Tranexamic Acid to Reduce Delirium After Gastrointestinal Surgery: the TRIGS-D Trial

NCT ID: NCT05470816

Last Updated: 2025-12-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 826 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2026-08-31

Brief Summary

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.

Detailed Description

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.

This sub-study of the TRIGS trial (www.trigs.com.au) is evaluating the potential impact of TxA on the incidence and severity of delirium after surgery.

TRIGS-D Study Aims: In a subset of 826 patients enrolled in the TRIGS randomized trial data will be collected to identify delirium incidence and severity. The 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, randomized, triple-blind, placebo-controlled, clinical trial (a sub-study 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.

Conditions

Surgical Site Infection; Dementia; Cognition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Tranexamic Acid

12 mg/kg, before surgical incision, and then an infusion of 3 mg/kg/h until the end of surgery.

Group Type: ACTIVE_COMPARATOR

Tranexamic Acid 100Mg/ml Inj Vial 10ml

Intervention Type: DRUG

Intervention is from the Tranexamic acid to Reduce Infection after Gastrointestinal Surgery: the TRIGS Trial. A multicentre, pragmatic, double-blind, randomised clinical trial will compare the incidence of surgical site infection and red cell transfusion requirements after IV tranexamic acid and placebo in patients undergoing gastrointestinal surgery

Placebo

12 mg/kg, before surgical incision, and then an infusion of 3 mg/kg/h until the end of surgery.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline

Interventions

Tranexamic Acid 100Mg/ml Inj Vial 10ml

Intervention is from the Tranexamic acid to Reduce Infection after Gastrointestinal Surgery: the TRIGS Trial. A multicentre, pragmatic, double-blind, randomised clinical trial will compare the incidence of surgical site infection and red cell transfusion requirements after IV tranexamic acid and placebo in patients undergoing gastrointestinal surgery

Intervention Type: DRUG

Placebo

Normal saline

Intervention Type: DRUG

Other Intervention Names

Cyklokapron; Normal Saline

Eligibility Criteria

Inclusion Criteria

• Adult patients scheduled for elective gastrointestinal (oesophageal, gastric, hepatobiliary, colorectal) surgery
• with 2 or more risk factors for complications:
• age ≥70 years,
• American Society of Anesthesiologists (ASA) physical status 3 or 4,
• heart failure, diabetes,
• chronic respiratory disease,
• obesity (BMI ≥30 kg/m2),
• vascular disease,
• preoperative haemoglobin <100 g/L,
• renal impairment (se. creatinine ≥150 micromol/L), or low albumin (<30 g/L).

Exclusion Criteria

• Poor spoken and/or written language comprehension,
• laparoscopic and other minor (eg. closure of stoma) surgery,
• pre-existing infection/sepsis,
• history of spontaneous pulmonary embolism or arterial thrombosis,
• current arterial or venous thrombosis,
• familial thrombophilia (e.g. Lupus anticoagulant, protein C deficiency, factor V Leiden),
• contraindication to TxA.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Monash University

OTHER

Sponsor Role: collaborator

Bayside Health

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul S Myles, DSci

Role: STUDY_CHAIR

Monash University

Locations

Alfred Health

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

58/20

Identifier Type: -

Identifier Source: org_study_id