Combined Topical Tranexamic Acid With Floseal® in Total Knee Arthroplasty

NCT ID: NCT03328832

Last Updated: 2021-08-10

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-12

Study Completion Date

2018-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Our purpose of this study therefore is to conduct a prospective randomized controlled trial to investigate the blood-conservation effect of combined topical application of these two hemostatic agents in different time during surgery and the safety compared with single topical application of TKA in a primary TKA procedure

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Total knee arthroplasty (TKA) is associated with considerable blood loss and increasing needs for allogenic blood transfusion. Tranexamic acid (TXA), an inhibitor of fibrinolysis, was reportedly effective reducing blood loss after standard TKA. Our 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%. There were some reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients.

Besides, thrombin-based hemostatic agents, Floseal®(Baxter, Deerfield, Illinois), have been widely used in surgical procedure. Some recent studies demonstrated that topical use of Floseal® in primary TKA can reduce hemoglobin decline and calculated total blood loss after TKA. But other studies showed Floseal® does not reduce blood loss in TKA procedures.

We believe the topical use of hemostatic agent in patients with high risk of thromboembolism can avoid its systematic effect and decrease its potential perioperative risk of thromboembolic complications (arterial thrombosis, myocardial infarction and pulmonary embolism). Recently, there were some reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients. The blood saving effect of topical application of TXA in primary TKA was similar with systemic administration. The mean total blood loss of topical route of TXA inTKA patients was 940-1295 ml in different reports which was still high for patients with high thromboembolic risks. However, the efficacy and safety of topical use of TXA in TKA patients with history of thromboembolic disease is still unclear. A more effective regimen for bleeding prophylaxis afer primary TKA is necessary.

We believe that combined topical applications of two hemostatic agents of different mechanisms can bring a synergistic effect in blood saving and does not increase the risk of thromboembolic disease after TKA.

Our purpose of this study therefore is to conduct a prospective randomized controlled trial to investigate the blood-conservation effect of combined topical application of these two hemostatic agents in different time during surgery and the safety compared with single topical application of TKA in a primary TKA procedure.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Osteoarthritis, Knee

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Combined topical TXA and Floseal

Floseal® was applied on potential bleeding sites before prosthesis implantation, and intraarticular application of topical tranexamic acid after capsule closure Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.

Group Type ACTIVE_COMPARATOR

Topical tranexamic acid

Intervention Type DRUG

Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule

Floseal®

Intervention Type DRUG

Floseal® (Hemostatic matrix, 10ml, Baxter) was applied on potential bleeding sites: the femoral insertion of the posterior cruciate ligament, the lateral genicular artery after resection of the meniscus, the posterior capsule of the knee joint, the bony surfaces not covered by the implant as well as the pinholes (femur and tibia). The entire content of a 10 mL vial containing the active product (Floseal®) was used. The HM remained in place for 3 minutes and was then gently rinsed from the knee as recommended by the manufacturer (Baxter)

rivaroxaban (10mg)

Intervention Type DRUG

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

Topical TXA alone

Intraarticular application of topical tranexamic acid after capsule closure Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.

Group Type ACTIVE_COMPARATOR

Topical tranexamic acid

Intervention Type DRUG

Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule

rivaroxaban (10mg)

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Topical tranexamic acid

Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule

Intervention Type DRUG

Floseal®

Floseal® (Hemostatic matrix, 10ml, Baxter) was applied on potential bleeding sites: the femoral insertion of the posterior cruciate ligament, the lateral genicular artery after resection of the meniscus, the posterior capsule of the knee joint, the bony surfaces not covered by the implant as well as the pinholes (femur and tibia). The entire content of a 10 mL vial containing the active product (Floseal®) was used. The HM remained in place for 3 minutes and was then gently rinsed from the knee as recommended by the manufacturer (Baxter)

Intervention Type DRUG

rivaroxaban (10mg)

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Topical transamine Thrombin-gelatin matrix Xarelto

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Patients who have advanced knee osteoarthritis are scheduled to undergo primary, unilateral elective total knee replacement surgery
2. Age \> 50 years and \< 90 years
3. Failure of medical treatment or rehabilitation.
4. Hemoglobin \> 11g/dl,
5. No use of non-steroid anti-inflammatory agent one week before operation

