Clinical trial NCT06674226: Effects of Ciprofol on Postoperative Delirium and Outcomes in Elderly Patients Undergoing Major Thoracic Surgery
Official title: Effects of Ciprofol on Postoperative Delirium and Outcomes in Elderly Patients Undergoing Major Thoracic Surgery: a Multicentre, Prospective, Single-blind, Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Postoperative Delirium (POD)
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Xiangya Hospital of Central South University
name: The Third Xiangya Hospital of Central South University
name: The First Hospital of Hebei Medical University
name: The First Affiliated Hospital of Nanchang University
name: Tongji Hospital
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
First posted: 2024-11-05
Enrollment: 214
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: There are many factors that make elderly patients prone to POD. On the basis of these factors, surgery and anesthesia can increase the incidence of POD in elderly patients. Deep depth of intraoperative anesthesia and persistent hypotension may increase the risk of POD occurrence in elderly patients. So far, no specific POD prevention method has been found. In recent years, a large number of studies on POD have brought forward more new views on its pathogenesis, prevention and treatment. There is insufficient evidence to recommend specific anesthetic agents and dosages to reduce the risk of POD in elderly patients, and only low-quality evidence to recommend propofol. At present, it is considered that the best way to reduce postoperative delirium is perioperative risk management, to evaluate high-risk patients or patients undergoing high-risk surgery as extensive as possible, and to quantify their risk of postoperative delirium. Effective measures include depth management of anesthesia, multi-modal analgesia management, and optimization of drug intervention.

Ciprofol is a class 1 innovative drug independently developed by China and with global independent intellectual property rights. Ciprofol has been widely used in anesthesiology and critical care medicine. The pre-market phase I-III and post-market data showed that during the induction and maintenance of general anesthesia, Ciprofol had less impact on hemodynamics and more stable anesthesia depth than propofol. Relevant studies have shown that Ciprofol can reduce the risk of hypotension, and can provide better brain oxygenation and more stable intraoperative hemodynamics than propofol. At present, the influence of different sedative drugs on POD incidence in elderly patients remains to be studied. Therefore, we will apply Ciprofol or propofol in elderly patients undergoing thoracic surgery to observe their influence on POD incidence and provide reference for clinical use.

Detailed description: This study was a prospective, single-blinded, randomized controlled study. Elderly patients (≥65 years old) who were to receive elective thoracoscopic lobectomy and pulmonary segmentation under general anesthesia and whose estimated time of anesthesia (from the beginning of anesthesia to the end of surgery) was ≥2 hours were enrolled into this study, and were randomly divided according to 1:1, namely the ciprofol group and the propofol group. Study data of patients were recorded before surgery, during surgery, 7 days after surgery or before discharge.Primary end point: Incidence of postoperative delirium(Incidence of delirium on the first to seventh day after surgery or to the day of discharge (whichever occurs first)).

Eligibility criteria: Inclusion Criteria:

* Age ≥65 years old, gender unlimited;
* Selective thoracoscopic lobectomy and segmental lung resection were performed, and the estimated time of anesthesia (from the beginning of anesthesia to the end of surgery) was ≥2 hours;
* ASA score is Grade I \~III; (Annex 1)
* A BMI of 18.5 to 29.9 kg/m2 \[BMI= weight (Kg)/height (m) 2\] (2013 U.S. Guidelines for the Management of Overweight and Obesity in Adults);
* Postoperative hospital stay more than 72 hours;
* Ethical, patients voluntarily take the test and sign the informed consent.

Exclusion Criteria:

* Emergency surgery; Hypovolemia, shock or coma;
* In addition to general intravenous anesthesia, other anesthesia methods should be combined, such as inhalation anesthesia, epidural anesthesia, peripheral nerve block, etc., but it is not necessary to exclude patients with local infiltration of local anesthetic incision;
* Serious cardiovascular disease, including a history of myocardial infarction within 6 months, bradycardia (resting heart rate \< 50 beats/min); Patients with hypertension whose blood pressure is not satisfactorily controlled (seated systolic blood pressure ≥160 mmHg during screening, and/or diastolic blood pressure ≥100 mmHg during screening); Sitting systolic blood pressure ≤90 mmHg during the screening period; A history of severe heart valve disease.
* Abnormal liver function, AST and/or ALT≥2.5×ULN, TBIL≥1.5×ULN;
* Abnormal renal function, urea or urea nitrogen ≥1.5×ULN, blood creatinine greater than the upper limit of normal;
* Glycated hemoglobin (HbA1c) ≥ 8.5%, fasting blood glucose ≥180 mg/dl (10 mmol/L), blood glucose ≥270mg/dl (15mmol/L) 1 hour after meals, or blood glucose ≥216 mg/dl (12mmol/L) 2 hours after meals;
* Patients with type I and type II expiratory failure
* Preoperative anemia (Hb≤90 g/L), thrombocytopenia (PLT≤80×109/L), hypoproteinemia (Alb≤30 g/L);
* A history of drug use and/or alcohol abuse within the 2 years prior to screening, with alcohol abuse being an average consumption of more than 2 units of alcohol per day (1 unit =360 mL beer or 150 mL of 45 mL liquor or wine with an alcohol concentration of 40%);
* Patients with neurological diseases (stroke, Alzheimer's disease, Parkinson's disease, mental illness, myasthenia grave, etc., within 6 months), psychiatric diseases (schizophrenia, mania, bipolar disorder, insanity, etc.), long-term history of taking psychiatric drugs and cognitive impairment (using the simple mental State Assessment Form (MMSE scale (Annex 2));
* Patients who take sedative sleeping drugs and antiepileptic drugs for a long time;
* Allergic to the investigational drug or contraindicated;
* Participated in other drug clinical trials as a subject within the last 3 months;
* Patients who refused or were unable to cooperate with the study;
* Other conditions that the investigator considers inappropriate to participate in this study.

Primary outcomes:
measure: Incidence of postoperative delirium
timeFrame: up to the seventh day after surgery or on the day of discharge (whichever occurs first).
Secondary outcomes:
measure: Incidence of Emergence delirium
timeFrame: from the onset of extubation to departure of the PACU
measure: The incidence of combined adverse events during induction and maintenance of anesthesia;
timeFrame: During the intervention
measure: Duration of intraoperative hypotension
timeFrame: During the intervention
measure: Minimum mean intraoperative arterial pressure
timeFrame: During the intervention
measure: Duration of WLi < 40
timeFrame: During the intervention
measure: Other adverse events identified during the follow-up period, except POD
timeFrame: up to the seventh day after surgery or on the day of discharge (whichever occurs first).
measure: Length of stay
timeFrame: Perioperatively
measure: First exhaust time
timeFrame: up to the seventh day after surgery or on the day of discharge (whichever occurs first).
measure: Postoperative first time to taking food
timeFrame: up to the seventh day after surgery or on the day of discharge (whichever occurs first).
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital
state: Beijing
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Changsha
country: China
facility: The third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Drum Tower Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Tianlong Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: