Tranexamic Acid to Reduce Blood Loss in Spine Trauma Surgery

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

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.

Study Overview

• Status: Recruiting
• Conditions: Spinal Injuries; Spinal Deformity
• Intervention / Treatment: Drug: Tranexamic Acid; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 252
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ronald A Lehman, MD; Phone Number: 2129325067; Email: rl2781@cumc.columbia.edu
• Study Contact Backup: Name: Matthew J. Cooney; Email: mc5386@cumc.columbia.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94149
      • Not yet recruiting
      • University of California San Francisco Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Not yet recruiting
      • Norton Leatherman Spine Center
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • NYP/The Allen Hospital - CUIMC
      • Contact: Ronald A. Lehman, MD; Email: rl2781@cumc.columbia.edu
      • Principal Investigator: Ronald A. Lehman, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Not yet recruiting
      • Duke University Medical Center
  • Washington
    • Tacoma, Washington, United States, 98431
      • Not yet recruiting
      • Madigan Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; Subjects will receive tranexamic acid on the surgical wound.	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.; Other Names: TXA; Cyclokapron
Placebo Comparator: Placebo control; Subjects will receive placebo (saline solution) on the surgical wound.	Drug: 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.; Other Names: Saline Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximal drop in systemic hemoglobin concentration during the postoperative period	Patients will be followed through postoperative day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Number of complications	Defined as thromboembolic event, including deep vein thrombosis (DVT) or pulmonary embolism (PE)	Up to postoperative day 4
Systemic absorption of locally applied drug		Baseline (pre-surgery), immediately after administration of the topical agent, 1 hour after administration
Patient assessed health-related quality of life score	This will be determined by a questionnaire/score	Up to 2 years postoperation
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)

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Ronald A Lehman, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: December 3, 2014
• First Submitted That Met QC Criteria: December 8, 2014
• First Posted (Estimated): December 11, 2014

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Tranexamic acid; Antifibrinolytic; Perioperative blood loss; Postoperative drain output; Allogenic transfusion
• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Back Injuries; Hemorrhage; Spinal Injuries; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: AAAQ6795; 201409111 (Other Identifier: Washington University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No