Clinical trial NCT04560010
Conditions: Total Shoulder Athroplasty
Sponsor: NYU Langone Health
Start date: 2020-10-06; Completion date: 2023-03-11
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, single-blind, single-center study comparing calculated total blood loss, surgical drain output and hematoma formation in anticoagulated patients who receive 2 doses of Tranexamic Acid (TXA) versus control group undergoing anatomical and reverse total shoulder arthroplasty (TSA). Patients will be randomized to either receive 2 doses of IV TXA, first dose prior to surgical incision and second dose given 3 hours later or to the control group, where no TXA will be administered.

Detailed description:

Arms: arm 1: Subjects scheduled to undergo TSA (anatomic and reverse) will receive TXA before surgical incision and 3 hours later. arm 2: Subjects scheduled to undergo TSA (anatomic and reverse) will receive no TXA.
Interventions: intervention 1: Tranexamic Acid Injection (TXA)
Intervention descriptions: intervention 1: Injection of 1 gram of IV TXA before surgical plus 1 gram of IV TXA three hours later

Protocol documents:
Prot_SAP_001.pdf: 
 
 
Page 1 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
The picture can't be displayed.
 
 
 
 
The Effect of Tranexamic Acid on Calculated Total Blood Loss in 
Anticoagulated patients undergoing Total Shoulder Arthroplasty 
 
This is a randomized, single-blind, single-center study comparing calculated total blood loss, surgical drain 
output and hematoma formation in anticoagulated patients who receive 2 doses of  Tranexamic Acid (TXA) 
versus control group undergoing anatomical and reverse total shoulder arthroplasty. Patients will be 
randomized to either receive  2 doses of IV TXA, first dose prior to surgical incision and second dose given 
3 hours later or to the control group, where no TXA will be administered.   
 
Principal Investigator: 
 
Arthur C. Hertling, MD, MBA 
Department of Anesthesiology, Perioperative Care and Pain Med 
 
NYU Langone Health  
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
 
Arthur.Hertling@nyulangone.org 
O: (212) 598-6085  
 
Additional Investigators: 
 
 
 
Young Kwon, MD, PhD 
Department of Orthopedic Surgery 
 
NYU Langone Health  
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
Young.Kwon@nyulangone.org 
 
O:(646) 501-7170  
NYULMC Study Number: 
s20-00803  
Study Product: 
 
ClinicalTrials.gov Number       
 
Initial version: 08/21/2020 
Amended:  
04.21.2022 
Amended:


Study number: S20-00803 
 
Page 2 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable 
US government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred 
to as “ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS 
regulations. The Principal Investigator will assure that no deviation from, or changes to the protocol will 
take place without prior agreement from the sponsor and documented approval from the Institutional 
Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants. 
All personnel involved in the conduct of this study have completed Human Subjects Protection Training. 
 
 


Study number: S20-00803 
 
Page 3 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Table of Contents 
 
STATEMENT OF COMPLIANCE ........................................................................................................ 2 
LIST OF ABBREVIATIONS ................................................................................................................... 5 
PROTOCOL SUMMARY ........................................................................................................................ 6 
1 
KEY ROLES ..................................................................................................................................... 7 
2 
BACKGROUND AND SPECIFIC AIMS ...................................................................................... 7 
2.1 
SPECIFIC AIMS ........................................................................................................................... 8 
2.1 
STATISTICAL HYPOTHESES ........................................................................................................ 8 
2.2 
OBJECTIVES AND PURPOSE ........................................................................................................ 9 
3 
STUDY DESIGN AND ENDPOINTS .......................................................................................... 10 
3.1 
DESCRIPTION OF STUDY DESIGN ............................................................................................. 10 
3.2 
SCHEMATIC OF STUDY DESIGN ................................................................................................ 11 
4 
STUDY ENROLLMENT AND WITHDRAWAL ....................................................................... 12 
4.1 
INCLUSION CRITERIA ............................................................................................................... 12 
4.2 
EXCLUSION CRITERIA .............................................................................................................. 12 
4.3 
VULNERABLE SUBJECTS .......................................................................................................... 12 
4.4 
RECRUITMENT AND CONSENT ................................................................................................. 12 
4.5 
DURATION OF STUDY PARTICIPATION ..................................................................................... 13 
4.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES ........................................................................ 13 
4.7 
PARTICIPANT WITHDRAWAL OR TERMINATION ...................................................................... 13 
4.8 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .......................................................... 13 
5 
RISKS AND BENEFITS ................................................................................................................ 14 
5.1 
POTENTIAL RISKS .................................................................................................................... 14 
5.2 
POTENTIAL BENEFITS .............................................................................................................. 14 
6 
STATISTICAL ANALYSIS .......................................................................................................... 15 
6.1 
GENERAL APPROACH ............................................................................................................... 16 
6.2 
ANALYSIS OF ENDPOINTS ........................................................................................................ 16 
6.2.1 
Baseline Descriptive Statistics ............................................................................................ 16 
6.3 
SAMPLE SIZE ............................................................................................................................ 16 
6.4 
ENROLLMENT/RANDOMIZATION/MASKING PROCEDURES ...................................................... 17 
6.5 
BREAKING THE STUDY BLIND/PARTICIPANT CODE................................................................. 17 
7 
ASSESSMENT OF SAFETY ........................................................................................................ 17 
7.1 
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) ................................................................. 17 
7.2 
CLASSIFICATION OF AN ADVERSE EVENT................................................................................ 18 
7.2.1 
Severity of Event .................................................................................................................. 18 
7.2.2 
Relationship to Study Agent................................................................................................. 18 
7.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ......................... 19 
7.4 
SAFETY OVERSIGHT ................................................................................................................. 19 
8 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................... 20 
9 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................... 21 


