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

Phase 3

Recruiting

• Conditions: Surgical Site Infection; Dementia; Cognition
• Interventions: Drug: Placebo; Drug: Tranexamic Acid 100Mg/ml Inj Vial 10ml

• Registration Number: NCT05470816
• Lead Sponsor: Bayside Health

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.

Study Timeline

• Study First Submitted: 2022-07-05
• Study First Submitted QC: 2022-07-20
• Study First Posted: 2022-07-22
• Study Start: 2022-11-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-12
• Primary Completion: 2025-12-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 826

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	12 mg/kg, before surgical incision, and then an infusion of 3 mg/kg/h until the end of surgery.
Tranexamic Acid	Tranexamic Acid 100Mg/ml Inj Vial 10ml	12 mg/kg, before surgical incision, and then an infusion of 3 mg/kg/h until the end of surgery.

Primary Outcome Measures

Name	Time	Method
incidence of delirium in the first 3 days postoperatively	post surgical incision to day 3 (at anytime)obtaining information from the patient, family and staff, and thorough chart review	3D-Confusion Assessment Method (3D-CAM) or CAM-ICU if the Used to measure delirium. Assessments will be conducted twice daily A classification of delirium will be made if both features 1 and 2 are present

Secondary Outcome Measures

Name	Time	Method
perioperative neurocognitive disorders (NCDs)	12 months post surgical incision	NCD will be defined as any of: (i) subjective complaint, (ii) a 4-point reduction in TICS-B, (iii) SF or VF, and (iv) functional deficit defined as a reduction in WHODAS score of 5% or more from baseline (before surgery).
Delirium severity	post surgical incision to day 3 (inclusive)	3D-CAM-S
Quality of Life Intergroup differences	12 months post surgical incision	using the Short form survey 12 - Quality of Life Intergroup differences in long-term (12 month) in perioperative cognitive decline
Disability	12 months post surgical incision	World Health Organization disability assessment schedule. Intergroup differences in long-term (12 month) in perioperative cognitive decline
Days at home up to 30 days after surgery (DAH30)	30 days post surgical incision post surgical incision	DAH30 is patient-centred and reflects the patient's primary aim of a healthy recovery, reduced hospital costs and serious complications, and avoiding re-admission (often due to postoperative delirium).
cytokine levels	preoperative, postoperative day 1 and 3 post surgical incision	Blood tests measured in 92 key inflammatory/immune markers using technology
neuronal injury biomarker	preoperative, postoperative day 1 and 3 post surgical incision	used to evaluate temporal changes in the innate cellular immune and inflammatory profile, and for changes in fibrinolysis

Trial Locations

Locations (1)

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia