Effects of Ciprofol on Myocardial Injury After Non-cardiac Surgery in Video-Assisted Thoracoscopic Surgery

Phase 4

Not yet recruiting

• Conditions: Myocardial Injury; Thoracic Diseases; Thoracoscopic Surgery
• Interventions: Drug: ciprofol; Drug: Propofol

• Registration Number: NCT07028593
• Lead Sponsor: Tongji Hospital

Brief Summary

Myocardial injury after noncardiac surgery (MINS) refers to postoperative elevation of cardiac troponin (cTn) levels caused by underlying ischemic mechanisms (i.e., coronary artery supply-demand imbalance or atherosclerotic thrombosis) without obvious non-ischemic causes (such as pulmonary embolism), with at least one cTn concentration exceeding the 99th percentile of the test reference upper limit, regardless of whether clinical symptoms and ECG changes are present. MINS, including myocardial infarction and ischemic myocardial injury, typically occurs within 30 days after surgery, most commonly within the first 2 postoperative days. It is an independent risk factor for 30-day postoperative mortality and is also closely associated with increased risk of mortality and vascular complications within 2 years . MINS is a common cardiovascular complication after thoracic surgery. Therefore, reducing the incidence of MINS in non-cardiac thoracic surgery to improve patient outcomes is a critical issue in anesthetic management for thoracic surgery.

Ciprofol is a Class 1 innovative drug independently developed in China with global intellectual property rights. Currently, Ciprofol has completed Phase III clinical trials in China and the United States; its approved indications in China include sedation or anesthesia for various diagnostic procedures, general anesthesia for surgical operations, and sedation during intensive care unit (ICU) stays. Completed drug clinical trials and published clinical trial data of Ciprofol indicate that it can better maintain circulatory stability and ideal anesthetic depth during anesthesia induction and maintenance, making it a promising intravenous general anesthetic alternative to propofol.

Maintaining hemodynamic stability is an important measure to reduce cardiovascular complications during the perioperative period. Given the good circulatory stability and sedative efficacy of Ciprofol, this study aims to investigate the impact of Ciprofol on MINS in non-cardiac thoracic surgery.

Detailed Description

Lung cancer ranks first in both incidence and mortality among malignant tumors in China. In 2022, there were 1,060,600 new lung cancer cases, accounting for 22.0% of all malignant tumors, and 733,300 deaths, accounting for 28.5% of all malignant tumor deaths. Radical surgical resection is the recommended preferred treatment for stage I and II non-small cell lung cancer. Video-assisted thoracoscopic surgery (VATS) for anatomic lung resection has better safety and long-term efficacy than traditional surgical methods, with more than 73.7% of lung cancer surgeries in China using thoracoscopic approaches. Thoracic surgery easily induces significant perioperative hemodynamic fluctuations, increasing the risk of perioperative cardiovascular and cerebrovascular complications, thus posing great challenges to perioperative anesthetic safety and long-term patient outcomes.

Myocardial injury after noncardiac surgery (MINS) refers to postoperative elevation of cardiac troponin (cTn) levels caused by underlying ischemic mechanisms (i.e., coronary artery supply-demand imbalance or atherosclerotic thrombosis) without obvious non-ischemic causes (such as pulmonary embolism), with at least one cTn concentration exceeding the 99th percentile of the test reference upper limit, regardless of whether clinical symptoms and ECG changes are present. MINS, including myocardial infarction and ischemic myocardial injury, typically occurs within 30 days after surgery, most commonly within the first 2 postoperative days. It is an independent risk factor for 30-day postoperative mortality and is also closely associated with increased risk of mortality and vascular complications within 2 years. MINS is a common cardiovascular complication after thoracic surgery; the COP-AF study found that the incidence of MINS in non-cardiac thoracic surgery is 20.3% . Therefore, reducing the incidence of MINS in non-cardiac thoracic surgery to improve patient outcomes is a critical issue in anesthetic management for thoracic surgery.

Severe hemodynamic fluctuations are one of the important causes of perioperative induction of MINS, thus maintaining hemodynamic stability is a critical step to reduce MINS. Propofol is the most commonly used drug for anesthesia induction and maintenance in clinical practice, with advantages such as rapid onset, strong sedative efficacy, and quick recovery. However, due to its significant circulatory inhibitory effects, the incidence of intraoperative hypotension induced and maintained by propofol in patients without cardiovascular diseases is 25%-40%, increasing the risk of perioperative hypotension and adverse cardiovascular events, which poses great challenges to anesthetic management. Additionally, 80% of patients receiving propofol experience injection pain of varying degrees, which also reduces patient comfort during treatment. Therefore, developing a sedative with both good sedative efficacy and no or low circulatory inhibition has long been a desirable goal for anesthesiologists.

