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

Phase 3Active Not RecruitingNCT05470816

Bayside Health826 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

826

Conditions

Surgical Site Infection Dementia Cognition

Interventions

Tranexamic Acid 100Mg/ml Inj Vial 10mlDRUG

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

PlaceboDRUG

Normal saline

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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). * Written informed consent will be obtained. 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.

Locations (1)

Alfred Health

Melbourne, Victoria, Australia

Outcomes

Primary Outcomes

incidence of delirium in the first 3 days postoperatively

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

Time frame: post surgical incision to day 3 (at anytime)obtaining information from the patient, family and staff, and thorough chart review

Secondary Outcomes

Delirium severity

3D-CAM-S

Time frame: post surgical incision to day 3 (inclusive)

Quality of Life Intergroup differences

using the Short form survey 12 - Quality of Life Intergroup differences in long-term (12 month) in perioperative cognitive decline

Time frame: 12 months post surgical incision

Disability

World Health Organization disability assessment schedule. Intergroup differences in long-term (12 month) in perioperative cognitive decline

Time frame: 12 months post surgical incision

perioperative neurocognitive disorders (NCDs)

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).

Time frame: 12 months post surgical incision

Days at home up to 30 days after surgery (DAH30)

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).

Time frame: 30 days post surgical incision post surgical incision

Data from ClinicalTrials.gov

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