Study number: S20-00803 
 
Page 4 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
9.1 
ETHICAL STANDARD ................................................................................................................ 21 
9.2 
INSTITUTIONAL REVIEW BOARD ............................................................................................. 21 
9.3 
PARTICIPANT AND DATA CONFIDENTIALITY ........................................................................... 21 
10 
DATA HANDLING AND RECORD KEEPING ........................................................................ 21 
10.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES ................................................... 21 
10.2 
STUDY RECORDS RETENTION .................................................................................................. 22 
10.3 
PROTOCOL DEVIATIONS ........................................................................................................... 22 
10.4 
PUBLICATION AND DATA SHARING POLICY ............................................................................ 22 
11 
STUDY FINANCES ....................................................................................................................... 23 
11.1 
FUNDING SOURCE .................................................................................................................... 23 
11.2 
COSTS TO THE PARTICIPANT .................................................................................................... 23 
11.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS .................................................................... 23 
12 
CONFLICT OF INTEREST POLICY ......................................................................................... 23 
13 
REFERENCES ............................................................................................................................... 24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study number: S20-00803 
 
Page 5 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
List of Abbreviations 
 
AE 
Adverse event 
ANOVA 
Analysis of variance; a linear model   
ASA 
American Society of Anesthesiologist Score 
CI 
Confidence interval 
DVT 
Deep vein thrombosis 
IV 
Intravenous 
MI 
Myocardial Infarction   
NSAID 
Non-steroidal anti-inflammatory drug 
PACU 
Post-Anesthesia Care Unit  
PE 
Pulmonary Embolus 
PO 
Taken orally 
PRN 
Taken as needed 
Q4h 
Taken every four hours 
rTSA  
Reverse Total Shoulder Arthroplasty   
SAE 
Serious adverse event 
SD 
Standard deviation; a parameter that characterizes a population distribution 
SE 
Standard error 
TID 
Taken three times per day 
TSA 
Total Shoulder Arthroplasty 
TXA 
Tranexamic Acid 
VAS 
Visual analog scale 


Study number: S20-00803 
 
Page 6 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Protocol Summary 
Title 
The Effect of Tranexamic Acid in Anticoagulated Patients undergoing Total 
Shoulder Athroplasty 
Short Title 
TXA in Anticoagulated Patients Study  
Brief Summary 
This is a randomized, single-blind, single-center study comparing calculated 
total blood loss, surgical drain output and hematoma formation in 
anticoagulated patients who receive 2 doses of  Tranexamic Acid (TXA) versus 
control group undergoing anatomical and reverse total shoulder arthroplasty. 
Patients will be randomized to either receive  2 doses of IV TXA, first dose 
prior to surgical incision and second dose given 3 hours later or to the control 
group, where no TXA will be administered.  
Objectives 
To compare the effectiveness of IV TXA on reducing calculated total blood 
loss, surgical drain output and hematoma formation in anticoagulated patients 
undergoing anatomic or reverse total shoulder arthroplasty.   
Methodology 
Randomized, single-blind, single-center study  
Endpoints 
 
Primary Endpoints: 
• 
Calculated total blood loss 
• 
Surgical drain output 
  
 
Secondary Endpoints: 
• 
Development of Hematoma (within 14 days after surgery) 
• 
Need for blood transfusion  
• 
Adverse events, DVT, PE, MI( after 48 hours) 
• 
Operative time 
 
Study Duration 
3 years   
Participant Duration 
2 weeks  
Duration of IP 
administration 
Once during surgery 
Population 
82 participants scheduled for Total Shoulder Arthroplasty 
Study Sites 
NYU Langone Orthopedic Hospital (LOH)  
Number of 
participants 
82 participants  
Description of Study 
Agent/Procedure 
Injection of 1 gram of  IV TXA before surgical plus 1 gram of IV TXA three 
hours later 
Reference Therapy 
Reference is No TXA (control)  
Key Procedures 
Injection of Tranexamic Acid   
Statistical Analysis 
Intention-to-treat analysis will be performed with mean, t-tests, within and 
between group ANOVA and linear regression, Wilcoxon’s rank-sum 


Study number: S20-00803 
 
Page 7 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
1 
Key Roles 
 
Principal Investigator:    
 
Arthur C. Hertling, MD, FASA, MBA  
Professor of Anesthesiology 
Department of Anesthesiology, Perioperative care and Pain Medicine 
NYU Langone Orthopedic Hospital 
NYU Langone Health 
301 East 17th street 
New York, NY 10003 
 
Co-Investigators:   
 
Young Kwon, MD, PhD 
Associate Professor of Orthopedic Surgery 
Department of Orthopedic Surgery 
Center for Musculoskeletal Care 
NYU Langone Health 
333 East 38th street 
New York, NY 10016 
2 
Background and Specific Aims  
 
Anatomic total shoulder arthroplasty (TSA) is a surgical procedure where the damaged glenohumeral 
joint is replaced by a metal and plastic prosthesis.  The anatomic TSA has been used to alleviate pain 
caused by a range of medical diseases including but not limited to the following:  arthritic destruction of 
the glenohumeral joint and necrosis of the humeral head with intact rotator cuff.  Reverse total shoulder 
arthroplasty (rTSA) is indicated to treat rotator cuff tear arthropathy. The rTSA is a more technically 
demanding surgical procedure and is thus associated with longer operative time and increased risk for 
blood loss (Kuo).  In rTSA the dead space between the acromion and proximal humerus is increased which 
results more frequently in a hematoma (Box). The average blood loss from rTSA has been documented to 
be more than for the anatomical TSA. Although these findings have been reported in the literature, at our 
institution, rTSA is not associated with longer operative time or higher blood loss. It is actually considered 
less technically demanding than anatomic TSA by our shoulder surgeons. 
 
Oral anticoagulants are commonly used for the primary prevention of thromboembolic events in patients 
with atrial fibrillation and prosthetic heart valves. It is also used for secondary prevention after systemic 
emobolism in pateints with mitral valve disease, mitral valve prolapse, mitral anular calcification, non 
rheumatic mitral regurgitation, and mobile aortic atheromas or aortic plaques larger than 4mm. 
(Schulman). One of the main disadvantages of the use of oral antiocoagulant therapy is the increased risk 
of bleeding after surgical procedures.  Pateints on oral anticoagulants are usually older with multiple 
comorbidities. 
 
Tranexamic acid (TXA) is a synthetic lysine analog that inhibits the conversion of plasmin from 
plasminogen thereby preventing the breakdown of fibrin (McCormack).  This action stabilizes blood clots 
and has been shown to decrease the risk of blood loss for several different types of orthopedic surgeries.  


Study number: S20-00803 
 
Page 8 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
TXA is increasingly used in orthopedic joint reconstructive surgery and has proven to be safe and effective 
in reducing blood loss following total knee arthroplasty (TKA) and total hip arthroplasty (THA) 
(Fillingham, Yang).  More recently, it has been shown to reduce postoperative blood loss following total 
shoulder arthroplasty.  
 
Many studies have proven the advantage of utilizing TXA in anatomic and reverse TSA.  There is clear 
evidence that it is beneficial in THA and TKA and early research reveals that it will play an important role 
in decreasing bleeding after TSA. However, there have not been many studies on the benefit of TXA in 
the anticoagulated patient population. In fact, anticoagulation was previously thought to be a 
contraindication to TXA use because the TXA might increase the clotting risk that the anticoagulation is 
meant to prevent. Recent data, however, confirmed the safety of administereing TXA to anticoagulated 
patients following hip and knee arthroplasty(Fillingham/Ramkumar et al.).  Currently, there is no data on 
whether TXA will reduce blood loss in anticolagulated patients undergoing primary anatomic and reverse 
TSA.  We propose this randomized control study comparing intravenous versus control (i.e., no TXA) in 
hopes to define the benefit of TXA in this specific subset of TSA patients. 
 
The only FDA approved usage for TXA is for heavy menstrual bleeding and short term prevention in 
patients with hemophilia. TXA has been widely used off label to reduce blood loss in a variety of surgical 
cases. In othropedics, TXA is commonly used in major spine surgery and total joint arthroplasty 
procedures. The benefit of TXA in reducing total blood loss and post operative transfusion in this 
population has been well supportd in the literature (Budge, Kuo, Fillingham, Cvetanovich).   
 
TXA is lawfully marketed and this investigation is not intended to be reported to FDA as a well-
controlled study in support of a new indication for use nor intended to be used to support any 
other significant change in the labeling for the drug. This investigation does not involve a route 
of administration or dosage level or use in a patient population or other factor that significantly 
increases the risks (or decreases the acceptability of the risks) associated with the use of the drug 
product. This investigation is conducted in compliance with the requirements for institutional 
review set forth in part 56 and with the requirements for informed consent set forth in part 50. 
This investigation is conducted in compliance with the requirements of 312.7 (re: promotion of 
investigational drugs 
 
2.1 
Specific Aims 
 
AIM:  To determine if the use of IV TXA results in a quantifiable decrease in perioperative calculated 
total blood loss and transfusion requirements in anticoagulated patients undergoing TSA. 
 
2.2 
Statistical Hypotheses     
            We hypothesize that patients who receive 2 doses of intravenous TXA will have a greater reduction 
in calculated total blood loss compared with patients who receive no TXA. Furthermore, intravenous TXA 
will be more effective in decreasing post op hematoma formation in comparison to the control group. 
  
 Objectives and Purpose 
The goal of this study is to compare the effectiveness of  IV TXA vs control at reducing post-operative 
blood loss.   
 


Study number: S20-00803 
 
Page 9 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Primary outcomes measures will be calculated total blood loss and post op drain output, where the surgical 
drain output will be recorded by floor nurse every 8 hours in EPIC. 
 
Secondary outcomes include formation of hematoma, need for blood transfusions and any other adverse 
events such development of DVT, PE, MI etc, that may occur. 
3 
Study Design and Endpoints 
 
Arm #1: IV TXA 
 (2 DOSES)  
Arm #2: CONTROL 
GROUP 
 
Sample Size:  41 Subjects  
 
 
Sample Size: 41 subjects 
Medication: IV Tranxemic Acid 
None (No TXA)  
 
Total Dosage: 2 grams  
 
1 gram before surgical incision  
+ 
1 gram, 3 hours after first dose  
 
 
 
N/A  
 
3.1 
Description of Study Design 
 
PRE-SCREENING PHASE/CONSENTING PHASE: 
 
Surgeons will inform eligible patients of the study during their pre-surgical visit in their office. Potential 
participants will be able to take the informed consent home to read through and take sufficient time to ask 
questions and/or discuss with family or research team prior to making an informed decision to participate. 
If the patient is agreeable, a member of the research team will provide further details and ask the patient 
to participate on day of surgery.  An authorized research member will obtain informed consent prior to 
surgery.  
 
RANDOMIZATION PHASE:  
 
Subjects scheduled to undergo  TSA (anatomic and reverse) will be randomized to receive one of two 
treatment options. This study will utilize a simple randomization approach to generate two-equal groups. 
All subjects have an equal chance (1:2) of getting randomized into one of the twp treatments groups: (1) 
Two doses of IV TXA, one before incision and the second 3 hours later. (2) control group – no TXA given. 
Randomization of each subject will be done on day of surgery. The randomization schedule will be 
generated using a computer software program such as randomization.com 
 
TREATMENT PHASE:  
 
Subjects randomized to group 1 will receive an injection of 1 gram of  IV TXA before surgical incision 
plus 1 gram of TXA IV 3 hours later. Subjects randmomized to group 2 will receive no TXA. Neither the 
anesthesiologist or surgeon will be blinded to the patient’s group assignment, as they will be the one 


Study number: S20-00803 
 
Page 10 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
performing the treatment.  All other stakeholders (patient, other caregivers, and research staff collecting 
the data) will be blinded to the patient’s group assignment. 
 
