Tranexamic Acid in Reducing Gross Hemorrhage and Transfusions of Spine Surgeries

Study Overview
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Brief Summary
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Multilevel decompression and bone graft fusion is a most effective measure for treating degenerative lumbar spinal diseases. Yet, the surgery is commonly associated with large amount of perioperative blood loss and high demand for homologous blood transfusion. Tranexamic acid (TXA) has been proved as efficient in reducing the gross blood loss in various kinds of surgeries. However, high quality evidence of its efficacy and safety is still lacking in lumbar spinal surgeries. Besides, systemic use of TXA carries the risks of thromboembolic complications such as deep venous thrombosis and pulmonary embolism, thus the optimal drug delivery route of TXA remains undetermined. The aim of this study is to test the non-inferiority of topical TXA application to its intravenous use in multilevel decompression and bone graft fusion surgeries. A prospective, randomized, double-blind, head-to-head comparison study design will be adopted.

Official Title
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Intravenous Versus Topical Use of Tranexamic Acid in Reducing Gross Hemorrhage and Transfusions of Spine Surgeries (TARGETS) : A Prospective, Randomized, Double Blind, Head-to-head Comparison Study

Conditions
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Spinal Stenosis, Intervertebral Disc Displacement

Intervention / Treatment
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* Drug: Wound topically irrigated with 500mg TXA
* Drug: 1mg/kg/hr TXA intravenous infusion till the last suture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists(ASA)classification of physical status I-II. Aged over 50yrs. Patients suffering from spinal stenosis or intervertebral disc displacement and require multilevel decompression and bone graft fusion surgeries. Written informed consent. Exclusion Criteria: ASA III-IV. Age≤ 50yrs. History of chronic renal dysfunction (preoperative blood creatinine> 120mmol/L), liver dysfunction (preoperative blood aspartate or alanine aminotransferase> 50 units/L) or history of coronary artery disease with stent placement. Abnormal preoperative coagulation profile (preoperative prothrombin time elongation> 3s, activated partial thromboplastin time elongation> 10s, platelet counts< 100*10^9/L or >400*10^9/L, or INR> 1.4). Pre-existing anemia (male< 12g/dL, female<11g/dL). Long-term medications of aspirin and/or other anticoagulants. Patients known as allergic to TXA. Patients who have religious and/or other beliefs limiting blood transfusion. Dura mater laceration and/or unexpected massive bleeding during operation. Cell saver application during operation.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Loading dose: 100ml 0.9% normal saline(NS) intravenous infusion, 15-20min prior to operation initiation. Maintenance dose: 5ml/hr 0.9% NS intravenous infusion till the last suture. Bolus dose: the wound topically irrigated with 500mg TXA in 250ml 0.9% NS for 5min. Waste fluid was then removed by suction, and the wound was closed. | Drug: Wound topically irrigated with 500mg TXA<br> <br> |
| Other: Control<br>Loading dose: 10mg/kg tranexamic acid(TXA) in 100ml 0.9% NS intravenous infusion, 15-20min prior to operation initiation. Maintenance dose: 1mg/kg/hr TXA intravenous infusion till the last suture. Bolus dose: the wound topically irrigated with 250ml 0.9% NS for 5min. Waste fluid was then removed by suction, and the wound was closed. | Drug: 1mg/kg/hr TXA intravenous infusion till the last suture<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative Total blood loss (TBL) | TBL= PBV*（hematocrit on postoperative day 3- preoperative hematocrit）/average hematocrit; Predicted blood volume(PBV)= k1* height^3(m)+ k2* weight(kg)+ k3 (female: k1=0.3561， k2=0.03308， k3=0.1833, male: k1=0.3669， k2=0.03219， k3=0.6041) | Since operation initiation till postoperative day 3 (POD3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visible intraoperative blood loss |  | Since operation initiation till operation completion, an average of 120min | 
| Visible postoperative blood loss within 24hrs |  | 0- 24hrs postoperatively | 
| Visible postoperative blood loss within 48hrs |  | 0- 48hrs postoperatively | 
| Combined visible perioperative blood loss | Combined visible perioperative blood loss= visible intraoperative blood loss + visible postoperative blood loss within 24hrs + visible postoperative blood loss within 48hrs | Since operation initiation till postoperative 48hrs | 
| Total postoperative blood loss | Total postoperative blood loss= drainage day1(ml)* drainage Hct day1(%)/blood Hct day1(%)+ drainage day2(ml)* drainage Hct day2(%)/blood Hct day2(%) | 0- 48hrs postoperatively | 
| Postoperative hidden blood loss (HBL) | HBL=TBL- combined visible perioperative blood loss | 48hrs postoperatively | 
| Postoperative prothrombin time(PT) |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs | 
| Postoperative activated partial thromboplastin time(APTT) |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs | 
| Postoperative fibrinogen level(Fbg) |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs | 
| Postoperative international normalized ratio(INR) |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs | 
| Postoperative R time |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs, using thromboelastography tests. | 
| Postoperative K time |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs, using thromboelastography tests. | 
| Postoperative maximum amplitude (MA) |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs, using thromboelastography tests. | 
| Postoperative lysis after 30 minutes(LY 30) |  | Tested at operation completion, postoperative 24hrs and postoperative 48hrs, using thromboelastography tests. | 
| Postoperative hemoglobin nadir |  | Since operation completion till postoperative 48hrs | 
| Perioperative transfusion rates |  | Since operation initiation till postoperative 48hrs | 
| Perioperative transfusion amounts |  | Since operation initiation till postoperative 48hrs | 
| Length of hospital stay | Length of hospital stay is calculated by subtracting day of admission from day of discharge. | A single inpatient duration since the day of admission till the day of discharge, an average of 1 week | 
| Adverse event rates | Adverse events include deep venous thrombosis, myocardial infarction, pulmonary embolism, cerebrovascular disease, impaired liver function, impaired renal function and incisional hematoma/ infection. | Since operation initiation till postoperative 48hrs |