Clinical trial NCT05470816: Tranexamic Acid to Reduce Delirium After Gastrointestinal Surgery: the TRIGS-D Trial
Official title: Tranexamic Acid to Reduce Delirium After Gastrointestinal Surgery: the TRIGS-D Trial (a Substudy of the TRIGS Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Surgical Site Infection
Dementia
Cognition
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
Collaborators: name: Monash University
First posted: 2022-07-22
Enrollment: 826
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, randomised, triple-blind, placebo-controlled, clinical trial (a substudy of the TRIGS trial).
Primary purpose: PREVENTION

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.

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).
* 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.

Primary outcomes:
measure: incidence of delirium in the first 3 days postoperatively
timeFrame: post surgical incision to day 3 (at anytime)obtaining information from the patient, family and staff, and thorough chart review
Secondary outcomes:
measure: Delirium severity
timeFrame: post surgical incision to day 3 (inclusive)
measure: Quality of Life Intergroup differences
timeFrame: 12 months post surgical incision
measure: Disability
timeFrame: 12 months post surgical incision
measure: perioperative neurocognitive disorders (NCDs)
timeFrame: 12 months post surgical incision
measure: Days at home up to 30 days after surgery (DAH30)
timeFrame: 30 days post surgical incision post surgical incision
measure: cytokine levels
timeFrame: preoperative, postoperative day 1 and 3 post surgical incision
measure: neuronal injury biomarker
timeFrame: preoperative, postoperative day 1 and 3 post surgical incision
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
Study officials:
affiliation: Monash University
name: Paul S Myles, DSci
role: STUDY_CHAIR
References: