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

Bayside Health

Status and phase: Enrolling; Phase 3

Conditions: Surgical Site Infection; Cognition; Dementia

Treatments: Drug: Tranexamic Acid 100Mg/ml Inj Vial 10ml; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05470816

58/20

Details and patient eligibility

About

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.

Full 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.

Enrollment: 826 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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826 participants in 2 patient groups, including a placebo group

Tranexamic Acid

Active Comparator group

Description:

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

Treatment:

Drug: Tranexamic Acid 100Mg/ml Inj Vial 10ml

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo