Tranexamic Acid in Reducing Gross Hemorrhage and Transfusions of Spine Surgeries (TARGETS)

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

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.

Study Overview

• Status: Unknown
• Conditions: Intervertebral Disc Displacement; Spinal Stenosis
• Intervention / Treatment: Drug: Wound topically irrigated with 500mg TXA; Drug: 1mg/kg/hr TXA intravenous infusion till the last suture

• Study Type: Interventional
• Enrollment (Anticipated): 176
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; 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
Other: Control; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Hui S, Tao L, Mahmood F, Xu D, Ren Z, Chen X, Sheng L, Zhuang Q, Li S, Huang Y. Tranexamic Acid in Reducing Gross Hemorrhage and Transfusions of Spine Surgeries (TARGETS): study protocol for a prospective, randomized, double-blind, non-inferiority trial. Trials. 2019 Feb 12;20(1):125. doi: 10.1186/s13063-019-3231-9.

Study record dates

Study Major Dates

• Study Start: February 1, 2017
• Primary Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: December 16, 2016
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (Estimate): January 5, 2017

Study Record Updates

• Last Update Posted (Estimate): January 5, 2017
• Last Update Submitted That Met QC Criteria: January 4, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Musculoskeletal Diseases; Pathological Conditions, Anatomical; Spinal Diseases; Bone Diseases; Hernia; Hemorrhage; Intervertebral Disc Displacement; Spinal Stenosis
• Other Study ID Numbers: PUMCH-000391