Tranexamic acid to reduce Delirium after Gastrointestinal Surgery:
the TRIGS-D trial sub-study of the TRIGS trial

Principal Investigator

Paul Myles

Co-Investigators

Robert Sanders, Lisbeth Evered, Mark Shulman, Wendy Brown, Stefan Dieleman, Tim McCulloch, Robert Medcalf & Jessica Kasza

Trial Summary

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 enrolled in the TRIGS randomised 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.

Primary Hypothesis

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.

Study Design

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.

Funding Source

The Australian National Health and Medical Research Council project grant (ID 1185145) and the Australian and New Zealand College of Anaesthetists (22/002)