INTRA-OPERATIVE PHASE:  
 
All patients will receive an interscalene nerve block plus or minus general anesthesia. For the procedure, 
the surgeon will utilize a deltopectoral approach and use electrocautery for hemostasis throughout the 
procedure. A subscapularis tenotomy will be performed for intraarticular access and repaired at the 
conclusion of the case for all TSA and some reverse TSA cases.  
 
Hemovac Drain:  
Lastly, a single Hemovac drain will be placed at the end of the procedure, deep to the deltopectoral interval 
and will be removed prior to discharge on POD 1. 
 
POST-OPERATIVE PHASE:  
 
The PACU nurse will administer the second dose of TXA for the patients who are in the second arm of 
TXA study, 3 hours after the first dose was administered.  
 
Hemoglobin Levels  
 
On POD 1,  the floor nurse will draw and send a post op hemoglobin/hematocrit panel for all study 
patients prior to discharge.   
 
Hemovac Surgical Output:  
 
The floor nurse will also document the amount of blood in the indwelling hemovac surgical drain placed 
in the operative shoulder joint. The drain output will be documented every 8 hours in EPIC.  Since many 
patients are discharged home on POD 1, we will record the drain output for the first 16 hours after surgery 
– essentially 2 output shifts.  If patients are in the hospital longer, we will record the third 24 hour drain 
output. 
 
Hematoma:  
 
The Orthopedic resident or fellow will assess for the presence of  hematoma on POD 1, prior to patient 
discharge.  The surgeon will assess for presence of hematoma at the 2-week follow up visit. 
 
Total calculated blood loss:  
 
The volume of perioperative blood loss will be determined on the basis of the blood volume and change 
in hemoglobin from preoperatively to 1 day postoperatively.  
 
Blood Volume:  
 
Blood volume will be calculated using Nadler’s formula.  (Cventovich, Fillingham, Abildgard, 
Tsukada, Nadler) We will calculate the predicted blood volume of each patient according to the 
formula: 
 
 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 (𝐿𝐿) =  (𝑘𝑘1 𝑥𝑥 ℎ𝑒𝑒𝑒𝑒𝑒𝑒ℎ𝑡𝑡 [𝑚𝑚]3 ) +  (𝑘𝑘2 𝑥𝑥 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑤𝑤𝑤𝑤𝑤𝑤𝑤𝑤ℎ𝑡𝑡 [𝑘𝑘𝑘𝑘]) +  𝑘𝑘3  
 


Study number: S20-00803 
 
Page 11 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
In this formula, k1 =  0.3669 for men and 0.3561 for women, k2 =  0.03219 for men and 
0.03308 for women, and k3 =  0.6041 for men and 0.1833 for women 
 
 
Change in hemoglobin: 
 
We will estimate the loss of hemoglobin (Hb) according to the formula:  
 
𝐻𝐻𝐻𝐻 𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙=   𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑚𝑚𝑒𝑒 𝑥𝑥 (𝐻𝐻𝐻𝐻𝑖𝑖 – 𝐻𝐻𝐻𝐻 𝑒𝑒) 𝑥𝑥  0.001 + 𝐻𝐻𝐻𝐻 𝑡𝑡. 
 
In this formula, Hbloss (g) =  the amount of hemoglobin lost through postoperative day 1, Hbi  
(g/L) =  the hemoglobin concentration preop, Hbe (g/L) =  the hemoglobin concentration on 
postoperative day 1, and Hbt  (g/L) =  the amount of hemoglobin transfused. 
 
 
The volume of total perioperative blood loss will be determined according to the following formula:   
 
𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙 (𝑚𝑚𝑚𝑚) =  1000 𝑥𝑥 𝐻𝐻𝐻𝐻𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙
𝐻𝐻𝐻𝐻𝑖𝑖
 
 
Transfusion Criteria 
 
All post op transfusions will be based on the recommendations from the American Association of Blood 
Banks to help reduce investigator bias secondary to unblinded staff. (Fillingham, Carson)  
Patients will only receive a blood transfusion under the following circumstances 
1. Patient Hgb is less than 7g/dl or symptomatic and not responsive to IV fluid hydration 
2. Patient has a history of cardiac disease and Hgb is less than 8g/dl or symptomatic and not 
responsive to IV fluid hydration 
Patient has an active arterial thromboemebolic event or sepsis and Hgb is less than 10g/dl or symptomatic 
and not responsive to IV fluid hydration.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study number: S20-00803 
 
Page 12 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
 
 
 
 
 
3.2 
Schematic of Study Design 
 
 
82 subjects: Obtain informed consent. Screen potential subjects by inclusion and 
exclusion criteria; obtain history, PreOP Hgb, administer medical health history form  
Randomize 
Surgical drain output, calculated total blood loss 
Hematoma formation, Need for transfusion 
Post- OP 
Enrollment 
GROUP 1 
 
IV TXA (2 doses) 
2 grams of TXA        
41 Subjects 
GROUP 2 
 
Control Group  
No TXA  
41 Subjects 


Study number: S20-00803 
 
Page 13 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
4 
Study Enrollment and Withdrawal 
The researchers will approach patients scheduled for primary total shoulder arthroplasty (anatomic and 
reverse) who are eligible for participation in the study. Anesthesiology attendings, fellows, residents and 
authorized researchers will consent and enroll patients pre-operatively. 
4.1 
Inclusion Criteria 
1. 
Patients older than 18 years old  
2. 
Patients undergoing scheduled primary anatomic total shoulder arthroplasty 
3. 
Patients undergoing scheduled primary reverse total shoulder arthroplasty 
4. 
Patients who consent to be randomized 
5. 
Preoperative use of anticoagulant or antiplatelet therapy within 10 days prior to surgery 
o Coumadin (Warfarin)  
o Heparin 
o Low molecular weight heparin 
o Factor Xa inhibitors  
 
