 0.9% Normal Saline
Topical 160 ml normal saline application after closure of joint capsule.

Locations

Country	Name	City	State
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Koahsiung

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (10)

Chimento GF, Huff T, Ochsner JL Jr, Meyer M, Brandner L, Babin S. An evaluation of the use of topical tranexamic acid in total knee arthroplasty. J Arthroplasty. 2013 Sep;28(8 Suppl):74-7. doi: 10.1016/j.arth.2013.06.037. — View Citation

Georgiadis AG, Muh SJ, Silverton CD, Weir RM, Laker MW. A prospective double-blind placebo controlled trial of topical tranexamic acid in total knee arthroplasty. J Arthroplasty. 2013 Sep;28(8 Suppl):78-82. doi: 10.1016/j.arth.2013.03.038. Epub 2013 Jul 29. — View Citation

Gomez-Barrena E, Ortega-Andreu M, Padilla-Eguiluz NG, Pérez-Chrzanowska H, Figueredo-Zalve R. Topical intra-articular compared with intravenous tranexamic acid to reduce blood loss in primary total knee replacement: a double-blind, randomized, controlled, noninferiority clinical trial. J Bone Joint Surg Am. 2014 Dec 3;96(23):1937-44. doi: 10.2106/JBJS.N.00060. — View Citation

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. — View Citation

Konig G, Hamlin BR, Waters JH. Topical tranexamic acid reduces blood loss and transfusion rates in total hip and total knee arthroplasty. J Arthroplasty. 2013 Oct;28(9):1473-6. doi: 10.1016/j.arth.2013.06.011. Epub 2013 Jul 23. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Wind TC, Barfield WR, Moskal JT. The effect of tranexamic acid on blood loss and transfusion rate in primary total knee arthroplasty. J Arthroplasty. 2013 Aug;28(7):1080-3. doi: 10.1016/j.arth.2012.11.016. Epub 2013 Mar 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of venographic positive deep-vein thrombosis (any, proximal, distal)		on the second day after last dose of rivaroxaban (postoperative day 15)	No
Other	Incidence of positive finding of pulmonary embolism by computed tomography		on the second day after last dose of rivaroxaban (postoperative day 15)	No
Primary	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 )	No
Primary	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 )	Yes
Secondary	Incidence of major venous thromboembolism	the secondary efficacy outcomes include major venous thromboemolism defined as the composite of proximal deep-vein thrombosis, non-fatal pulmonary embolism, and VTE related death	within 15 days after surgery (2 days after the last dose of rivaroxaban )	No
Secondary	Secondary safety outcome was composite of any non-major bleeding and all wound complications after operation	non-major bleeding including hemorrhagic wound complications (excessive wound hematoma or bleeding at the surgical site	within 15 days after surgery (2 days after the last dose of rivaroxaban )	Yes
Secondary	Incidence of wound complications after surgery	composite of hematoma, superficial wound infection, and deep infection requiring return to surgery	within 30 days of the procedure	Yes
Secondary	Total blood loss after surgery	Total blood loss was calculated according to Nadler et al., which used maximum postoperative reduction of the Hb level adjust for weight and height of the patient. The formula is as follows, Total blood loss = (Total blood volume x [change in Hb level / preoperative Hb level])x1000+volume transfused.	From the operation to the postoperative day 4	Yes