Clinical trial NCT02043132: Tranexamic Acid in Reverse Total Shoulder Arthroplasty
Official title: Intravenous Tranexamic Acid to Reduce Blood Loss in Reverse Total Shoulder Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Shoulder Joint Disease
Complications; Arthroplasty
Intraoperative Complications
Blood Loss, Surgical
Keywords: reverse shoulder arthroplasty
Rotator cuff
Orthopedic joint surgery
Total shoulder
Perioperative bleeding
Tranexamic acid
Orthopedic complications
Hemorrhage
Postoperative Hemorrhage
Pathologic Processes
Arthritis
Joint Diseases
Musculoskeletal Diseases
Postoperative Complications
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Lead sponsor: William Beaumont Hospitals
Sponsor class: OTHER
First posted: 2014-01-23
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To the Investigators' knowledge, TXA has not been studied in the setting of reverse total shoulder arthroplasty. We propose a double-blinded, randomized, controlled trial comparing perioperative administration of TXA to placebo in the setting of RTSA. The purpose of this study is to examine the efficacy of TXA in reducing overall blood loss and transfusion rates in patients undergoing reverse total shoulder arthroplasty.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total Blood Loss
timeFrame: Preoperative through Postoperative Days 1 and 2
measure: Total Hemoglobin Loss
timeFrame: Preoperative through Postoperative Days 1 and 2
measure: Total Drain Output
timeFrame: 0-48 hours postoperatively
Secondary outcomes:
measure: Number of Participants Experiencing Pulmonary Embolism
timeFrame: up to 6-weeks post-operatively
measure: Number of Participants Experiencing Myocardial Infarction
timeFrame: up to 6-weeks post-operatively
measure: Number of Participants Experiencing Deep Vein Thrombosis
timeFrame: up to 6-weeks post-operatively
measure: Number of Participants Experiencing Hematoma as a Surgical Site Complication
timeFrame: up to 6-weeks post-operatively
measure: Number of Participants Experiencing Infection as a Surgical Site Complication
timeFrame: up to 6-weeks post-operatively
Other outcomes:
Locations:
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
Study officials:
affiliation: William Beaumont Hospitals
name: Michael J Wiater, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: William Beaumont Hospitals
name: Kevin Baker, PhD
role: STUDY_DIRECTOR
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