Apixaban (Eliquis)  
 
Rivarixaban (Xatelto)  
 
Edoxaban (Savaysa)  
 
Dabigatran (Pradaxa)  
o Clopidogrel (Plavix)  
o Prasugrel (Effient) 
o Ticagrelor (Brilinta) 
 
4.2 
Exclusion Criteria 
1. Patients younger than 18  
2. Patients who are pregnant* or breast-feeding women 
3. Patients who are allergic to tranexamic acid 
4. Patients scheduled for revision total shoulder arthroplasty 
5. Patients with proximal humerus fracture or fracture sequelae 
6. Patients who use estrogen containing medications (i.e. oral contraceptive pills) 
7. Patients who have acquired disturbances of color vision  
8. Patients with a history of any of the following diagnosis: `  
o Subarachnoid hemorrhage 
o Active intravascular clotting 
o Severe pulmonary disease (FEV <50% normal) 
o Plasma creatinine > 115 μmol/L in males, > 100 μmol/L in females, or hepatic failure)  
o (Renal impairment serum creatinine > 1.5 times the upper limit of normal NYU) 
o Preoperative anemia [Hemoglobin (Hb) < 11g/dL in females, Hb < 12 g/dL in males] 
9. Patients who refuse blood products 
10. 
Patients undergoing hormone replacement therapy 
11. 
Patients with diagnosed or self-reported cognitive dysfunction; 
12. 
Patients who are unable to understand or follow instructions; 
13. 
Patients with severe liver disease, renal insufficiency, congestive heart failure, and/or significant 
heart disease; 
14. 
Patients with BMI over 50  
15. 
Any patient that the investigators feel cannot comply with all study related procedures. 


Study number: S20-00803 
 
Page 14 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
4.3 
Vulnerable Subjects 
No vulnerable populations will be intentionally solicited.  
4.4 
Recruitment and Consent 
 
This study will utilize EPIC to identify subjects and use the MCIT-managed HIPAA-compliant and 
encrypted version of Redcap in addition to the MCIT governed, firewall protected shared drive located on 
the NYU MCIT network, to manage and store relevant data.   
 
Process of Consent 
 
During the subject’s pre-surgical office visit, the surgeon will inform eligible patients about the study. 
Participants will be able to take a copy of the informed consent home to read through and take sufficient 
time to ask questions,  discuss with family and/or research team prior to making an informed decision to 
participate on day of surgery.On day of surgery, informed consent will be obtained by a member of the 
research team after extensive discussion of risks and possible benefits of participation with the participants 
and their families. Consent forms will be IRB-approved and the participant will be asked to read and 
review the document. The presenter will explain the research study to the participant and answer any 
questions that may arise. All participants will receive a verbal explanation suited to their comprehension 
of the purposes, procedures, potential risks and their rights as research participants. Participants will have 
the opportunity to carefully review the written consent form and ask questions prior to signing. The 
participants will have the opportunity to discuss the study with their family or think about it prior to 
agreeing to participate. The participant will sign the informed consent document prior to any procedures 
being done specifically for the study. The participants may withdraw consent at any time throughout the 
course of the trial. A copy of the signed informed consent document will be offered to the participants for 
their records, a copy will be scanned into the subject’s EMR, and the research staff will maintain a copy. 
The rights and welfare of the participants will be protected by emphasizing that the quality of their medical 
care will not be adversely affected if they decline to participate in this study. 
 
A copy of the signed informed consent document will be offered to the patient, placed in the patient’s 
electronic medical record and the original copy will be stored in the research regulatory binder.  Any 
alteration to the standard consent process (e.g. use of an interpreter, consent document presented orally, 
etc.) and the justification for such alteration will likewise be documented.  
 
Subject Capacity 
All subjects will be assessed for capacity to give informed consent by the anesthesiologist and the surgeon 
on the  day of surgery. Capacity will be assessed through the subjects’ ability to express understanding of 
the information presented to them, their ability to express a choice, their appreciation of how the study is 
relevant to them, and reasoning about how the study might impact them and others.  
 
If a subject requests information regarding opting out of further recruitment for all research, subjects will 
be directed to contact the PI, Dr. Arthur Hertling at 212-598-6085.  
4.5 
Duration of Study Participation 
While the study will be open for 3 years after beginning enrollment, the actual length of a study subject’s 
participation is up to two weeks, as this corresponds with the surgical follow up visit, where the surgeon 
determines if the patient developed a post op hematoma.  


Study number: S20-00803 
 
Page 15 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
4.6 
Total Number of Participants and Sites  
In order to assess the superiority of the group receiving 2 g of TXA compared to control, we consulted the 
literature. In Vara (2017), in 102 patients, we determined that the mean calculated total blood loss was 
1122.4 mL with a standard deviation of 411.6 in the TXA group vs. 1472.6 +/- 475.4 in the control group. 
Using the power equation with a SD of 444.6, an alpha of 0.05 and a power of 0.9, we estimate that 34 
patients will be needed per group. Accounting for a possible attrition of up to 20%, we will aim to recruit 
41 patients per group, or a total of 82 patients. 
 
There is a single location for enrollment, NYU Langone Orthopedic Hospital. 
 
