Professor Paul Myles (Monash University and Alfred Health)
Recruitment of the TRIGS trial has recommenced in November 2022, with 240 patients currently recruited. There will be six countries and more than 50 sites participating in the TRIGS Trial. The TRIGS -D trial and a cancer recurrence sub-study will be a sub-study of the main trial. We welcome new sites to join this trial.
A bolus of study drug, 0.15 ml/kg (TxA 15 mg/kg or matched placebo) before surgical incision, and then infusion at 0.05 ml/kg/h until the end of surgery. All other aspects of anaesthesia and surgery are flexible.
Surgical site infection.
Include red cell transfusion, other healthcare-associated infections (pneumonia, blood stream infection, etc), and the number of days at home within 30 days of surgery (DAH30).
Myocardial infarction, stroke and thromboembolic events; other adverse events. Entry criteria Adult patients scheduled for elective or semi-elective open or lap-assisted gastrointestinal surgery (oesophageal, gastric, hepatobiliary, pancreatic, colorectal) with one or more risk factors for complications.
The Australian National Health and Medical Research Council
ClinicalTrials.gov Identifier: NCT04192435
Robert Sanders, Lisbeth Evered, Mark Shulman, Wendy Brown, Stefan Dieleman, Tim McCulloch, Robert Medcalf and Jessica Kasza
Delirium is a devastating complication of medical and perioperative care, associated with increased morbidity and mortality, dementia and impaired long-term cognition, and loss of independence. Delirium is also associated with neuronal injury placing patients at risk for long-term changes in cognition. There are no proven therapies for postoperative delirium, mainly due to the lack of adequately powered, biologically plausible trials. There is growing evidence that tranexamic acid (TxA) may reduce inflammatory pathways in the central nervous system and protect the blood-brain barrier in trauma, and surgery.
TRIGS-D study aims
In a subset of 826 patients randomised in the TRIGS trial, we will collect data on delirium incidence and severity. Our specific aims are to investigate whether TxA:
- Aim 1: Reduces the incidence of postoperative delirium diagnosed with the 3D-CAM.
- Aim 2: Reduces the severity of delirium diagnosed with the 3D-CAM-Severity (3D-CAM-S).
- Aim 3: Modulates inflammatory (plasma cytokines, innate cell immune profile) and neurophysiological (EEG) responses in concert with any alteration in the incidence or severity of delirium.
- Aim 4: Reduces longer-term impairment of quality of life and improves disability-free survival.
Prophylactic TxA administration in patients undergoing major gastrointestinal surgery reduces the incidence of delirium after surgery when compared with placebo. The unifying hypothesis is that systemic and neuro-inflammation lead to neuronal injury and resultant postoperative delirium.
Multicentre, randomised, triple-blind, placebo-controlled, clinical trial (a substudy of the TRIGS trial). Patients are randomly assigned to either TxA or matched placebo. The incidence of postoperative delirium will be assessed daily using the 3D-CAM or CAM-ICU and medical record review for the first 3 days after surgery. In addition, follow up assessments will be done at 30 days and 12 months.
The Australian National Health and Medical Research Council project grant (ID 1185145) and the Australian and New Zealand College of Anaesthetists (22/002).
For further information about this study, please contact the TRIGS Project Manager, Sophie Wallace by email.