Investigation of the Blood Sparing Properties of Intravenous Tranexamic Acid With Anatomic and Reverse Total Shoulder Arthroplasty
Phase: NA
Conditions: Blood Loss, Anatomic Total Shoulder Arthroplasty, Reverse Total Shoulder Arthroplasty, Transfusion, Tranexamic Acid
Sponsor: Rush University Medical Center

Protocol Title: 
NCT02569658 
Date:   March 16, 2015 
Intravenous Tranexamic Acid in Total Shoulder Arthroplasty and Reverse Total 
Shoulder Arthroplasty

Tranexamic Acid for the Reduction of Blood Loss in Total Shoulder Arthroplasty 
and Reverse Total Shoulder Arthroplasty 
Principal Investigators: Gregory Nicholson, MD; Anthony Romeo, MD 
Institution: Rush University Medical Center, Midwest Orthopaedics at Rush 
 
Specific Aim: To determine whether Tranexamic Acid (TXA) administration reduces (1) 
blood loss, (2) decrease in hemoglobin, and (3) rate of transfusions following total 
shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA) surgeries via 
a prospective, randomized, double-blinded, placebo-controlled trial. 
 
Hypothesis: Intravenous TXA will reduce blood loss following TSA and RTSA. 
 
Background/Scientific review: 
Anatomic and reverse total shoulder arthroplasty (TSA) is associated with the risk of 
moderate to significant blood loss that can lead to transfusions. Average estimated blood 
loss has been reported in the range of 354 to 361 mL intraoperatively, not accounting for 
additional postoperative blood loss postoperatively in surgical drains.1,2 Transfusion rates 
have been reported to range from 2.4% to 9.5% in recent studies, with rates over 30% for 
revision cases.1-4. Tranexamic acid (TXA) is a synthetic antifibrinolytic agent that is an 
established method of reducing blood loss and transfusion requirement for patients 
undergoing total hip and knee arthroplasty.5-9 TXA can be administered intravenously, 
topically (intraarticularly), or orally, with most available literature addressing intravenous 
and topical administration.  Systematic reviews and meta-analyses of the total hip and 
knee arthroplasty literature demonstrate approximately a 30% decrease in blood loss and 
50% decrease in transfusion rate with topical or intravenous administration of TXA 
compared to placebo.5-9  Moreover, the literature demonstrates no increased rate of 
thromboembolic or other complications associated with TXA administration for hip and 
knee arthroplasty. 5,6 
 
Despite proven efficacy in the hip and knee arthroplasty literature, there have been no 
studies analyzing the ability of TXA to reduce blood loss and transfusion rate following 
TSA and RTSA. 
 
Study Design:   
- Prospective, randomized, double-blinded, placebo-controlled study 
- Two identical, parallel studies will be conducted for primary TSA and RTSA patients. 
 
Inclusion Criteria:   
- Any patient scheduled for a primary anatomic or reverse TSA 
 
Exclusion Criteria:   
- Allergy to TXA 
- Acquired disturbances of color vision 
- Pre-op use of anticoagulant therapy within five days before surgery 
- History of arterial or venous thromboembolic disease; such as DVT, PE, CVA, TIA 
- Pregnancy or breastfeeding 

- Recent MI (within 6 months of surgery) or any placement of stent regardless of time 
since placement  
- Renal impairment 
- Hemophilia 
- Refusal of blood products 
- Any patient undergoing a revision TSA or revision RTSA 
- Patients who decline to participate 
 
Treatment Groups: 
TSA 
1. Intravenous TXA Group (75 TSAs) – 1 gram TXA IV bolus (10 ml solution) 10 
minutes prior to incision 
2. Placebo Group (75 TSAs) –10 ml normal saline placebo IV bolus 10 minutes 
prior to incision 
RTSA 
1. Intravenous TXA Group (75 RTSAs) – 1 gram TXA IV bolus (10 ml solution) 10 
minutes prior to incision 
2. Placebo Group (75 RTSAs) –10 ml normal saline placebo IV bolus 10 minutes 
prior to incision 
 
Surgical Protocol: 
- Surgeons and patients will be blinded to TXA versus placebo and will proceed with 
routine surgical technique for primary TSA and RTSA in all cases. 
- A surgical drain will be used according to attending surgeon preference. 
 
Blood Transfusion Protocol 
- 
Based upon clinical status and in conjunction with our internal medicine 
colleagues 
 
Demographics/Patient Specifics:   
- 
Age 
- 
Sex 
- 
ASA score 
- 
Weight, Height, BMI 
- 
Type of anesthesia 
- 
Indication for surgery: osteoarthritis, post-traumatic arthritis, rheumatoid arthritis, 
rotator cuff arthropathy 
- 
Co-morbidities: heart disease, hypertension, diabetes, use of NSAID, use of 
steroid 
- 
Estimated intra-operative blood loss, Intra-operative fluids (crystalloid, colloid), 
Operative time, Hospitalization days,  
- 
Pre-operative hemoglobin, hematocrit, PT/INR, Pre-operative PTT, Pre-operative 
platelet count 
 
