A Trial of a Hospital Policy of Tranexamic Acid Use to Reduce Transfusion in Major Non-cardiac Surgery

Study Overview
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Brief Summary
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A Phase IV trial of a hospital policy of Tranexamic acid to reduce transfusion in major non-cardiac surgery.

Detailed Description
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The TRACTION Trial is a national multi-centre Phase IV randomized cluster-crossover trial of Tranexamic acid versus placebo. Over the duration of the study, participating centres will be centrally and randomly allocated to receive either TXA or matching placebo at 1-month intervals for a total of 8 months. As our pragmatic trial is designed to define practice, we have selected co-primary outcomes that evaluate effectiveness in the context of safety. Our co-primary outcomes are the: Proportion of patients transfused RBCs Incidence of DVT or PE (collectively called venous thromboembolism (VTE) within 3 months of surgery.

Official Title
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A Phase IV Trial of a Hospital Policy of Tranexamic Acid Use to Reduce Transfusion in Major Non-cardiac Surgery (TRACTION): A Pragmatic Randomized Cluster Crossover Trial

Conditions
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Major Non-cardiac Surgeries

Intervention / Treatment
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* Drug: Tranexamic acid (TXA)
* Drug: Placebo (0.9 % Saline)


Participation Criteria
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Eligibility Criteria
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Cluster-level inclusion criteria: Hospital sites will be included in the trial if anesthesia and hospital leadership agree to manage patients as per the policy being implemented and evaluated in the trial. Patient-level inclusion criteria: Patients >/= 18 years of age undergoing major non-cardiac surgery (a state of hyperfibrinolysis) Inpatient surgeries with an estimated >/= 5% risk of RBC transfusion, including open surgeries or laparoscopic surgeries with an estimated duration of >/= 3 hours Examples of eligible surgeries could include (but are not limited to): General surgery (esophagectomy, gastrectomy, gastric repair, small bowel repair or resection, ostomy formation, colon/rectum repair or resection, colostomy, splenectomy, hepatectomy, pancreatectomy, resection of abdominal mass) Orthopedics (hip fracture repair, pelvic fixation, femur repair / fixation, shoulder / humerus open reduction internal fixation, lower extremity amputation) Spine (vertebrectomy, surgery involving >/= 3 levels) Otolaryngology (glossectomy, mandibulectomy, radical laryngectomy) Thoracic (lung resection or decortication) Vascular (arterial bypass / endarterectomy / aneurysmorrhaphy involving the aorta or proximal vessels off the aorta) Gynecology (hysterectomy) Urology (nephrectomy, cystectomy, prostatectomy, pelvic exenteration) Plastic surgery (large neoplasm resections, burns or debridements) Surgeries anticipated to be associated with 5% or greater risk of RBC transfusion in hospital as per the surgical team. Exclusion Criteria: Active thromboembolic disease (ie, patient is anticoagulated for thromboembolic disease prior to admission) Pregnancy Cardiac surgery and hip and knee arthroplasty where TXA is standard-of-care Surgeries with free flap reconstruction Trauma surgeries where TXA was administered within the previous 3 hours.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: TRACTION is a pragmatic, multicenter, randomized, registry-based cluster-crossover trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tranexamic acid (TXAl Arm<br>TXA 1 gram bolus (2 grams for patients over 100 kg) intravenously (IV) administered within 10 minutes of the first surgical incision, followed by 1 additional gram given intravenously at 2-4 hours of surgery or prior to skin closure, at the discretion of the anesthesiologist (e.g. IV bolus at 2-4 hours of surgery, at skin closure, or the 1 additional gram given as a continuous infusion throughout the surgical procedure). | Drug: Tranexamic acid (TXA)<br>* TXA 1 gram bolus (2 grams for patients over 100 kg) intravenously (IV) administered within 10 minutes of the first surgical incision, followed by 1 additional gram given intravenously at 2-4 hours of surgery or prior to skin closure, at the discretion of the anesthesiologist (e.g. IV bolus at 2-4 hours of surgery, at skin closure, or the 1 additional gram given as a continuous infusion throughout the surgical procedure).<br>|
| Placebo Comparator: Placebo Arm<br>Placebo 1 gram bolus (2 grams for patients over 100 kg) intravenously (IV) administered within 10 minutes of the first surgical incision, followed by 1 additional gram given intravenously at 2-4 hours of surgery or prior to skin closure, at the discretion of the anesthesiologist (e.g. IV bolus at 2-4 hours of surgery, at skin closure, or the 1 additional gram given as a continuous infusion throughout the surgical procedure). | Drug: Placebo (0.9 % Saline)<br>* Placebo (0.9 % normal saline) 1 gram bolus (2 grams for patients over 100 kg) intravenously (IV) administered within 10 minutes of the first surgical incision, followed by 1 additional gram given intravenously at 2-4 hours of surgery or prior to skin closure, at the discretion of the anesthesiologist (e.g. IV bolus at 2-4 hours of surgery, at skin closure, or the 1 additional gram given as a continuous infusion throughout the surgical procedure).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of RBC Transfusions | Number of patients requiring transfused RBCs. | Randomization through hospital discharge, anticipated less than 7 days. | 
| Incidence of DVT or PE (collectively called venous thromboembolism (VTE) | Number of patients with VTE events | Within 3 months of surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfused units | The number of RBC units transfused (both at cluster level and patient level). | Randomization through hospital discharge, anticipated less than 7 days. | 
| Arterial or Venous thrombotic events | Secondary safety outcomes include the in-hospital diagnosis of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolus. | Randomization through hospital discharge, anticipated less than 7 days. | 
| Clinical | Hospital length of stay | During hospital stay up to 90 days | 
| Clinical | Number of participants requiring ICU admission | During hospital stay up to 90 days | 
| Clinical | 3-month survival | During hospital stay up to 90 days | 
| the number of days at home to day 30 (DAH30) | the number of days at home to day 30 (DAH30) | up to day 30 | 
| Compliance | Proportion of eligible patients who receive the policy intervention, and the policy compliance | Randomization through hospital discharge, anticipated less than 7 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tranexamic acid (TXA), Venous thromboembolism (VTE), Deep vein thrombosis (DVT), Transfusion, Perioperative Bleeding