Clinical trial NCT02650856
Conditions: Osteoarthritis
Keywords: Blood loss Tranexamic acid Platelet rich plasma Total knee arthroplasty
Sponsor: Universidad Autonoma de Nuevo Leon
Start date: 2015-09-01; Completion date: 2017-03-09
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: A dosis of 2 gr of tranexamic acid (1000mg/10ml X-GEN pharmaceuticals inc.) diluted in 80ml of physiologic solution and will be divided in two applications.

First application: 40ml 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 40ml of solution previously prepared is applied after placing the final TKR components (femoral, tibial and patellar), over the surgical site and leaving it without draining it by suction. arm 2: A final volumen of 16 ml of platelet rich plasma is obtained from the forearm vein of the patient and will be divided in two applications.

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 after placing the final TKR cemented components (femoral, tibial and patellar), over the surgical site and leaving it without draining.
Interventions: intervention 1: Group 1 Tranexamic Acid intervention 2: Group 2 Platelet rich plasma
Intervention descriptions: intervention 1: 2 gr of tranexamic acid will be applied on the surgical site. intervention 2: 16ml of platelet rich plasma will be applied of the surgical site

Protocol documents:
Prot_SAP_000.pdf: 
 
1
 
1 
Blood Loss Reduction After Total Knee Arthroplasty. Comparison Topical 
2 
Tranexamic Acid vs Platelet Rich Plasma 
3 
 
4 
NCT02650856 
5 
Document Date: October 21, 2019  
6 
Date of Study Closure: April 26 2017 
7 
 
8 
Statistical analysis Plan  
9 
The sample size was calculated using the following characteristics: 90% power and a 
10 
critical p value of 0.05 for a decrease in the transfusion rate of 100% based on a previous 
11 
report and on the assumption that may abate transfusion requirements.[21] This resulted 
12 
in a total of 40 patients. Central tendency and dispersion measures were calculated for 
13 
the numerical variables, and frequencies and percentages were calculated for the 
14 
categorical variables. The Kolmogorov-Smirnov test was performed to test the normal 
15 
distribution of all numerical variables. In the case of parametric numerical variables, 
16 
Student’s t-tests, one-way ANOVA, and multiple comparisons ANOVA were performed for 
17 
related and independent samples. For non-parametric numerical variables, Mann-Whitney 
18 
U, Wilcoxon, and Kruskal Wallis tests were performed. The Bonferroni sequential 
19 
correction test was performed in the post hoc analyses. Statistical significance was set at a 
20 
value of p < 0.05. The SPSS version 20.0 (IBM, Armonk, NY) statistical package for 
21 
Windows 7 was used for the statistical analysis. 
22 
Brief Summary 
23 
 
 
24 
The investigators will include patients who will be schedule for total knee  
25 
arthroplasty with a diagnosis of osteoarthritis. The patients will be divided in two 
26 


 
2
groups. In both groups a verbal and clear detailed information will be given on the 
27 
intraoperative approach. The first group will receive topical tranexamic acid and the 
28 
second group topical platelet rich plasma; both in the surgical site. Both groups will 
29 
be assessed before and after the intervention with laboratory results (hemoglobin, 
30 
hematocrit levels) and drainage drain. 
31 
Detailed Description: 
32 
Total knee replacement (TKR) surgery is one the most common orthopaedic 
33 
procedure in the world. Morbility in perioperative TKR is associated to: blood loss, 
34 
pain, infection, wound complications, stiffness and thrombotic events. Blood loss 
35 
and transfusion have been associated to increased hospital stay, costs, morbility 
36 
and mortality of the patient. Indications for blood transfusions are now limited and it 
37 
is well known that is not a free risk procedure. Complications such as; ABO 
38 
incompatibility, viral transmission, hemolysis, immunosuppression and wound 
39 
infection have been reported. 
40 
Literature reports have reported blood loss in TKR ranging from 300ml to 1 liter, 
41 
and transfusion rate varying from 10-38%. In diminishing hospital cost Moskal J. et 
42 
al reported 53.90% of savings and a 100% reduction in working hours of the 
43 
hospital staff using topical tranexamic acid in TKR. Tranexamic acid is an 
44 
antifibrinolytic agent that acts inhibiting the plasminogen, stabilizing the blood clot; 
45 
it is used to stop surgical or traumatic bleeding like in the CRASH-2 trial, 
46 
demonstrating its efficiency in the polytraumatized patients. Tranexamic acid has 
47 
been used in the last years for blood loss with good results. Due to its systemic 
48 
effects and past medical history of myocardial infarction, stents and previous 
49 
thromboembolic events its intravenous use is limited. In this study the investigators 
50 