Outcome Measurements:   
Primary 

1. Post-operative blood loss 
 
Secondary 
2. Post-operative Hgb 
3. Post-operative Hematocrit 
4. Number of units transfused 
5. Proportion of patients transfused 
6. Cost comparison – Cost differences resulted from differences in the blood 
transfusion rate, length of hospital stay, and management of complications as well 
as from the cost of the TXA itself 
7. Complications 
a. DVT or PE 
b. Return to the OR within 30 days 
c. Re-admission within 30 days 
d. Superficial infection 
e. Deep infection 
f. Periprosthetic fracture 
g. Cerebrovascular accident or Transient ischemic attack 
h. Dislocation 
 
Risks/Benefits 
 
The use of TXA is standard of care to reduce blood loss and transfusion rate in both 
primary and revision knee and hip arthroplasty surgeries. TXA side effects include of 
nausea, vomiting and/or diarrhea.  
 
The hip and knee arthroplasty literature indicates no increase in complications with TXA 
use. Therefore, the only risk involved is the potential for breach of confidentiality and/or 
privacy. Below is a description of the procedure for maintaining confidentiality. There is 
no direct benefit to the participants in this study, other than the potential decrease in 
blood loss and transfusion rate.  
 
Procedures for Maintaining Confidentiality 
 
A breach of confidentiality and/or privacy is a risk of this study. To prevent this, all 
collected data will be stored electronically in password-protected files to protect patient 
identity and information. All information will be collected and reviewed by the research 
team only. Data will be maintained on a password-protected computer that will be 
accessible only to the study team. No patient identifiers will be maintained in the 
database. 
 
Statistics 
- Sample size: 150 TSA and 150 RTSA for the two parallel studies, randomly assigned to 
TXA and saline placebo. 
- Power analysis RTSA: Using estimated blood loss from a recent paper at Rush,1 (mean 
353 +/- 232mL), power of 80% to detect a 30% reduction in blood loss at 5% 

significance yields a sample size of 58 each for TXA and placebo. To account for 
attrition, we propose a sample size of 75 RTSA receiving TXA and 75 RTSA receiving 
placebo. 
- Power analysis TSA: Using estimated blood loss from a recent paper at Rush,2 (mean 
361 +/- 220mL), power of 80% to detect a 30% reduction in blood loss at 5% 
significance yields a sample size of 55 each for TXA and placebo. To account for 
attrition, we propose a sample size of 75 TSA receiving TXA and 75 TSA receiving 
placebo. 
- Statistical analysis:  Independent sample t-test will be used for continuous variables 
with normal distribution. Non-parametric tests will be used for non-normal data. Fischer 
exact test will be used for categorical outcomes. Significance of 5% will be used. 
 
References 
 
1. 
Saltzman BM, Chalmers PN, Gupta AK, Romeo AA, Nicholson GP. Complication 
rates comparing primary with revision reverse total shoulder arthroplasty. J 
Shoulder Elbow Surg. 2014;0(0). doi:10.1016/j.jse.2014.04.015. 
2. 
Chalmers PN, Gupta AK, Rahman Z, Bruce B, Romeo AA, Nicholson GP. 
Predictors of early complications of total shoulder arthroplasty. J Arthroplasty. 
2014;29(4):856–860. doi:10.1016/j.arth.2013.07.002. 
3. 
Gupta AK, Chalmers PN, Rahman Z, et al. Reverse total shoulder arthroplasty in 
patients of varying body mass index. J Shoulder Elbow Surg. 2014;23(1):35–42. 
doi:10.1016/j.jse.2013.07.043. 
4. 
Shields E, Iannuzzi JC, Thorsness R, Noyes K, Voloshin I. Perioperative 
complications after hemiarthroplasty and total shoulder arthroplasty are equivalent. J 
Shoulder Elbow Surg. 2014;23(10):1449–1453. doi:10.1016/j.jse.2014.01.052. 
5. 
Yang Z-G, Chen W-P, Wu L-D. Effectiveness and safety of tranexamic acid in 
reducing blood loss in total knee arthroplasty: a meta-analysis. J Bone Joint Surg 
Am. 2012;94(13):1153–1159. doi:10.2106/JBJS.K.00873. 
6. 
Gandhi R, Evans HMK, Mahomed SR, Mahomed NN. Tranexamic acid and the 
reduction of blood loss in total knee and hip arthroplasty: a meta-analysis. BMC Res 
Notes. 2013;6(1):184. doi:10.1186/1756-0500-6-184. 
7. 
Alshryda S, Mason J, Sarda P, et al. 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;95(21):1969–1974. 
doi:10.2106/JBJS.L.00908. 
8. 
Alshryda S, Mason J, Vaghela M, et al. Topical (intra-articular) tranexamic acid 
reduces blood loss and transfusion rates following total knee replacement: a 
randomized controlled trial (TRANX-K). J Bone Joint Surg Am. 2013;95(21):1961–
1968. doi:10.2106/JBJS.L.00907. 

9. 
Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the 
reduction of bleeding. Ker K, ed. Cochrane Database Syst Rev. 2013;7:CD010562. 
doi:10.1002/14651858.CD010562.pub2.