Clinical trial NCT02453802: Comparison of Topical and Infusion Tranexamic Acid After Total Knee Arthroplasty
Official title: Comparison of Topical and Infusion Tranexamic Acid on Blood Loss and Risk of Deep Vein Thrombosis After Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Osteoarthritis, Knee
Keywords: Tranexamic Acid
Total Knee Arthroplasty
Rivaroxaban
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2015-05-27
Enrollment: 90
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality
timeFrame: within 15 days after surgery (2 days after the last dose of rivaroxaban )
measure: Incidence of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings
timeFrame: within 15 days after surgery (2 days after the last dose of rivaroxaban )
Secondary outcomes:
measure: Incidence of major venous thromboembolism
timeFrame: within 15 days after surgery (2 days after the last dose of rivaroxaban )
measure: Secondary safety outcome was composite of any non-major bleeding and all wound complications after operation
timeFrame: within 15 days after surgery (2 days after the last dose of rivaroxaban )
measure: Incidence of wound complications after surgery
timeFrame: within 30 days of the procedure
measure: Total blood loss after surgery
timeFrame: From the operation to the postoperative day 4
Other outcomes:
measure: Incidence of venographic positive deep-vein thrombosis (any, proximal, distal)
timeFrame: on the second day after last dose of rivaroxaban (postoperative day 15)
measure: Incidence of positive finding of pulmonary embolism by computed tomography
timeFrame: on the second day after last dose of rivaroxaban (postoperative day 15)
Locations:
city: Koahsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Jun-Wen Wang, MD
role: STUDY_CHAIR
References:
citation: Gomez-Barrena E, Ortega-Andreu M, Padilla-Eguiluz NG, Perez-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.
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.
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.
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.
citation: 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.
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.
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.
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.
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.
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. doi: 10.2106/JBJS.K.00521.