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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- The incidence of delirium
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 60 years
- •Type 2 diabetes
- •Patients undergoing elective cardiac surgery
排除标准
- •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
研究组 & 干预措施
Liraglutide Group
Subcutaneous injection of liraglutide
干预措施: Liraglutide injection (Drug)
Vehicle Group
Subcutaneous injection of vehicle
干预措施: Placebo injection (Drug)
结局指标
主要结局
The incidence of delirium
时间窗: 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.
次要结局
- The severity of delirium(One day before surgery and within the first seven days after surgery.)
- Duration of ICU stay(The time from transfer into the ICU to discharge from the ICU, assessed up to 12months.)
- Mechanical ventilation time(The time from tracheal intubation to the removal of the tracheal tube, assessed up to 12months.)
- Duration of hospital stay(The time from hospital admission to discharge, assessed up to 12months.)
- Cognitive function(One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Anxiety(One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Depression(One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- In-hospital mortality(The time from hospital admission to discharge, assessed up to 12months.)
- Incidence of adverse events(One day preoperatively to three days Postoperatively.)
- Rate of major cardiovascular adverse events(Within 1 year post-surgery (including cardiovascular death, myocardial infarction, and stroke))
- Serum levels of NSE(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of CRP(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of IL-1α(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of TNF-α(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of BNP(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of C3(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of LDH(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of CK(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of CK-MB(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of AST(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of cTNT(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of C1q(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Left Ventricular End-Diastolic Dimension (LVDd)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Left Ventricular End-Systolic Diameter (LVDs)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Early Diastolic Velocity/Atrial Diastolic Velocity (E/A)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Serum levels of IL-1β(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of IL-6(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Serum levels of S100β(One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively)
- Left Ventricular Posterior Wall Thickness in Diastole (LVPWTd)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Left Atrial Diameter (LAD)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Ejection Fraction (EF)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Fractional Shortening (FS)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)
- Interventricular Septum Thickness in Diastolic (IVSTd)(One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.)