Ciprofol is a Class 1 innovative drug independently developed in China with global intellectual property rights. Its molecular structure is an analog of propofol (2,6-diisopropylphenol). Both Ciprofol and propofol act on γ-aminobutyric acid type A (GABA-A) receptors, causing hyperpolarization of GABAergic neurons, reducing the success rate of action potential generation, and achieving inhibition of the central nervous system to produce short and rapid sedative or anesthetic effects. Pharmacologically, Ciprofol not only retains the characteristics of propofol such as rapid onset, rapid elimination, and high sedative efficacy but also has a higher drug cost-effectiveness ratio and therapeutic index (in mouse experiments, the median effective dose for sedation of Ciprofol is 1.5 mg/kg, the median lethal dose is 9.9 mg/kg, and the therapeutic index is 6.6, while that of propofol is only 2.8). Furthermore, due to the lower drug concentration in the aqueous phase of the Ciprofol emulsion, the risk of injection pain is much lower than that of propofol, improving treatment comfort. Currently, Ciprofol has completed Phase III clinical trials in China and the United States; its approved indications in China include sedation or anesthesia for various diagnostic procedures, general anesthesia for surgical operations, and sedation during intensive care unit (ICU) stays. Completed drug clinical trials and published post-marketing clinical trial data of Ciprofol indicate that it can better maintain circulatory stability and ideal anesthetic depth during anesthesia induction and maintenance, making it a promising intravenous general anesthetic alternative to propofol.

Maintaining hemodynamic stability is an important measure to reduce cardiovascular complications during the perioperative period. Given the good circulatory stability and sedative efficacy of Ciprofol, this study aims to investigate the impact of Ciprofol on MINS in non-cardiac thoracic surgery.

After data collection, full Analysis Set (FAS): A population derived by minimally and reasonably excluding certain cases under the principle of Intention-to-Treat (ITT), where cases included in the FAS should not seriously violate the inclusion criteria. FAS will be used for the analysis of baseline data and primary efficacy endpoints.

Per-Protocol Set (PPS): All cases that comply with the trial protocol, are well-tolerated (patients who completed PED procedures), and have completed the content specified in the case report form. PPS is used for the analysis of primary efficacy endpoints.

Safety Set (SS): Refers to the actual data of subjects who received at least one dose of treatment after randomization and have recorded safety indicators.

Study Timeline

• Study First Submitted: 2025-05-29
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-11
• Last Update Submitted: 2025-06-11
• Study First Posted: 2025-06-19
• Last Update Posted: 2025-06-19
• Study Start: 2025-07
• Primary Completion: 2026-10
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1058

Inclusion Criteria

1. Scheduled for elective video-assisted thoracoscopic (VATS)-assisted thoracic surgery (lobectomy, segmentectomy, wedge resection of two or more lung tissues, mediastinal tumor resection) under general anesthesia;
2. Aged 45 to 80 years (inclusive) at the time of randomization;
3. Expected postoperative hospital stay of ≥3 days;
4. Signed a written informed consent to participate in the study.

Exclusion Criteria

1. Patients allergic to propofol, Ciprofol, or analogs of drug excipient components (soybeans, eggs, milk);
2. Patients with unstable angina;
3. Patients with congestive heart failure or hemodynamic instability requiring vasopressor agents;
4. Patients with severe COPD (FEV1 < 1 L);
5. Glomerular filtration rate [eGFR] < 30 mL/min/1.73m²;
6. Patients with severe hepatic dysfunction (ALT or AST elevation exceeding 1.5 times the upper limit of normal);
7. Male or female patients planning to conceive within the next 3 months;
8. Pregnant or lactating female patients;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ciprofol group	ciprofol	Slowly administer sufentanil 0.2 μg/kg to 0.7 μg/kg via intravenous injection; cis-atracurium 0.15 mg/kg to 0.20 mg/kg; Ciprofol 0.4 ml/kg to 0.6 ml/kg via slow intravenous injection. The injection time for all drugs is 2 minutes.
propofol group	Propofol	Slowly administer sufentanil 0.2 μg/kg to 0.7 μg/kg via intravenous injection; cis-atracurium 0.15 mg/kg to 0.20 mg/kg; propofol injection 0.1 ml/kg to 0.25 ml/kg slowly via intravenous injection. The injection time for all drugs is 2 minutes.

Primary Outcome Measures

Name	Time	Method
the incidence of myocardial Injury after non-cardiac surgery	Within the first 30 days after surgery	Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs

Secondary Outcome Measures

Name	Time	Method
The incidence and duration of perioperative hypotension	between anesthesia induction and postoperative first 24 hour	assessing the effect of interventions on cardiovascular stability
30-day postoperative mortality rate	Within the first 30 days after surgery	assessing the survival outcome
New-onset myocardial infarction	Within the first 30 days after surgery	assessing the cardiovascular complications
The proportion of new-onset atrial fibrillation	perioperatively	diagnosed by 12 lead ECG.
The proportion of new-onset non-atrial fibrillation arrhythmia	perioperatively	diagnosed by 12 lead ECG.

Trial Locations

Locations (1)

Tongji hospital; 🇨🇳 Wuhan, China