Tranexamic Acid in Reverse Total Shoulder Arthroplasty

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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02043132

Acronym

TXA

Enrollment

116

Registered

2014-01-23

Start date

2013-09-30

Completion date

2016-02-29

Last updated

2017-06-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Blood Loss, Surgical, Complications; Arthroplasty, Intraoperative Complications, Shoulder Joint Disease

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

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.

Interventions

DRUGTranexamic 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.

DRUGPlacebo

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Total Blood Loss	Preoperative through Postoperative Days 1 and 2	Total Blood Loss as calculated according to method as described by Good et al. Total Blood Loss (mL) = 1000 X Hb(loss)/Hb(initial)
Total Hemoglobin Loss	Preoperative through Postoperative Days 1 and 2	Total hemoglobin loss estimated using the formula for total blood volume described by Nadler et al Hb(loss) = blood volume (L) x \[Hb(initial)(g/L) - Hb(final)(g/L)\] + Hb(transfused)
Total Drain Output	0-48 hours postoperatively	Total Drain Output as measured postoperatively 0-48 hours

Secondary

Measure	Time frame	Description
Number of Participants Experiencing Hematoma as a Surgical Site Complication	up to 6-weeks post-operatively	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
Number of Participants Experiencing Pulmonary Embolism	up to 6-weeks post-operatively	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
Number of Participants Experiencing Infection as a Surgical Site Complication	up to 6-weeks post-operatively	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
Number of Participants Experiencing Myocardial Infarction	up to 6-weeks post-operatively	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
Number of Participants Experiencing Deep Vein Thrombosis	up to 6-weeks post-operatively	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

Countries

United States

Participant flow

Pre-assignment details

116 participants were consented; 2 were lost to follow-up and 12 were screen failures. These 14 participants were excluded from the overall data analysis, therefore 102 completed participants were analyzed.

Participants by arm

Arm	Count
Tranexamic Acid Infusion Tranexamic acid on study subjects. They will be randomized to receive an infusion of the standard dose of Tranexamic acid (10mg/kg) One dose will be given by the bedside nurse within 60 minutes prior to surgery and a second dose will be given at wound closure. Infusion will be given along with standard preoperative and operative infusion; no additional infusion will be necessary. 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.	53
Normal Saline Infusion of placebo on study subjects. They will be randomized to receive an infusion of placebo (an equivalent volume of normal saline). One dose will be given by the bedside nurse within 60 minutes prior to surgery and a second dose will be given at wound closure. Infusion will be given along with standard preoperative and operative infusion; no additional infusion will be necessary. 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.	49
Total	102

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	1
Overall Study	screen failures	4	8

Baseline characteristics

Characteristic	Tranexamic Acid	Normal Saline	Total
Age, Continuous	67 years STANDARD_DEVIATION 9	66 years STANDARD_DEVIATION 9	67 years STANDARD_DEVIATION 9
Region of Enrollment United States	53 participants	49 participants	102 participants
Sex: Female, Male Female	33 Participants	27 Participants	60 Participants
Sex: Female, Male Male	20 Participants	22 Participants	42 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 53	0 / 49
other Total, other adverse events	1 / 53	1 / 49
serious Total, serious adverse events	0 / 53	1 / 49

Outcome results

Primary

Total Blood Loss

Total Blood Loss as calculated according to method as described by Good et al. Total Blood Loss (mL) = 1000 X Hb(loss)/Hb(initial)

Time frame: Preoperative through Postoperative Days 1 and 2

Arm	Measure	Value (MEAN)	Dispersion
Tranexamic Acid	Total Blood Loss	1122.4 Total Blood Loss (mL)	Standard Deviation 411.6
Normal Saline	Total Blood Loss	1472 Total Blood Loss (mL)	Standard Deviation 475.4

Primary

Total Drain Output

Total Drain Output as measured postoperatively 0-48 hours

Time frame: 0-48 hours postoperatively

Arm	Measure	Value (MEAN)
Tranexamic Acid	Total Drain Output	221 mL
Normal Saline	Total Drain Output	372 mL

Primary

Total Hemoglobin Loss

Total hemoglobin loss estimated using the formula for total blood volume described by Nadler et al Hb(loss) = blood volume (L) x \[Hb(initial)(g/L) - Hb(final)(g/L)\] + Hb(transfused)

Time frame: Preoperative through Postoperative Days 1 and 2

Arm	Measure	Value (MEAN)
Tranexamic Acid	Total Hemoglobin Loss	154.6 g
Normal Saline	Total Hemoglobin Loss	200.1 g

Secondary

Number of Participants Experiencing Deep Vein Thrombosis

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