Tranexamic Acid in Reverse Total Shoulder Arthroplasty

Shoulder arthroplasty is a procedure used to relieve pain and dysfunction associated with
arthritic destruction of the gleno-humeral joint. It has been demonstrated that in patients
with concomitant rotator cuff deficiency, reverse total shoulder arthroplasty (rTSA) is an
efficacious procedure that relieves pain as well as increases the lever-arm of the deltoid
muscle, thus improving post-operative strength and range of motion.

However, perioperative blood loss in total shoulder arthroplasty can be significant, with an
overall rate of allogeneic blood transfusion reported to be 7.4%-43% [1-5]. Patients
undergoing reverse total shoulder arthroplasty are at even further risk of requiring a
postoperative blood transfusion [2]. Blood transfusions are associated with significant
risks to patient health that range from mild to life threatening.

Tranexamic acid (TXA) is an antifibrinolytic medication (reduces the destruction of blood
clots, thus promoting the ability to stop bleeding) that is frequently used to reduce
perioperative blood loss, blood transfusions and associated costs in major cardiac,
vascular, obstetric, and orthopedic procedures. Currently, 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) [11-33].
Multiple recent meta-analyses have found that use of TXA in the setting of TKA and THA leads
to significantly less overall blood loss and lower rates of blood transfusion without
increasing rates of venous thromboembolism (VTE) or other complications [34-37]. TXA is now
on formulary at William Beaumont Hospital.

100 patients slated to undergo elective reverse total shoulder arthroplasty will be
recruited and randomized to receive either an infusion of the standard dose of TXA (10mg/kg)
or placebo (an equivalent volume of normal saline) within 60 minutes prior to surgery and at
wound closure.

Adult subjects 18 years of age or older will participate in this study after the objectives,
methods, and potential hazards of the study have been fully explained, and after they have
signed the informed consent form. The Investigator or designee is responsible for keeping a
record of all subjects who sign an informed consent form for entry into this study

DATA AND SAFETY MONITORING PLAN Beaumont Research will follow their standard operating
policy and procedure for establishing a group of designated Beaumont Hospital faculty that
will be responsible for data and safety monitoring. This group will include a clinician,
physician, scientific member and statistician. They will meet twice throughout the course of
the study. A medical monitor was not appointed since this is a single-site study; Dr. J.
Michael Wiater will personally oversee the health and well-being of all patients and submit
AE reports, and the designated group will directly review all adverse event reports.
Beaumont's Human Investigation Committee will review the data safety monitoring plan as part
of their IRB approval process.

Study data will be transcribed by study personnel from the source documents into an
electronic database maintained in Excel. The data collections forms are to be completed by
the research nurse at the time of the data collection so that they always reflect the latest
observations on the subjects participating in the study. Demographic data will be filled in
preoperatively, intraoperative blood loss will be recorded in the OR, postoperative blood
loss and transfusion will be collected retrospectively, and complications will be recorded
as they occur or at 2 and 6 week follow-up. All data entries, corrections and alterations
must be made by the investigator or other authorized study personnel. The Research Institute
will complete internal auditing at random intervals during the study for data integrity,
proper informed consent process implementation and documentation, protocol adherence, and
patient safety reporting compliance to regulatory bodies.

Descriptive statistics will be provided for all data collected. Missing data will remain
missing and will not be replaced by substitutions or interpolations. Statistical software
(SPSS, IBM, Inc) will be used for all analyses. Baseline and demographic data will be
compared between the 2 randomization arms to determine if any imbalances exist. Categorical
variables will be shown as counts and % frequencies. They will be examined using Pearson's
Chi-square where appropriate (expected frequency>5), otherwise a Fisher's Exact test will be
used. Continuous variables will be examined for normality. Normally distributed variables
will be analyzed using t-tests and non-normally distributed variables will be examined using
non-parametric Wilcoxon rank tests. All continuous variables will be shown as means+/- the
standard deviation followed by the median and (25th, 75th percentiles) where needed.

The primary outcome of intraoperative and postoperative blood loss and postoperative drop in
Hb will be examined for normality. Normally distributed variables will be analyzed using
t-tests and non-normally distributed variables will be examined using non-parametric
Wilcoxon rank tests. Total number of postoperative transfusions and total number of patients
requiring postoperative transfusions will be shown as counts and % frequencies. They will be
examined using Pearson's Chi-square where appropriate (expected frequency>5), otherwise a
Fisher's Exact test will be used.

The secondary outcomes of systemic and surgical site complications will be examined between
the two randomization arms using Pearson's Chi-square where appropriate (expected
frequency>5), otherwise a Fisher's Exact test will be used.

Inclusion Criteria:

1. Patients undergoing scheduled primary reverse total shoulder arthroplasty performed
by J. Michael Wiater, MD.

2. Patients age 18 and older

Exclusion Criteria:

1. Pregnant* or breast-feeding women

2. Allergy to tranexamic acid

3. Acquired disturbances of color vision

4. Use of estrogen containing medications (i.e. oral contraceptive pills)

5. Hormone replacement therapy

6. Preoperative anemia [Hemoglobin (Hb) < 11g/dL in females, Hb < 12 g/dL in males]

7. Refusal of blood products

8. Preoperative use of anticoagulant therapy within 5 days prior to surgery

1. Coumadin

2. Heparin

3. Low molecular weight heparin

4. Factor Xa inhibitors

9. Thrombin inhibitors

10. Coagulopathy

11. Thrombophilia

12. Antithrombin deficiency

13. Factor V Leiden

14. Antiphospholipid Syndrome

15. Protein C and S deficiency

16. History of heparin induced thrombocytopenia

17. Sickle cell anemia

18. Myeloproliferative disorders

19. Platelet < 150,00 mm3

20. International Normalized Ratio (INR) > 1.4

21. Partial Thromboplastin Time (PTT) > 1.4 times normal

22. A history of arterial or venous thromboembolism

23. Cerebral Vascular Accident

24. Deep Vein Thrombosis

25. Pulmonary Embolism

26. Subarachnoid hemorrhage

27. Active intravascular clotting

28. Major comorbidities

29. Coronary artery disease (New York Heart Association Class III or IV)

30. Previous MI

31. Severe pulmonary disease (FEV <50% normal)

32. Plasma creatinine > 115 μmol/L in males, > 100 μmol/L in females, or hepatic failure)

34. Participation in another clinical trial 35. *All women of child bearing potential must
have a negative serum or urine pregnancy test.