4.7 
Participant Withdrawal or Termination 
 
Participants are free to withdraw from participation in the study at any time upon request. An investigator 
may terminate participation in the study if: 
 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation 
4.8 
Premature Termination or Suspension of Study 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. If the study is prematurely terminated or suspended, the PI will promptly inform the IRB and will 
provide the reason(s) for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
1. 
Determination of unexpected, significant, or unacceptable risk to participants; 
2. 
Insufficient compliance to protocol requirements; 
3. 
Data that are not sufficiently complete and/or evaluable; or 
5 
Risks and Benefits  
5.1 
Potential Risks  
 
Medication:  
 
 Risks of Intravenous TXA .  
 
TXA works by preventing the breakdown of fibrin so there is a theoretical risk of thromboembolic events 
such as VTE, PE, MI with vascular stents, cerebral vascular occluisve  disease. In patients using hormonal 
contraception, there is an increased risk of developing thromboembolic adverse reactions.  TXA can cause 
visual disturbances. There is also a risk of seizures after TXA administration. Lastly, TXA can cause 
hypersentivity reactions. 
Potential Benefits 
 
It is possible that study subjects who receive IV TXA may experience reduced incidence of hematoma, 
blood loss and blood transfusion during the study. It is also possible that subjects may not get any benefit 


Study number: S20-00803 
 
Page 16 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
from being in this research study. The study will help us optimize the TXA treatment protocol for future 
patients. The knowledge gained from doing this study may benefit other patients in the future.  
6 
Statistical Analysis 
6.1 
General Approach 
Intention-to-treat. The primary analysis will follow the intention-to-treat (ITT) principle in order to 
evaluate the true outcome of the intervention as experienced by the patient who is blinded to the 
intervention. 
 
Missing Data. It is anticipated that the data for some subjects will be incomplete for various reasons: 
incorrect or missing data collection from OR nurse or floor nurses. All occurrences of incomplete data 
will be investigated to carefully document the reasons for the missing data. If the primary outcome, post 
op hemoglobin, surgical drain output cannot be ascertained with a reasonable degree of certainty, the 
patient will be excluded from the study. 
6.2 
Analysis of Endpoints 
 
Primary Endpoints: 
• 
Calculated total blood loss (based on the change in pre-operative to POD 1 hemoglobin levels) 
• 
Surgical drain output  (0-24 hours post op )  
 
Secondary Endpoints: 
• 
Formation of Hematoma  (At 2 week follow up visit. YES or NO) 
• 
Need for Post op blood transfusion  
• 
Operative time 
• 
Development of adverse events , MI, PE, DVT 
 
All endpoints will be evaluated as fits the data set with graphical figures such as scatter plots, box-and-
whisker plots, and frequency histograms to visualize the distribution of these outcomes and their 
relationships to covariates and treatment assignment. When appropriate descriptive graphical and tabular 
methods will also be estimated and presented in a graphical figure. 
6.2.1 
Baseline Descriptive Statistics 
The following patient data will be recorded: age, gender, height, weight, date of admission, date of 
discharge, laterality, surgical approach, implants used, duration of surgery, contamination, ASA, 
comorbidities (smoking, cardiac history, diabetes etc.), CBC (WBC, PCV, HGB, RBC, indices, platelet 
count, differential), and medications. All of this information will be accessible in the patient’s medical 
record. Descriptive statistics will be used to summarize variables with mean and standard deviation for 
continuous variables, or percentages for categorical variables.  
 
Sample Size:  
 
Power analysis was performed for the primary outcome of total blood loss (See 4.6). 
 
The primary outcome of total blood loss will be tested using two one sided t-tests (TOST) for equivalence 
testing between intervention groups whereby a p-value of <0.05 represents statistical equivalence.  
Addiitonally, demographical and baseline comparisons between intervention groups will be made usisng 


Study number: S20-00803 
 
Page 17 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
an analysis os variance (ANOVA) for continuous measurements or a chi-squared or Fischer’s exact test 
for categorical variables.  Significance will be set at a p-value of <0.05 
6.3 
Enrollment/Randomization/Masking Procedures 
We will utilize a simple-randomization method to create two equal groups of subjects as mentioned in the 
schematic study design (3.2). Additionally, we will use a computer software, randomization.com,  to 
generate the randomization assignment for all participants.  Someone that is not a stakeholder in the study 
will make randomization opaque envelopes, which includes the study ID number, the treatment 
assignment, and dosage specifics. These randomization envelopes will then be distributed to the 
anesthesiologist pre-operatively by the authorized researcher after informed consent is obtained.  
6.4 
Breaking the Study Blind/Participant Code 
If there is any adverse event related to the drug, we will break the blind for the subject and randomization 
will be disclosed to the patient. 
7 
Assessment of Safety 
 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• 
results in study withdrawal 
• 
is associated with a serious adverse event 
• 
is associated with clinical signs or symptoms 
• 
leads to additional treatment or to further diagnostic tests 
• 
is considered by the investigator to be of clinical significance 
 
7.1 
Definition of Serious Adverse Events (SAE) 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• 
fatal 
• 
life-threatening 
• 
requires or prolongs hospital stay 
• 
results in persistent or significant disability or incapacity 
• 
a congenital anomaly or birth defect 
• 
an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance. They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above. For example, drug overdose or abuse, a seizure that did not result in 
in-patient hospitalization or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious will be regarded as non-serious adverse 
events.  


Study number: S20-00803 
 
Page 18 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
7.2 
Classification of an Adverse Event 
7.2.1 
Severity of Event 
 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity. 
 
1. Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
2. Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
3. Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy 
or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
7.2.2 
Relationship to Study Agent 
 
The clinician’s assessment of an AE's relationship to study agent (drug, biologic, device) is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the study. If there 
is any doubt as to whether a clinical observation is an AE, the event will be reported. All AEs must have 
their relationship to study agent assessed.. For all collected AEs, the clinician who examines and evaluates 
the participant will determine the AE’s causality based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below. 
1. Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, 
occurs in a plausible time relationship to drug administration and cannot be explained by concurrent 
disease or other drugs or chemicals.  
2. Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the drug, is unlikely to be attributed to concurrent disease or 
other drugs or chemicals, and follows a clinically reasonable response on withdrawal).  
3. Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication). However, other factors may have 
contributed to the event (e.g., the participant’s clinical condition, other concomitant events). Although 
an AE may rate only as “possibly related” soon after discovery, it can be flagged as requiring more 
information and later be upgraded to “probably related” or “definitely related,” as appropriate. 
4. Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to drug administration makes a causal relationship improbable (e.g., the event did not 
occur within a reasonable time after administration of the trial medication) and in which other drugs 
or chemicals or underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments). 
5. Not Related – The AE is completely independent of study drug administration, and/or evidence exists 
that the event is definitely related to another etiology. There must be an alternative, definitive etiology 
documented by the clinician. 
 
Dr. Arthur Hertling will be responsible for determining whether an AE is expected or unexpected. An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not consistent with the 
risk information previously described for the study agent. 


Study number: S20-00803 
 
Page 19 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
7.3 
Time Period and Frequency for Event Assessment and Follow-Up 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the appropriate 
RF. Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 
during the study, it will be recorded as an AE. UPs will be recorded in the data collection system 
throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of onset 
and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At 
each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. Events 
will be followed for outcome information until resolution or stabilization. As per NYU IRB policy, we 
will abide by the time frame for reporting AE/SAE’s. The time frame for reporting SAE and UP to the 
DSMB is by telephone within 24 hours of awareness of the event. The time frame for reporting SAE and 
UP to the IRB is to submit reports promptly but no later than 5 working days from the time the investigator 
becomes aware of the event.  
 
All unresolved adverse events will be followed by the investigator until the events are resolved, the subject 
is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the investigator 
will instruct each subject to report any subsequent event(s) that the subject, or the subject’s personal 
physician, believes might reasonably be related to participation in this study.  The investigator will notify 
the medical center IRB  of any death or adverse event occurring at any time after a subject has discontinued 
or terminated study participation that may reasonably be related to this study.  The medical center IRB 
will also be notified if the investigator should become aware of the development of cancer or of a 
congenital anomaly in a subsequently conceived offspring of a subject that has participated in this study. 
These events are highly unlikely given that local anesthestics are relatively safe drugs and are not known 
to be carcinogenic or teratogenic. 
 
7.4 
Safety Oversight  
 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her site.  This 
safety monitoring will include careful assessment and appropriate reporting of adverse events as noted 
above, as well as the construction and implementation of a site data and safety-monitoring plan. Medical 
monitoring will include a regular assessment of the number and type of serious adverse events. 
Additionally, the study will have a DSMB. 
 


Study number: S20-00803 
 
Page 20 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
The DSMB will be made up of the Principal Investigator, Arthur C. Hertling M.D. and Co-investigator, 
Young Kwon M.D. All members of the DSMB are board certified physicians in their respective specialties 
– Anesthesiology and Orthopedic Surgery.  
 
The DSMB will review safety data after the first five enrolled subjects and every three months thereafter. 
All unanticipated problems that increase risk to the subjects will be reported to the IRB per NYUSOM 
IRB policy.  
 
During these meetings, the DSMB will review and analyze any unanticipated problems or adverse events 
involving risk to the patient including thromboembolic events such as VTE, PE, MI with vascular stents, 
cerebral vascular occluisve disease. 
 
Specific study stopping points is the occurrence of a serious adverse event such as a severe allergic reaction 
to TXA. Additionally, after 5 patients in each group have completed all study related procedures, a brief 
safety analysis will be done by the Principal Investigator, Arthur C. Hertling M.D.  Events will be reported 
to the anesthesia department QA.  
Additionally, the DSMB will perform an interim safety and data analysis after 40 patients have completed 
all study related visits.  Outcomes of these reviews will be submitted to the IRB in an annual progress 
report at the time of Continuing Review. 
 
8 
Source Documents and Access to Source Data/Documents  
 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in 
source documents.  Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified 
after verification as being accurate and complete, microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-
technical departments involved in the clinical trial.  
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
requested on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is left 
blank because the procedure was not done or the question was not asked, write “N/D”.  If the item is not 
applicable to the individual case, write “N/A”.  All entries will be printed legibly in black ink.  
 
Access to study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government 
regulatory bodies, and University compliance and quality assurance groups of all study related documents 
(e.g. source documents, regulatory documents, data collection instruments, study data etc.).  The 
investigator will ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.). 
 


Study number: S20-00803 
 
Page 21 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
9 
Ethics/Protection of Human Subjects 
9.1 
Ethical Standard 
 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
and/or the ICH E6. 
9.2 
Institutional Review Board 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented participants 
need to be re-consented. 
9.3 
Participant and Data Confidentiality 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval of the sponsor. 
 
The study monitor, representatives of the IRB may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) 
and pharmacy records for the participants in this study. The clinical study site will permit access to such 
records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems used by 
clinical sites and by NYU Langone Medical Center research staff will be secured and password protected. 
At the end of the study, all study databases will be de-identified and archived at the NYU Langone Medical 
Center. 
 
10 Data Handling and Record Keeping 
10.1 
Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported. 


Study number: S20-00803 
 
Page 22 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 
documents should be consistent with the source documents or the discrepancies should be explained and 
captured in a progress note and maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into Redcap. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
 
 
 
 
 
10.2 
Study Records Retention 
 
Study documents will be retained for the longer of 3 years after close-out, 5 years after final 
reporting/publication, or 2 years after the last approval of a marketing application is approved for the drug 
for the indication for which it is being investigated or 2 years after the investigation is discontinued and 
FDA is notified if no application is to be filed or if the application has not been approved for such 
indication. No records will be destroyed without the written consent of the sponsor, if applicable. It is the 
responsibility of the sponsor to inform the investigator when these documents no longer need to be 
retained. 
10.3 
Protocol Deviations 
 
It is the responsibility of the site PI/study staff to use continuous vigilance to identify and report deviations 
within 7 working days of identification of the protocol deviation, or within 7 working days of the scheduled 
protocol-required activity. 
 
