Clinical trial NCT06361238: Liraglutide in Preventing Delirium in Diabetic Elderly After Cardiac Surgery
Official title: Perioperative Application of Liraglutide for the Prevention of Postoperative Delirium Among Elderly Patients with Type 2 Diabetes Undergoing Cardiac Surgery: a Single-Center Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Delirium, Postoperative
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2024-04-11
Enrollment: 260
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to clarify the preventive effect of perioperative liraglutide application on postoperative delirium in elderly patients with Type 2 diabetes undergoing cardiac surgery.

Detailed description: Delirium is the most prevalent neurological complication following cardiac surgery. It is characterized by an acute and fluctuating disturbance in consciousness, attention, and cognitive function. The incidence of delirium post-cardiac surgery ranges between 11% and 46%. It is closely linked to increased postoperative mortality, extended hospital stays, higher healthcare costs, and long-term cognitive impairment. Currently, it is widely recognized that the development of delirium is influenced by multiple factors, including advanced age, diabetes, surgical and anesthetic techniques, depression, baseline cognitive function, and infections, among others.

Inflammatory responses, crucial for protecting against external or internal threats, can, following surgery, lead to neuroinflammation and neurological damage due to elevated postoperative inflammatory markers and blood-brain barrier disruption. The involvement of microglia and astrocytes, key players in the central nervous system's immune response, has been identified in mediating postoperative delirium, making them potential targets for prevention.

Liraglutide, a Glucagon-like peptide-1 receptor agonist primarily used for treating Type 2 diabetes, has shown promise in mitigating neurocognitive damage associated with diabetes and Alzheimer's disease, suggesting its potential in preventing postoperative delirium in cardiac surgery patients with Type 2 diabetes. Preliminary animal studies and a randomized controlled trial indicate that perioperative liraglutide application could reduce the incidence of postoperative delirium by inhibiting glial activation and the subsequent neuroinflammatory response. However, differences in patient demographics, disease severity, and dosing in previous studies highlight the need for further investigation.

The study aims to investigate whether the perioperative administration of liraglutide can prevent the onset of postoperative delirium in elderly patients with Type 2 diabetes undergoing cardiac surgery. Secondary objectives include assessing the impact on the severity and duration of delirium, cognitive function, anxiety, depression, cardiac function, cardiovascular events, ICU stay, mechanical ventilation duration, and levels of serum markers for brain injury, inflammation, myocardial damage, and cardiac function.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 60 years
2. Type 2 diabetes
3. Patients undergoing elective cardiac surgery

Exclusion Criteria:

1. History of neurological or psychiatric disorders, such as schizophrenia, epilepsy, Parkinson's disease, severe dementia, etc
2. Patients with communication difficulties, such as severe visual, auditory, or speech impairments
3. History of central nervous system damage or surgery
4. Cardiac function NYHA Class IV
5. Severe liver dysfunction (Child-Pugh Class C)
6. Severe renal failure requiring renal replacement therapy
7. History of pancreatitis
8. Type 1 diabetes
9. Patients whose blood sugar is difficult to control within 4-8 mmol/L during the screening period
10. Patients with medullary thyroid carcinoma or a family history of it
11. Pregnant or breastfeeding women
12. Intolerance or allergy to liraglutide
13. Previous use of GLP-1A and SGLT2i
14. Patients who refuse to sign the informed consent

Primary outcomes:
measure: The incidence of delirium
timeFrame: One day before surgery and within the first seven days after surgery.
Secondary outcomes:
measure: The severity of delirium
timeFrame: One day before surgery and within the first seven days after surgery.
measure: Cognitive function
timeFrame: One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Anxiety
timeFrame: One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Depression
timeFrame: One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Duration of ICU stay
timeFrame: The time from transfer into the ICU to discharge from the ICU, assessed up to 12months.
measure: Mechanical ventilation time
timeFrame: The time from tracheal intubation to the removal of the tracheal tube, assessed up to 12months.
measure: Duration of hospital stay
timeFrame: The time from hospital admission to discharge, assessed up to 12months.
measure: In-hospital mortality
timeFrame: The time from hospital admission to discharge, assessed up to 12months.
measure: Incidence of adverse events
timeFrame: One day preoperatively to three days Postoperatively.
measure: Rate of major cardiovascular adverse events
timeFrame: Within 1 year post-surgery (including cardiovascular death, myocardial infarction, and stroke)
measure: Serum levels of NSE
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of CRP
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of IL-1α
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of TNF-α
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of C3
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of LDH
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of CK
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of CK-MB
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of AST
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of cTNT
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of BNP
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of C1q
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of IL-1β
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of IL-6
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Serum levels of S100β
timeFrame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
measure: Left Ventricular Posterior Wall Thickness in Diastole (LVPWTd)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Left Ventricular End-Diastolic Dimension (LVDd)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Left Ventricular End-Systolic Diameter (LVDs)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Left Atrial Diameter (LAD)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Ejection Fraction (EF)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Fractional Shortening (FS)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Early Diastolic Velocity/Atrial Diastolic Velocity (E/A)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
measure: Interventricular Septum Thickness in Diastolic (IVSTd)
timeFrame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Wenxue liu
state: Jiangsu
Study officials:
affiliation: Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University
name: Dongjin Wang, PhD，MD
role: PRINCIPAL_INVESTIGATOR
References: