Clinical trial NCT02569658
Conditions: Blood Loss Anatomic Total Shoulder Arthroplasty Reverse Total Shoulder Arthroplasty Transfusion Tranexamic Acid
Sponsor: Rush University Medical Center
Start date: 2015-09-01; Completion date: 2017-04-01
Enrollment: 110 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To compare intravenous Tranexamic Acid (TXA) versus normal saline placebo to determine whether or not TXA administration reduces blood loss, decrease in hemoglobin, and rate of transfusions following anatomic and reverse total shoulder arthroplasty (TSA) surgeries.

Detailed description:
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. Transfusion rates have been reported to range from 2.4% to 9.5% in recent studies, with rates over 30% for revision cases. 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. 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. Moreover, the literature demonstrates no increased rate of thromboembolic or other complications associated with TXA administration for hip and knee arthroplasty.

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.

Purpose of the study is to compare intravenous Tranexamic Acid (TXA) versus normal saline placebo to determine whether or not TXA administration reduces blood loss, decrease in hemoglobin, and rate of transfusions following anatomic and reverse total shoulder arthroplasty (TSA) surgeries. With the hypothesis that intravenous TXA will reduce blood loss following TSA.

Arms: arm 1: Group will be administered 1 gram tranexamic acid IV bolus (10 ml solution) 10 minutes prior to incision. arm 2: Group will be administered 10 ml normal saline placebo IV bolus 10 minutes prior to incision
Interventions: intervention 1: Tranexamic Acid intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
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. 
 

ICF_001.pdf: 
Protocol Title: 
NCT02569658 
Date:   March 16, 2015 
Intravenous Tranexamic Acid in Total Shoulder Arthroplasty and Reverse Total 
Shoulder Arthroplasty


Template Version Date: 2/7/2012 
Consent Version Date: 3/16/2015 
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Investigator: Anthony A. Romeo, MD; Gregory P. Nicholson, MD 
Contact Information: 1611 W. Harrison St. Suite 300, Chicago, IL 60612  (312) 432-2468   
Title of Study: Intravenous Tranexamic Acid in Total Shoulder Arthroplasty 
and Reverse Total Shoulder Arthroplasty 
Sponsor: Department of Orthopaedics 
 
 
 
Subject Information Sheet and Consent Form 
 
Introduction 
You are invited to volunteer to take part in this research study.  Before you decide, it is important 
for you to understand why the research is being done and what it will involve.  Please take the 
time to read the following information carefully, as it may contain words you do not understand.  
You may wish to discuss it with your doctor, family, and/or friends.  If there is anything that you 
do not understand or you would like more information, please ask questions and the study doctor 
or study staff will try their best to answer them. Once the study has been explained and you have 
had all your questions answered to your satisfaction, you will be asked to sign this form if you 
wish to participate. 
 
You do not have to take part in this study.  If you agree to take part, you will be asked to sign 
this form.  Your signature means that you have read or had this form read to you and you have 
had all your questions answered by the study doctor or study staff.  Before you have anything 
done for this study, you must sign this form.  A copy of this signed subject information sheet and 
consent form will be given to you.  You will be free to withdraw from this study at any time you 
choose without giving a reason.  This will not affect any future care you will receive.  No 
promises can be made about the outcome of this as far as your current condition, either positive 
or negative.  People who agree to be a part of a research study are called “subjects” instead of 
“patients”. 
 
Why are you invited to participate in this study? 
You are being asked to take part in this study because you are undergoing a total shoulder 
replacement or reverse total shoulder replacement.  
 
What is the purpose of this study? 
The purpose of this study is to compare the use of intravenous (IV, by vein) tranexamic acid 
versus IV saline placebo(A matching salt solution that contains no active ingredients)in subjects 
undergoing total shoulder replacement and reverse total shoulder replacement. Tranexamic acid 
is currently approved by the Food and Drug Administration (FDA) for use in preventing bleeding 
during dental procedures in hemophilia (a bleeding disorder) patients, and in women with heavy 
menstrual bleeding. Tranexamic acid is also commonly used at different hospitals around the 
United States and Europe, including at Rush University Medical Center, to reduce blood loss and 
transfusions (administration of blood products) in trauma victims and patients undergoing knee 
and hip replacements. Tranexamic acid has not been studied in shoulder replacement, so the 
purpose of this study is to see if it reduces blood loss and transfusions in shoulder replacement 
patients. 


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How many people are expected to take part in the study? 
300 subjects are expected to be enrolled in this study at Rush University Medical Center. 
 
What will you be asked to do? 
You will be asked to agree to participate in a study to determine if IV tranexamic acid is more 
effective than placebo at reducing blood loss following total shoulder replacement or reverse 
total shoulder replacement. If you agree to participate you will be randomly assigned to one of 
the two groups being tested (IV tranexamic acid or IV saline placebo). You have a 50/50 chance 
of being assigned to either group, similar to a coin toss. Your care will not differ, except for the 
use of a single dose of IV tranexamic acid or IV saline placebo in the operating room 10 minutes 
prior to your surgery. 
 
How long will you be in the study? 
You will be in the study for the time you are in the hospital during and after your surgery. 
 
You may be removed from this study without your consent. Some possible reasons may include 
the study doctor decides that continued participation in the study will be harmful to you, you will 
need a treatment not allowed on the study, your disease becomes worse, you are unable to take 
the treatment as indicated, or the study is canceled. 
 
What are the possible risks of the study? 
Tranexamic acid is routinely used every day in both primary and revision knee and hip 
replacement surgeries. Although it has not been studied in shoulder replacement patients, 
we anticipate similar effectiveness in reducing blood loss from surgery without increased risk of 
complications. We will be collecting information regarding blood loss during surgery. The risk 
of symptomatic blood loss during surgery is low and participation in this study will not impact 
your care during surgery. There may be a risk of gastrointestinal symptoms such as nausea, 
vomiting or diarrhea as well as risk of hypotension (low blood pressure), dizziness, headache, 
blurred vision, and skin rash. There is also a risk of a blood clot, possibly causing difficulty 
breathing, or swollen ankle and pain in the calf or thigh. The risk of a blood clot is higher if you 
are using hormonal birth control (such as birth control pills), are obese or a smoker. However, 
most studies in orthopedic surgery report no side effects with tranexamic acid use. 
 
There is the potential for breach of confidentiality and/or privacy. Below is a description of the 
procedure for maintaining confidentiality. 
 
Are there benefits to taking part in the study? 
There may be no direct benefit to you for participating in this study. 
 
What other options are there? 
The only alternative to participating in this study is not to participate. You do not need to 
participate in this study to receive your shoulder replacement treatment. 
 
What about confidentiality of your information? 
Records of participation in this research study will be maintained and kept confidential as 
required by law. 
  
 


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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. 
 
A description of this study will be available on http://www.CLINICALTRIALS.gov, as required 
by U.S. law. This Website will not include information that can identify you. At most, the web 
site will include a summary of the results. You can search this website at anytime. 
 
In order to conduct the study, the study doctor, Anthony Romeo, MD or Gregory Nicholson, 
MD will use and share personal health information about you.  This includes information already 
in your medical record, as well as information created or collected during the study.  Examples 
of the information that may be shared include your medical history, physical exam and 
laboratory test results.  The study doctor will use this information about you to complete this 
research. 
 
Confidentiality and disclosure of your personal information is further described in the attachment 
to this form.  The attachment is entitled HIPAA Authorization to Share Personal Health 
Information in Research (2 pages). 
 
Your identity will not be revealed on any report, publication, or at scientific meetings. All study 
materials are stored in secure areas and on secure password protected computers in the secure 
research offices. 
 
The Rush Institutional Review Board (IRB) will have access to your files as they pertain to this 
research study. The IRB is a special committee that reviews new and ongoing human research 
studies to check that the rules and regulations are followed regarding the protection of the rights 
and welfare of human subjects. 
 
What are the costs of your participation in this study? 
All costs that are part of your usual medical care, such as the cost associated with care before, 
during, and after your surgery will be charged to you or your insurance company. You will be 
responsible for all costs that are not paid by your insurance company. The study will be 
responsible for the cost of the tranexamic acid and IV saline placebo. 
 
Will you be compensated or paid? 
You will not receive compensation for study participation. Your participation in this research 
study may contribute to the development of commercial products from which the sponsor, 
company, or others may derive economic benefit.  You will have no rights to any products, 
patents or discoveries arising from this research, and you will receive no economic benefit. 
 
What happens if you experience a research related injury? 
If you experience any injury or illness as a direct result of your participation in this research 
study, immediate treatment will be provided. However, the cost of that treatment will be 
billed to you or your insurance company.  Please check with your insurance company 
regarding coverage. 
 
If you have any medical problems during the study, please contact the study doctor.  He or 


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she will explain your treatment options to you or tell you where you can get treatment.  
 
Rush University Medical Center has no program for financial compensation or other 
forms of compensation for injuries which you may incur as a result of participation in this 
study. 
 
What happens if you need emergency care? 
If you need emergency care while you are participating in this study, it is important that you 
inform emergency personnel of your participation in this study and notify the study doctor as 
soon as possible.  
 
Whom do you call if you have questions or problems? 
Questions are encouraged. If there are any questions about this research study or if you 
experience a research related injury, please contact: Anthony Romeo or Gregory Nicholson, 
1611 W. Harrison St. Suite 300, Chicago IL, 60612; 1-312-432-2452 or 1-312-432-2337. 
Questions about the rights of research subjects may be addressed to the Rush Research & 
Clinical Trials Administration Office at 1-800-876-0772. 
 
By signing below, you are consenting to participate in this research study.  You have read the 
information given or someone has read it to you. You have had the opportunity to ask questions, 
which have been answered satisfactorily to you by the study staff. You do not waive any of your 
legal rights by signing this consent form.  
 
 
SIGNATURE BY THE SUBJECT: 
 
 
 
 
 
 
 
Name of Subject 
Signature of Subject 
Date of Signature 
 
 
 
SIGNATURE BY THE WITNESS: 
I observed the signing of this consent document. 
 
 
 
 
 
Signature of Witness 
Date of Signature 
 
 
SIGNATURE BY THE INVESTIGATOR/INDIVIDUAL OBTAINING CONSENT: 
I attest that all the elements of informed consent described in this document have been discussed 
fully in non-technical terms with the subject.  I further attest that all questions asked by the 
subject were answered to the best of my knowledge.   
 
 
 
 
 
Signature of Individual Obtaining Consent 
Date of Signature 
 
 
 
 
 
Signature of the Principal Investigator 
Date of Signature