 
3
will use topical tranexamic acid and its use has been proven in clinical trials as 
51 
secure strategy por blood loss reduction in TKR, without excluding patients with 
52 
previous thromboembolic events. 
53 
Platelet rich plasma (PRP) is an orthobiologic that has played an important role 
54 
over the past decade in different areas like; spinal fusion, ACL reconstruction, 
55 
osteoarthrosis and tendinopathies. The use of platelet rich plasma (PRP) in 
56 
orthopaedics is overrated and true indications for its use and cost benefit are still 
57 
unclear. Retrospective studies like Pace T et al in 268 patients did not 
58 
demonstrated differences in hospital stay, Postoperative hemoglobin levels, range 
59 
of motion with the use PRP in TKR. Morishita M. Et al in a clinical trial of 40 
60 
patients, using intralesional PRP didn´t show any benefits for blood loss reduction 
61 
in TKR, but good clinical results were observed in clinical scores like KOOS and 
62 
VAS compared to the control group. Other studies have demonstrated the efficacy 
63 
of topical PRP in blood loss reduction in TKR. 
64 
Due to its high platelet concentration and growth factors contained in the alfa 
65 
granules; it is used as an hemostatic, analgesic and antiseptic agent in TKR. 
66 
There is a variety of blood loss prevention strategies for TKR and this strategies 
67 
can be divided in preoperative, intraoperative or postoperative. The aim of this 
68 
study is to compare the use of topical tranexamic acid versus topical platelet rich 
69 
plasma. 
70 
An Insall knee approach, parapatellar medial will be used in all the patients. After 
71 
the final cuts of the femoral, tibial and patellar and before placing the final 
72 
cemented components the experimental intervention of the study will begin. 
73 
Group 1. A dosis of 2 gr of tranexamic acid (1000mg/10mL X-GEN 
74 


 
4
pharmaceuticals inc.) is diluted in 80mL of physiologic solution and will be divided 
75 
in two applications: 
76 
First application: 40mL of the solution previously prepared is applied over the 
77 
surgical site and it will be left for five minutes then drained out completely by 
78 
suction. 
79 
Second application: The rest of 40mL of solution previously prepared is applied 
80 
after placing the final TKR cemented components (femoral, tibial and patellar), over 
81 
the surgical site and leaving it there without draining it by suction. 
82 
Group 2. In the preoperative room with previous premedication, a total of 55cc of 
83 
total venous blood is obtained from the forearm (cubital o basilic veins). The blood 
84 
is carried on 12 steriles tubes using sodium citrate at 3.8% as anticoagulant (BD, 
85 
Vacutainer; Becton, Dickinson and Company, NJ). Blood samples are then 
86 
transported to the Bank of Tissue (Banco de hueso Dr. José E. Gonzalez) where 
87 
by centrifugation at 1800 rpm for 10 minutes (HeraeusMegafuge 1.0R; 
88 
ThermoElectronCorporation) the separation of the 3 layers (White, yellow and red). 
89 
The superior layer rich in plasma will be collected in 50 microliters polypropylene 
90 
tubes (Corning,NY). A final volumen of 16 ml of platelet rich plasma is obtained 
91 
and will transferred to airtight tubes (BD Vacutainer; Becton, Dickinson and 
92 
Company, NJ). The manipulation of the blood samples is made on laminar flow 
93 
cabin biosecurity class II (Logic 3440801; Labconco, KC). The platelet rich plasma 
94 
will be activated with calcium gluconate at 10% (Pisa Farmacéutica, Jalisco, 
95 
México) before using it is placed in the surgical site topically. The PRP simple will 
96 
be divided in two applications, initiating the intervention after the final cuts of the 
97 
TKR components (like the tranexamic acid group). 
98 


 
5
First application: 8 mL of PRP are applied over the surgical site and are left for five 
99 
minutes then drained out completely by suction. 
100 
Second application: The rest of the 8 mL are applied over the surgical site after 
101 
placing the final TKR cemented components (femoral, tibial and patellar), over the 
102 
surgical site and leaving it without draining. 
103 
Then a primary closure of the wound is performed (capsule, fascia, subcutaneous 
104 
tissue and skin) in both groups. A close drainage (Drenovac, NEdren S de R.L. de 
105 
C.V.) is left intraarticular and fixed to the skin. The drainage will be clamped for 2 
106 
hours and removed at the 48 hours of the surgery. Thromboprophylaxis (low 
107 
weight heparin) will be initiated after 6 hours of the end of the surgery. In the 
108 
postoperative follow up, any patient with hemoglobin levels less than 9mg/dl with 
109 
anemic syndrome will be transfused. 
110 
 
111 
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112 
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Frisch NB, Wessell NM, Charters MA, Yu S, Jeffries JJ, Silverton CD. Predictors 
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Pace TB, Foret JL, Palmer MJ, Tanner SL, Snider RG. Intraoperative platelet rich 
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24971180 
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Morishita M, Ishida K, Matsumoto T, Kuroda R, Kurosaka M, Tsumura N. 
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Aggarwal AK, Shashikanth VS, Marwaha N. Platelet-rich plasma prevents blood 
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10.1007/s00264-013-2136-6. Epub 2013 Oct 11.   PubMed ID: 24114251 
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Prospective randomized evaluation of a collagen/thrombin and autologous platelet 
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ID: 22035976 
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Gardner MJ, Demetrakopoulos D, Klepchick PR, Mooar PA. The efficacy of 
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