Protocol deviations will be reported to the local IRB per their guidelines. The site PI/study staff is 
responsible for knowing and adhering to their IRB requirements.  
10.4 
Publication and Data Sharing Policy 
 
This trial will be registered with the clinicaltrials.gov as per the ICMJE policy, and the Section 801 of the 
Food and Drug Administration Amendments Act of 2007.  


Study number: S20-00803 
 
Page 23 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
11 Study Finances 
11.1 
Funding Source 
No funding source present. 
11.2 
Costs to the Participant 
There are no expected costs to the subjects. 
11.3 
Participant Reimbursements or Payments 
Participants will not receive any financial compensation for participation in this study. 
12 Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the trial. The study leadership has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a mechanism 
for the management of all reported dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial 
gain greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the 
NYU Langone Conflict of Interest Management Unit (CIMU) with a Committee-sanctioned conflict 
management plan that has been reviewed and approved by the study sponsor prior to participation in this 
study. All NYULMC investigators will follow the applicable conflict of interest policies. 
 
 
 


Study number: S20-00803 
 
Page 24 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
13 References 
1. McCormack PL. Tranexamic acid. A Review of its use in the treatment of hyperfibrinolysis.  
Drug. 2012 Mar 26; 72 (5): 585-617 
 
2. Budge M. Topical and intravenous tranexamic acid are equivalent in decreasing blood loss in 
total shoulder arthroplasty. Journal of Shoulder and Elbow Athroplasty. 2019. 3:1-5 
 
3. Kuo LT, Hsu WH, Chi CC, Yoo JC: Tranexamic acid in total shoulder arthroplasty and reverse 
shoulder arthroplasty: A systematic review and meta-analysis. BMC Musculoskeletal 
Disorders 2018;19:60.  
 
4. Schulman S. Care of pateints receiving long term anticioagulant therapy. N Engl J Med. 2003; 
349: 675-683 
 
5. Kirsch JM, Bedi A, Horner N, Wiater JM, Pauzenberger L, Koueiter DM, et al. Tranexamic acid 
in shoulder arthroplasty: a systematic review and meta-analysis. JBJS Rev. 2017;5(9):e3. doi: 
10.2106/JBJS.RVW.17.00021 
 
6. Box, HN, Tisano, BS, Khazzam, M. Tranexamic acid administration for anatomic and reverse 
total shoulder arthroplasty: a systematic review and meta-analysis. JSES Open Access 2018; 
2: 28–33. 
 
7. Yang L, Du S, Sun Y. Is combined topical and intravenous tranexamic acid superior to single 
use of tranexamic acid in total joint arthroplasty?: A meta-analysis from randomized controlled 
trials. Medicine (Baltimore) 2017;96:e7609. 
 
8. G.L. Cvetanovich, Y.A. Fillingham, M. O'Brien, B. Forsythe, B.J. Cole, N.N. Verma, et al.  
Tranexamic acid reduces blood loss after primary shoulder arthroplasty: a double-blind, placebo-
controlled, prospective, randomized controlled trial. JSES Open Access, 2 (2018), pp. 23-27 
 
9. Fillingham YA, Darrith B, Calkins TE, Abdel MP, Malkani AL, Schwarzkopf R, Padgett DE et 
al. 2019 Mark Coventry Award: A randomized clinical trial of tranexamic acid in revision total 
knee arthroplasty. Does the dosing regimen matter?  The Bone and Joint Journal. 2019:101  
 
10. Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Bini SA, Clarke HD, Schemitsch E, 
Johnson RL, Memtsoudis SG, Sayeed SA, Sah AP, Della Valle CJ. Tranexamic Acid Use in 
Total Joint Arthroplasty: The Clinical Practice Guidelines Endorsed by the American 
Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain 
Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society. J 
Arthroplasty. 2018 Oct;33(10):3065-3069.. 
 
11. Abildgaard JT, McLemore R, Hattrup SJ. Tranexamic Acid decreases blood loss in total 
shoulder arthroplasty and reverse total shoulder arthroplasty. JSES. 2016; 25: 1643-1648 
 
12. Gillespie R, Shishani Y, Joseph S et al. Neer Award 2015: A randomized prospective evaluation 
on the effectiveness of tranexamic acid in reducing blood loss after total shoulder arthroplasty. 
JSES. 2015; 24:1679-1684 
 


Study number: S20-00803 
 
Page 25 
Version: 2.0 dated 04.21.2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
13. Vara AD, Koueiter DM, Pinkas DE et al. Intravenous TXA reduces total blood loss in reverse 
total shoulder arthroplasty: a propspective double blind randomized trial. JSES. 2017; 26:1383-
1389 
 
14. Freidman RJ, Gordon E, Butler B et al. Tranexamic acid decreases blood loss after total shoulder 
arthroplasty. JSES. 2016; 25: 614-618 
 
15. Tsukada S,  Kurosaka K, Nishino M et al. Intraoperative Inatravenous and intra-articular plus 
postoperative intravenous tranexamic acid in total knee arthroplasty. JBJS. 2020; 102: 687-92 
 
16. Carson JL, Grossman BJ, Kleinman S, et al. Red blood cell transfusion: a clinical practice 
guideline from the AABB* Ann Intern Med 2012;157:49-58 
 
17. Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery. 
1962 Feb;51(2):224-32.