Exclusion Criteria

1. Preoperative Hemoglobin ≦11 g/dl
2. History of infection or intraarticular fracture of the affective knee
3. Renal function deficiency (GFR \<30 ml/min/1.73m2)which is relative contraindicated for chemical venous thromboembolism
4. Elevated liver enzyme (AST/ALT level are more than twice normal range) , history of liver cirrhosis, impaired liver function(elevated total bilirubin level) and coagulopathy (including long-term use anticoagulant)
5. History of deep vein thrombosis, ischemic heart disease or stroke
6. Contraindications of tranexamic acid, floseal, or rivaroxaban
7. Allergy to tranexamic acid, floseal, rivaroxaban, or the excipients
8. History of heparin-induced thrombocytopenia (HIT)
9. Coagulopathy or bleeding tendency caused by organ dysfunction, such as cirrhosis, bone marrow suppression etc.
10. Patient who have active bleeding disorder, such as intracranial hemorrhage, upper GI bleeding, hematuria.
11. Patients with known allergies to materials of bovine origin
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Chang Gung Memorial Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Wang Jun-Wen

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jun-Wen Wang, MD

Role: STUDY_CHAIR

Chang Gung Memorial Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Taiwan

References

Explore related publications, articles, or registry entries linked to this study.

Bong MR, Patel V, Chang E, Issack PS, Hebert R, Di Cesare PE. Risks associated with blood transfusion after total knee arthroplasty. J Arthroplasty. 2004 Apr;19(3):281-7. doi: 10.1016/j.arth.2003.10.013.

Reference Type BACKGROUND
PMID: 15067638 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9973048 (View on PubMed)

Goodnough LT, Verbrugge D, Marcus RE. The relationship between hematocrit, blood lost, and blood transfused in total knee replacement. Implications for postoperative blood salvage and reinfusion. Am J Knee Surg. 1995 Summer;8(3):83-7.

Reference Type BACKGROUND
PMID: 7552610 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11476309 (View on PubMed)

Alvarez JC, Santiveri FX, Ramos I, Vela E, Puig L, Escolano F. Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Transfusion. 2008 Mar;48(3):519-25. doi: 10.1111/j.1537-2995.2007.01564.x. Epub 2007 Dec 7.

Reference Type BACKGROUND
PMID: 18067499 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3124428 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2149215 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7772427 (View on PubMed)

Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: a prospective, randomised, double-blind study of 86 patients. J Bone Joint Surg Br. 1996 May;78(3):434-40.

Reference Type BACKGROUND
PMID: 8636182 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11011672 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21286886 (View on PubMed)

Graham ID, Alvarez G, Tetroe J, McAuley L, Laupacis A. Factors influencing the adoption of blood alternatives to minimize allogeneic transfusion: the perspective of eight Ontario hospitals. Can J Surg. 2002 Apr;45(2):132-40.

Reference Type BACKGROUND
PMID: 11939657 (View on PubMed)

Nishihara S, Hamada M. Does tranexamic acid alter the risk of thromboembolism after total hip arthroplasty in the absence of routine chemical thromboprophylaxis? Bone Joint J. 2015 Apr;97-B(4):458-62. doi: 10.1302/0301-620X.97B4.34656.

Reference Type BACKGROUND
PMID: 25820882 (View on PubMed)

Xie J, Ma J, Kang P, Zhou Z, Shen B, Yang J, Pei F. Does tranexamic acid alter the risk of thromboembolism following primary total knee arthroplasty with sequential earlier anticoagulation? A large, single center, prospective cohort study of consecutive cases. Thromb Res. 2015 Aug;136(2):234-8. doi: 10.1016/j.thromres.2015.05.014. Epub 2015 May 21.

Reference Type BACKGROUND
PMID: 26026635 (View on PubMed)

Wong J, Abrishami A, El Beheiry H, Mahomed NN, Roderick Davey J, Gandhi R, Syed KA, Muhammad Ovais Hasan S, De Silva Y, Chung F. Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg Am. 2010 Nov 3;92(15):2503-13. doi: 10.2106/JBJS.I.01518.

Reference Type BACKGROUND
PMID: 21048170 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23541868 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24034510 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23886406 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23906869 (View on PubMed)

Gazzeri R, Galarza M, Alfier A. Safety biocompatibility of gelatin hemostatic matrix (Floseal and Surgiflo) in neurosurgical procedures. Surg Technol Int. 2012 Dec;22:49-54.

Reference Type BACKGROUND
PMID: 22915500 (View on PubMed)

Clapp M, Huang JC. Use of FloSeal Sealant in the Surgical Management of Tubal Ectopic Pregnancy. Case Rep Obstet Gynecol. 2013;2013:906825. doi: 10.1155/2013/906825. Epub 2013 May 29.

