Clinical trial NCT02650856: Blood Loss Reduction After Total Knee Arthroplasty. Comparison Topical Tranexamic Acid vs Platelet Rich Plasma
Official title: Blood Loss Reduction After Total Knee Arthroplasty. A Comparison Between Topical Tranexamic Acid and Platelet Rich Plasma: Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis
Keywords: Blood loss
Tranexamic acid
Platelet rich plasma
Total knee arthroplasty
Lead sponsor: Universidad Autonoma de Nuevo Leon
Sponsor class: OTHER
First posted: 2016-01-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators will include patients who will be schedule for total knee arthroplasty with a diagnosis of osteoarthritis. The patients will be divided in two groups. In both groups a verbal and clear detailed information will be given on the intraoperative approach. The first group will receive topical tranexamic acid and the second group topical platelet rich plasma; both in the surgical site. Both groups will be assessed before and after the intervention with laboratory results (hemoglobin, hematocrit levels) and drainage drain.

Detailed description: Total knee replacement (TKR) surgery is one the most common orthopedic procedure in the world. Morbidity in perioperative TKR is associated with: blood loss, pain, infection, wound complications, stiffness, and thrombotic events. Blood loss and transfusion have been associated with an increased hospital stay, costs, morbidity, and mortality. Indications for blood transfusions are now limited and it is well known that is not a free risk procedure. Complications such as; ABO incompatibility, viral transmission, hemolysis, immunosuppression, and wound infection have been reported.

Literature reports have reported blood loss in TKR ranging from 300ml to 1 liter, and transfusion rate varying from 10-38%. In diminishing hospital cost Moskal J. et al. reported 53.90% of savings and a 100% reduction in working hours of the hospital staff using topical tranexamic acid in TKR. Tranexamic acid is an antifibrinolytic agent that acts inhibiting the plasminogen, stabilizing the blood clot; it is used to stop surgical or traumatic bleeding like in the CRASH-2 trial, demonstrating its efficiency in polytraumatized patients. Tranexamic acid has been used in the last years for blood loss with good results. Due to its systemic effects and past medical history of myocardial infarction, stents, and previous thromboembolic events its intravenous use is limited. In this study, the investigators used topical tranexamic acid and its use has been proven in clinical trials as a secure strategy for blood loss reduction in TKR, without excluding patients with previous thromboembolic events.

Platelet-rich plasma (PRP) is an orthobiologic that has played an important role over the past decade in different areas like; spinal fusion, anterior cruciate ligament reconstruction, osteoarthritis, and tendinopathies. The use of PRP in orthopedics is overrated and true indications for its use and cost-benefit are still unclear. Retrospective studies like Pace T et al in 268 patients did not demonstrate differences in-hospital stay, Postoperative hemoglobin levels, and range of motion using PRP in TKR. Morishita M. et al. in a clinical trial of 40 patients, using intralesional PRP didn´t show any benefits for blood loss reduction in TKR, but good clinical results were observed in clinical scores like Knee injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale (VAS) compared to the control group. Other studies have demonstrated the efficacy of topical PRP in blood loss reduction in TKR.

Due to its high platelet concentration and growth factors contained in the alfa granules; it is used as a hemostatic, analgesic, and antiseptic agent in TKR.

There is a variety of blood loss prevention strategies for TKR and these strategies can be divided into preoperative, intraoperative, or postoperative. This study aimed to compare the use of topical tranexamic acid versus topical platelet-rich plasma.

An Insall knee approach, parapatellar medial will be used in all the patients. After the final cuts of the femoral, tibial and patellar and before placing the final cemented components the experimental intervention of the study will begin.

Group 1. A dose of 2 gr of tranexamic acid (1000mg/10 mL X-GEN pharmaceuticals inc.) is diluted in 80 mL of physiologic solution and will be divided into two applications:

First application: 40 mL of the solution previously prepared is applied over the surgical site and it will be left for five minutes then drained out completely by suction.

Second application: The rest of the 40 mL of solution previously prepared is applied after placing the final TKR cemented components (femoral, tibial, and patellar), over the surgical site and leaving it there without draining it by suction.

Group 2. In the preoperative room with previous premedication, a total of 55 mL of total venous blood is obtained from the forearm (cubital o basilic veins). The blood is carried on 12 sterile tubes using sodium citrate at 3.8% (BD, Vacutainer; Becton, Dickinson and Company, NJ). Blood samples are then transported to the Bone and Tissue Bank for centrifugation (1800 rpm for 10 minutes) to separate blood into the 3 layers (White, yellow and red). The superior layer rich in plasma will be collected in 50 microliters polypropylene tubes (Corning, NY). A final volume of 16 ml of platelet-rich plasma is obtained and transferred to airtight tubes (BD Vacutainer; Becton, Dickinson and Company, NJ). The manipulation of the blood samples is made on laminar flow cabin biosecurity class II (Logic 3440801; Labconco, KC). The platelet-rich plasma will be activated with calcium gluconate at 10% (Pisa Farmacéutica, Jalisco, México) before using it is placed in the surgical site topically. The PRP simple will be divided into two applications, initiating the intervention after the final cuts of the TKR components (like the tranexamic acid group).

First application: 8 ml of PRP are applied over the surgical site and are left for five minutes then drained out completely by suction.

Second application: The rest of the 8 ml are applied over the surgical site after placing the final TKR cemented components (femoral, tibial, and patellar), over the surgical site and leaving it without draining.

Then a primary closure of the wound is performed (capsule, fascia, subcutaneous tissue, and skin) in both groups. Close drainage (Drenovac, NEdren S de R.L. de C.V.) is left intraarticular and fixed to the skin. The drainage will be clamped for 2 hours and removed at the 48 hours of the surgery. Thromboprophylaxis (low weight heparin) will be initiated after 6 hours of the end of the surgery. In the postoperative follow-up, any patient with hemoglobin levels less than 9mg/dL with the anemic syndrome will be transfused.

Eligibility criteria: Inclusion Criteria:

1. Age \>18 years
2. Patient candidates for primary total knee replacement
3. Patients willing to participate in the study and sign de inform consent

Exclusion Criteria:

1. Patients with previous history of thromboembolic event in the last 6 months
2. Patients candidates for revision total knee replacement
3. Patients candidates for tumoral total knee replacement
4. Patients candidates for bilateral total knee replacement
5. Patient with cognitive deficit
6. Previous history of coagulopathy

Primary outcomes:
measure: Therapeutic Effect on Hemoglobin Level
timeFrame: up to 3rd day post operative (Baseline, 24, 48 and 72hrs)
Secondary outcomes:
measure: Therapeutic Effect on Hematocrit Level
timeFrame: up to 3rd day post operative (Baseline, 24, 48 and 72hrs)
measure: Therapeutic Effect on Drainage Quantification
timeFrame: up to 2nd day post operative (24 and 48 hrs)
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Facultad de Medicina UANL
state: Nuevo Leon
Study officials:
affiliation: Hospital Universitario, Universidad Autonoma de Nuevo Leon
name: Felix Vilchez, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levine BR, Haughom B, Strong B, Hellman M, Frank RM. Blood management strategies for total knee arthroplasty. J Am Acad Orthop Surg. 2014 Jun;22(6):361-71. doi: 10.5435/JAAOS-22-06-361.
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: Frisch NB, Wessell NM, Charters MA, Yu S, Jeffries JJ, Silverton CD. Predictors and complications of blood transfusion in total hip and knee arthroplasty. J Arthroplasty. 2014 Sep;29(9 Suppl):189-92. doi: 10.1016/j.arth.2014.03.048. Epub 2014 May 24.
citation: Moskal JT, Harris RN, Capps SG. Transfusion cost savings with tranexamic acid in primary total knee arthroplasty from 2009 to 2012. J Arthroplasty. 2015 Mar;30(3):365-8. doi: 10.1016/j.arth.2014.10.008. Epub 2014 Oct 12.
citation: CRASH-2 trial collaborators; Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.
citation: Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E, Ayeni OR, Bhandari M. Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am. 2012 Feb 15;94(4):298-307. doi: 10.2106/JBJS.K.00154.
citation: Patel JN, Spanyer JM, Smith LS, Huang J, Yakkanti MR, Malkani AL. Comparison of intravenous versus topical tranexamic acid in total knee arthroplasty: a prospective randomized study. J Arthroplasty. 2014 Aug;29(8):1528-31. doi: 10.1016/j.arth.2014.03.011. Epub 2014 Mar 21.
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: 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: Sarzaeem MM, Razi M, Kazemian G, Moghaddam ME, Rasi AM, Karimi M. Comparing efficacy of three methods of tranexamic acid administration in reducing hemoglobin drop following total knee arthroplasty. J Arthroplasty. 2014 Aug;29(8):1521-4. doi: 10.1016/j.arth.2014.02.031. Epub 2014 Mar 6.
citation: Alshryda S, Mason J, Sarda P, Nargol A, Cooke N, Ahmad H, Tang S, Logishetty R, Vaghela M, McPartlin L, Hungin AP. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (TRANX-H). J Bone Joint Surg Am. 2013 Nov 6;95(21):1969-74. doi: 10.2106/JBJS.L.00908.
citation: Pace TB, Foret JL, Palmer MJ, Tanner SL, Snider RG. Intraoperative platelet rich plasma usage in total knee arthroplasty: does it help? ISRN Orthop. 2013 Jul 28;2013:740173. doi: 10.1155/2013/740173. eCollection 2013.
citation: Morishita M, Ishida K, Matsumoto T, Kuroda R, Kurosaka M, Tsumura N. Intraoperative platelet-rich plasma does not improve outcomes of total knee arthroplasty. J Arthroplasty. 2014 Dec;29(12):2337-41. doi: 10.1016/j.arth.2014.04.007. Epub 2014 Apr 13.
citation: Aggarwal AK, Shashikanth VS, Marwaha N. Platelet-rich plasma prevents blood loss and pain and enhances early functional outcome after total knee arthroplasty: a prospective randomised controlled study. Int Orthop. 2014 Feb;38(2):387-95. doi: 10.1007/s00264-013-2136-6. Epub 2013 Oct 11.
citation: Bloomfield MR, Klika AK, Molloy RM, Froimson MI, Krebs VE, Barsoum WK. Prospective randomized evaluation of a collagen/thrombin and autologous platelet hemostatic agent during total knee arthroplasty. J Arthroplasty. 2012 May;27(5):695-702. doi: 10.1016/j.arth.2011.09.014. Epub 2011 Oct 27.
citation: Gardner MJ, Demetrakopoulos D, Klepchick PR, Mooar PA. The efficacy of autologous platelet gel in pain control and blood loss in total knee arthroplasty. An analysis of the haemoglobin, narcotic requirement and range of motion. Int Orthop. 2007 Jun;31(3):309-13. doi: 10.1007/s00264-006-0174-z. Epub 2006 Jul 1.