Tranexamic Acid to Reduce Infection After Gastrointestinal Surgery

Study Overview
=================
Brief Summary
-----------------
This international, multicentre, pragmatic, double-blind, placebo-controlled, randomised trial of TxA versus placebo will enrol 3,300 patients throughout Australia and internationally. This is an effectiveness trial - some elements of the trial are deliberately left to the perioperative clinicians' discretion in order to reflect usual practice and maximise generalisability.

Detailed Description
-----------------
Study Aims: To conduct a large, multicentre clinical trial of tranexamic acid (TxA), an antifibrinolytic drug routinely used to reduce bleeding in cardiac and some orthopaedic surgery, in 3,300 patients undergoing major gastrointestinal (GI) surgery. Our specific aims are to investigate whether TxA: Aim 1: Reduces surgical site infection (wound infection), and other healthcare-associated infections (pneumonia and sepsis). Aim 2: Reduces red cell transfusion in GI surgery. Aim 3: Reduces a pooled composite of any serious postoperative complications, and so increases days alive and at home up to 30 days after surgery (DAH30). Aim 4: To evaluate the temporal effect of TxA on perioperative immune and inflammatory responses. Study Hypothesis Prophylactic TxA administration in patients undergoing major GI surgery reduces the incidence of surgical site infection (SSI) after surgery when compared with placebo.

Official Title
-----------------
Tranexamic Acid to Reduce Infection After Gastrointestinal Surgery; The TRIGS Trial

Conditions
-----------------
Infection Wound, Gastrointestinal Complication, Anesthesia, Bleeding, Healthcare Associated Infection

Intervention / Treatment
-----------------
* Drug: Tranexamic Acid
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Adult patients scheduled for elective or semi-elective (inpatient) open or lap-assisted GI surgery (oesophageal, gastric, hepatobiliary, colorectal) with one or more risk factors for complications: Age ≥70 years ASA physical status 3 or 4 Known or suspected history of: heart failure, diabetes, peripheral vascular disease, or chronic respiratory disease Obesity (BMI ≥30 kg/m2) Anaemia (preoperative haemoglobin <130 g/l in males and <120 g/l in females) Renal impairment (se. creatinine ≥150mol/l) Low albumin (<30 g/L) Exclusion Criteria: Poor spoken and or written language comprehension Laparoscopic cholecystectomy and other minor (eg. closure of stoma) surgery Pre-existing infection/sepsis Known history of: spontaneous pulmonary embolism, arterial thrombosis familial thrombophilia (e.g. Lupus anticoagulant, protein C deficiency, factor V Leiden)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blind, placebo-controlled, randomised trial of TxA versus placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tranexamic acid<br>At induction of anesthesia and prior to surgical incision a bolus of 0.15 ml/kg ( up to a maximum of 15 ml) , and then commence an infusion of 0.05 ml/kg/h until the end of surgery. The total maximal administered study drug volume will be 30 ml. | Drug: Tranexamic Acid<br>* 100mg/ml<br>|
| Placebo Comparator: Placebo<br>At induction of anesthesia and prior to surgical incision a bolus of 0.15 ml/kg ( up to a maximum of 15 ml) , and then commence an infusion of 0.05 ml/kg/h until the end of surgery. The total maximal administered study drug volume will be 30 ml. | Drug: Placebos<br>* Placebo will be 5ml vials calculated to equivalent to the 100mg/ml of active drug.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Surgical Site Infection | defined by the US Centers for Disease Control (CDC) | from surgical incision to 30 days post surgical incision | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red cell transfusion | Total units given | from surgical incision to hospital discharge (from index surgery) or 30 days. | 
| Other healthcare-associated infections | sepsis, pneumonia, blood stream infection, UTI, etc; all using CDC-guided definitions | from surgical incision to 30 days | 
| C-reactive protein | peak | Postoperative Day 3 (three days after surgical incision) | 
| Days at home up to 30 days after surgery (DAH30). | Time that patient spends at home in the 30 days following surgery | From surgical incision to 30 days |