Tranexamic Acid to Reduce Blood Loss in Spine Trauma Surgery

Spinal Deformity Clinical Trial

Official title:

Topical Application of Tranexamic Acid to Reduce Blood Loss During Complex Combat-related Spine Trauma Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02314988
• Other study ID #: AAAQ6795
• Secondary ID: 201409111
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 15, 2020
• Est. completion date: July 2025

Study information

• Verified date: April 2024
• Source: Columbia University
• Contact: Ronald A Lehman, MD
• Phone: 2129325067
• Email: rl2781[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the efficacy of topical tranexamic acid to reduce perioperative blood loss, reduction in postoperative drain output and allogenic transfusion requirements. The proposed study will be a prospective, randomized, double-blind (subject, surgeons, investigators, research coordinators) placebo-controlled study. Patients following high energy trauma who have sustained thoracic or lumbar spine fractures, dislocations or ligamentous injury with resultant instability requiring posterior spinal fusion will be enrolled for this study. Furthermore, patients undergoing elective complex deformity surgery will also be enrolled. Both populations of patients will be randomized into two groups. Group I will receive standard of care operative fixation with topical tranexamic acid intervention (test); Group II will receive standard of care operative fixation with normal saline (placebo) intervention. This study will have a 2-year follow-up and will consist of three periods: screening/enrollment phase up to 21 days from the day of injury to the day of randomization and operative intervention, an inpatient data collection period for 4 days postoperative, and then a follow-up period for 2-years postoperative (visits occurring at 2 week, 16 week, 1 year, and 2 year) time points.

Description:

Reducing perioperative blood loss is critically important in the treatment of multiply injured combat casualties, and major blood loss during complex spine trauma surgery is a significant concern. Similar to previous studies in dental, cardiac, and total knee arthroplasty procedures, the use of topical tranexamic acid during complex combat related spine trauma surgery can be a cost-effective and simple route of administration to reduce blood loss, with no significant systemic effects. Patients would be expected to benefit immediately by decreasing blood loss and the need for blood transfusion postoperatively, thereby exposing them to less risk of transfusion reactions or disease transmission. This may also potentially decrease the rate of surgical site infection because patients have been found to have a significantly increased risk for surgical site infection after blood transfusion due to changes in the immune system, and by also decreasing the amount of blood that collects under the surgical wound, which serves as excellent medium for bacterial growth. The goal of the investigators study is to determine if the use of topical tranexamic acid (TXA) in the setting of complex spine trauma surgery reduces blood loss, and subsequently reduces the rate of allogenic blood transfusion and surgical site infection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 252
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Thoracic or lumbar spinal column injury with or without neurologic deficit requiring surgical fixation

2. Surgical fixation to be performed within 21 days of injury

3. Adult patients undergoing long segment (>5 fusion levels) posterior spinal fusions

Exclusion Criteria:

1. Age <18 or >80 years old

2. Severe soft tissue disruption around planned surgical site preventing adequate primary wound closure

3. Physiologic instability or ongoing sepsis/infection

4. Use of intravenous tranexamic acid during the pre-study period

5. Ballistic spinal column injury

6. Allergy to tranexamic acid

7. Disturbances of color vision or color blindness

8. Pre-operative hemoglobin value of <7 g/dL, or <10 g/dL if patient has comorbidities or symptoms which will require pre-operative allogeneic blood transfusion

9. Refusal to consent for blood products

10. Participation in another clinical trial

11. Moderate or severe traumatic brain injuries that do not allow participation in individual patient outcomes surveys

12. Subarachnoid hemorrhage, anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by TXA

13. Concomitant use of Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates, as the risk of thrombosis may be increased

14. Preoperative use of anticoagulant therapy (heparin, low-molecular weight heparin, warfarin) within three days before surgery, or non-steroid inflammatory medication (aspirin, ibuprofen, naprosyn) use within seven days before surgery

15. Fibrinolytic disorders requiring intraoperative antifibrinolytic treatment

16. Disseminated intravascular coagulation (DIC)

17. Coagulopathy (as identified by a preoperative platelet count of <150,000/mm3, an international normalized ratio of >1.4, or a prolonged partial thromboplastin time >1.4 times normal)

18. History of arterial or venous thromboembolic disease (such as a cerebrovascular accident, deep-vein thrombosis, or pulmonary embolus), as these patients may be at increased risk for venous or arterial thrombosis

19. Upper urinary tract or ureteral injury (ureteral obstruction due to clot formation in patients with upper urinary tract bleeding has been reported)

20. Pregnancy or breastfeeding (Category B)

21. Substantial renal dysfunction (as assessed by a serum creatinine > 1.5 or calculated creatinine clearance of < 50) or hepatic failure

22. Major co-morbidities: alcohol or drug abuse, illnesses that affect bone or calcium metabolism, connective tissue disorders, coronary artery disease, severe ischemic heart disease [New York Heart Association Class III or IV], previous myocardial infarction, severe pulmonary disease [forced expiratory volume <50% of normal], diabetes mellitus (Type I or Type II), immunosuppression, peripheral vascular disease, severe penetrating or hemorrhagic traumatic brain injury, a history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton.

23. History of seizure or convulsive disorders, or currently concomitant use of other medications that are known to reduce seizure threshold

24. History of dural tear or open subdural space

Related Conditions & MeSH terms

• Hemorrhage
• Spinal Deformity
• Spinal Injuries

Intervention

Drug:
• Tranexamic Acid
3.0 grams of tranexamic acid will be poured in the surgical field and left in contact for five minutes. Subsequently, excess study solution will be suctioned away without touching the surrounding tissue surfaces and then the would closed without irrigation or manipulation. TXA solution will be prepared using a dose of 3 grams of tranexamic acid combined with 70 mL of sterile normal saline, for a total volume of 100 mL.
• Placebo
Placebo will be poured in the surgical field and left in contact for five minutes. Subsequently, excess solution will be suctioned away without touching the surrounding tissue surfaces and then the would closed without irrigation or manipulation. The placebo solution will be 100 mL of sterile normal saline.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina
United States	Norton Leatherman Spine Center	Louisville	Kentucky
United States	NYP/The Allen Hospital - CUIMC	New York	New York
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Madigan Army Medical Center	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal drop in systemic hemoglobin concentration during the postoperative period		Patients will be followed through postoperative day 4
Secondary	Reduction in the rate of surgical site infections	Defined by decreasing the allogenic transfusion rate (an independent risk factor for surgical site infections) as well as by decreasing the formation of postoperative hematoma (a nidus for infection).	Duration of the hospital stay (an average of 2 weeks), first postoperative wound check visit
Secondary	Number of complications	Defined as thromboembolic event, including deep vein thrombosis (DVT) or pulmonary embolism (PE)	Up to postoperative day 4
Secondary	Systemic absorption of locally applied drug		Baseline (pre-surgery), immediately after administration of the topical agent, 1 hour after administration
Secondary	Patient assessed health-related quality of life score	This will be determined by a questionnaire/score	Up to 2 years postoperation
Secondary	Difference in costs for hospital stay between using tranexamic acid and placebo	Patient cost information will be gathered for the duration of the hospital stay	Duration of the hospital stay (an average of 2 weeks)