Tranexamic Acid in Reverse Total Shoulder Arthroplasty

Blood Loss, Surgical Clinical Trial

— TXA  

Official title:

Intravenous Tranexamic Acid to Reduce Blood Loss in Reverse Total Shoulder Arthroplasty

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02043132
• Other study ID #: 2013-060
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 15, 2014
• Last updated: June 14, 2016
• Start date: September 2013
• Est. completion date: February 2016

Study information

• Verified date: June 2016
• Source: William Beaumont Hospitals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Loss, Surgical
• Complications; Arthroplasty
• Hemorrhage
• Intraoperative Complications
• Joint Diseases
• Shoulder Joint Disease

Intervention

Drug:
• Tranexamic Acid
Patients randomized to TXA receive an infusion of the standard dose of Tranexamic acid (10 mg/kg) within 60 minutes prior to surgery and at wound closure. The pharmacy uses the randomization list in sequential order to determine whether that patient will receive Tranexamic acid or placebo and will provide two unlabeled IV bags (patient receives two doses) of the appropriate solution.
• Placebo
Patients randomized to placebo receive an infusion of 10 mg/kg of normal saline within 60 minutes prior to surgery and at wound closure. The pharmacy uses the randomization list in sequential order to determine whether that patient will receive Tranexamic acid or placebo and will provide two unlabeled IV bags (patient receives two doses) of the appropriate solution.

Locations

Country	Name	City	State
United States	William Beaumont Hospital	Royal Oak	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
William Beaumont Hospitals

Country where clinical trial is conducted

United States, 

References & Publications (40)

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Perioperative blood loss	The minimum hemoglobin in the postoperative period (Hbmin (g/L)) will be compared to the preoperative baseline levels. Total hemoglobin loss in grams will be estimated using the formula for total blood volume and by the method of Good et al.; Blood Volume (mL) Total blood Loss (mL) Intraoperative blood loss (total volume of cell-saver transfused) + total drain output Total number of postoperative transfusions	Surgery start time to 36 hours post start time	Yes
Secondary	systemic complication	The occurrence of the following systemic and surgical site complications within 6 weeks of surgery will be recorded. Data will be obtained from EMR and from patient at standard of care 2 week and 6 week follow-up appointment.; Pulmonary Embolism	up to 6-weeks post-operatively	Yes
Secondary	systemic complication	The occurrence of the following systemic and surgical site complications within 6 weeks of surgery will be recorded. Data will be obtained from EMR and from patient at standard of care 2 week and 6 week follow-up appointment.; Myocardial infarction	up to 6-weeks post-operatively	Yes
Secondary	Systemic complication	The occurrence of the following systemic and surgical site complications within 6 weeks of surgery will be recorded. Data will be obtained from EMR and from patient at standard of care 2 week and 6 week follow-up appointment.; Deep venous thrombosis	up to 6-weeks post-operatively	Yes
Secondary	Surgical site complication	The occurrence of the following systemic and surgical site complications within 6 weeks of surgery will be recorded. Data will be obtained from EMR and from patient at standard of care 2 week and 6 week follow-up appointment.; Hematoma	up to 6-weeks post-operatively	Yes
Secondary	Surgical site complication	The occurrence of the following systemic and surgical site complications within 6 weeks of surgery will be recorded. Data will be obtained from EMR and from patient at standard of care 2 week and 6 week follow-up appointment.; Infection	up to 6-weeks post-operatively	Yes
Secondary	Myocardial infarction indicator CK-MB	CK-MB of 100 µg/L or more	up to 6 weeks post-operatively	Yes
Secondary	myocardial infarction indicator Troponin	troponin-I of 3.0 µg/L or more	up to 6-weeks post-operatively	Yes
Secondary	Myocardial Infarction indicator EKG	Appearance of new postoperative Q waves on the EKG of more than 0.03 seconds	up to 6-weeks postoperatively	Yes
Secondary	Myocardial infarction indicator Echocardiogram	A new hypokinetic or akinetic area in the left or right ventricle by echocardiography	up to 6-weeks post-operatively	Yes