Reference Type BACKGROUND
PMID: 23819082 (View on PubMed)

Testini M, Marzaioli R, Lissidini G, Lippolis A, Logoluso F, Gurrado A, Lardo D, Poli E, Piccinni G. The effectiveness of FloSeal matrix hemostatic agent in thyroid surgery: a prospective, randomized, control study. Langenbecks Arch Surg. 2009 Sep;394(5):837-42. doi: 10.1007/s00423-009-0497-5. Epub 2009 May 7.

Reference Type BACKGROUND
PMID: 19421770 (View on PubMed)

Di Francesco A, Flamini S, Fiori F, Mastri F. Hemostatic matrix effects on blood loss after total knee arthroplasty: A randomized controlled trial. Indian J Orthop. 2013 Sep;47(5):474-81. doi: 10.4103/0019-5413.118203.

Reference Type BACKGROUND
PMID: 24133307 (View on PubMed)

Suarez JC, Slotkin EM, Alvarez AM, Szubski CR, Barsoum WK, Patel PD. Prospective, randomized trial to evaluate efficacy of a thrombin-based hemostatic agent in total knee arthroplasty. J Arthroplasty. 2014 Oct;29(10):1950-5. doi: 10.1016/j.arth.2014.05.025. Epub 2014 Jun 5.

Reference Type BACKGROUND
PMID: 25015756 (View on PubMed)

Kim HJ, Fraser MR, Kahn B, Lyman S, Figgie MP. The efficacy of a thrombin-based hemostatic agent in unilateral total knee arthroplasty: a randomized controlled trial. J Bone Joint Surg Am. 2012 Jul 3;94(13):1160-5. doi: 10.2106/JBJS.K.00531.

Reference Type BACKGROUND
PMID: 22623075 (View on PubMed)

Helito CP, Gobbi RG, Castrillon LM, Hinkel BB, Pecora JR, Camanho GL. Comparison of Floseal(r) and electrocautery in hemostasis after total knee arthroplasty. Acta Ortop Bras. 2013;21(6):320-2. doi: 10.1590/S1413-78522013000600004.

Reference Type BACKGROUND
PMID: 24453689 (View on PubMed)

Comadoll JL, Comadoll S, Hutchcraft A, Krishnan S, Farrell K, Kreuwel HT, Bechter M. Comparison of hemostatic matrix and standard hemostasis in patients undergoing primary TKA. Orthopedics. 2012 Jun;35(6):e785-93. doi: 10.3928/01477447-20120525-14.

Reference Type BACKGROUND
PMID: 22691647 (View on PubMed)

Bae KC, Cho CH, Lee KJ, Son ES, Lee SW, Lee SJ, Lim KH. Efficacy of intra-articular injection of thrombin-based hemostatic agent in the control of bleeding after primary total knee arthroplasty. Knee Surg Relat Res. 2014 Dec;26(4):236-40. doi: 10.5792/ksrr.2014.26.4.236. Epub 2014 Dec 2.

Reference Type BACKGROUND
PMID: 25505706 (View on PubMed)

Schwab PE, Thienpont E. Use of a haemostatic matrix does not reduce blood loss in minimally invasive total knee arthroplasty. Blood Transfus. 2015 Jul;13(3):435-41. doi: 10.2450/2015.0199-14. Epub 2015 Jan 26.

Reference Type BACKGROUND
PMID: 25761324 (View on PubMed)

Schwab PE, Thienpont E. Use of a haemostatic matrix (Floseal(R)) does not reduce blood loss in minimally invasive total knee arthroplasty performed under continued aspirin. Blood Transfus. 2016 Mar;14(2):134-9. doi: 10.2450/2015.0023-15. Epub 2015 May 29.

Reference Type BACKGROUND
PMID: 26057492 (View on PubMed)

Lin SY, Chen CH, Fu YC, Huang PJ, Chang JK, Huang HT. The efficacy of combined use of intraarticular and intravenous tranexamic acid on reducing blood loss and transfusion rate in total knee arthroplasty. J Arthroplasty. 2015 May;30(5):776-80. doi: 10.1016/j.arth.2014.12.001. Epub 2014 Dec 5.

Reference Type BACKGROUND
PMID: 25534864 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

201601271A0

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Extended Oral Tranexamic Acid After Total Knee Arthroplasty
NCT06618820 ENROLLING_BY_INVITATION PHASE3