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NCT Number: NCT06361238

Liraglutide in Preventing Delirium in Diabetic Elderly After Cardiac Surgery

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.

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Key information

Age range

60 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 60 years
  • Type 2 diabetes
  • Patients undergoing elective cardiac surgery

Exclusion criteria

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

Treatment and study plan

Liraglutide injection

Drug

Subcutaneous injection of liraglutide: 0.6 mg administered the day before surgery, 1.8 mg administered post-anesthesia induction on the day of surgery, followed by 0.6 mg daily for the first three postoperative days.

Other names: Victoza

Placebo injection

Drug

Subcutaneous injection of Placebo: the same volume as liraglutide administrated at the corresponding times.

Other names: Normal saline

Primary outcomes

  1. The incidence of delirium

    Time frame: One day before surgery and within the first seven days after surgery.

    Confusion Assessment Method (CAM), or its variant for the Intensive Care Unit, known as CAM-ICU, is the tool used to assess the incidence of delirium. For CAM, the scale ranges from a minimum value of 11 to a maximum of 44, with higher scores indicating a worse outcome. In contrast, CAM-ICU does not utilize a numerical scale; it is a qualitative assessment designed to evaluate confusion without assigning specific values.

Secondary outcomes

  1. The severity of delirium

    Time frame: One day before surgery and within the first seven days after surgery.

    The CAM-Severity Scale (CAM-S), available in both short-form and long-form versions, serves as a tool for assessing the severity of delirium. The scale extends from 0 to 7 in its short-form and from 0 to 19 in its long-form. Higher scores on the CAM-S are indicative of more severe outcomes.

  2. Cognitive function

    Time frame: One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    Minimum Mental State Examination (MMSE) is the tool used to assess cognitive function. The scale extends from 0 to 30, with higher scores indicating a better outcome.

  3. Anxiety

    Time frame: One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    Generalized anxiety disorder-7 (GAD-7) is the tool used to assess anxiety. The scale extends from 0 to 21, with higher scores indicating a worse outcome.

  4. Depression

    Time frame: One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    Patient Health Questionnaire-9 (PHQ-9) is the tool used to assess depression. The scale extends from 0 to 27, with higher scores indicating a worse outcome.

  5. Duration of ICU stay

    Time frame: The time from transfer into the ICU to discharge from the ICU, assessed up to 12months.

    By retrieving the Hospital Information System and ICU special care sheet

  6. Mechanical ventilation time

    Time frame: The time from tracheal intubation to the removal of the tracheal tube, assessed up to 12months.

    By retrieving the Hospital Information System and ICU special care sheet

  7. Duration of hospital stay

    Time frame: The time from hospital admission to discharge, assessed up to 12months.

    By retrieving the Hospital Information System

  8. In-hospital mortality

    Time frame: The time from hospital admission to discharge, assessed up to 12months.

    By retrieving the Hospital Information System

  9. Incidence of adverse events

    Time frame: One day preoperatively to three days Postoperatively.

    By retrieving the Hospital Information System, ICU special care sheet and follow-up

  10. Rate of major cardiovascular adverse events

    Time frame: Within 1 year post-surgery (including cardiovascular death, myocardial infarction, and stroke)

    By retrieving the Hospital Information System, ICU special care sheet and follow-up

  11. Serum levels of NSE

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  12. Serum levels of CRP

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  13. Serum levels of IL-1α

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  14. Serum levels of TNF-α

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  15. Serum levels of C3

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  16. Serum levels of LDH

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  17. Serum levels of CK

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  18. Serum levels of CK-MB

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  19. Serum levels of AST

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  20. Serum levels of cTNT

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  21. Serum levels of BNP

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  22. Serum levels of C1q

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  23. Serum levels of IL-1β

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  24. Serum levels of IL-6

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  25. Serum levels of S100β

    Time frame: One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively

    ELISA

  26. Left Ventricular Posterior Wall Thickness in Diastole (LVPWTd)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the LVPWTd.

  27. Left Ventricular End-Diastolic Dimension (LVDd)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the LVDd.

  28. Left Ventricular End-Systolic Diameter (LVDs)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the LVDs.

  29. Left Atrial Diameter (LAD)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the LAD.

  30. Ejection Fraction (EF)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the EF.

  31. Fractional Shortening (FS)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the FS.

  32. Early Diastolic Velocity/Atrial Diastolic Velocity (E/A)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the E/A.

  33. Interventricular Septum Thickness in Diastolic (IVSTd)

    Time frame: One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

    The echocardiography is used to assess the IVSTd.

Study contacts

Contact information is provided by the study sponsor or research team.

Wenxue Liu, PhD,MD

CONTACT

[email protected]

15751866806

Sponsors and collaborators

Lead sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Other

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Apr 11, 2024
Registry last updated
Dec 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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