NCT07536750

Comparison of the Efficacy and Safety of Ciprofol Versus Propofol for Sedation in ICU Patients Undergoing Non-Invasive Ventilation

Comparison of the Efficacy and Safety of Ciprofol Versus Propofol for Sedation in ICU Patients Undergoing Non-Invasive Ventilation: A Multicenter Retrospective Cohort Study

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 1,680 (estimated)
• Sponsor: Nanfang Hospital, Southern Medical University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Sedation is frequently required in critically ill patients admitted to the intensive care unit (ICU), including those receiving non-invasive respiratory support such as high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or conventional oxygen therapy. Anxiety, agitation, dyspnea, and poor tolerance of respiratory support may compromise treatment adherence and increase the risk of respiratory deterioration and endotracheal intubation. Appropriate sedation may improve patient comfort, facilitate respiratory support, and reduce complications. However, sedation in non-mechanically ventilated ICU patients remains challenging because excessive sedation may lead to respiratory depression or hemodynamic instability. Propofol is commonly used for ICU sedation because of its rapid onset and controllable depth of sedation. Nevertheless, propofol is associated with several adverse effects, including respiratory depression, hypotension, and injection pain, which may limit its use in patients without invasive mechanical ventilation. Ciprofol is a novel short-acting intravenous sedative that acts as a gamma-aminobutyric acid type A (GABA-A) receptor agonist and is structurally related to propofol. Previous studies have demonstrated that ciprofol has rapid onset, predictable sedation, less injection pain, and a potentially lower incidence of respiratory depression and hemodynamic instability compared with propofol. Clinical studies have shown favorable safety and efficacy profiles of ciprofol in procedural sedation, anesthesia induction, and sedation in mechanically ventilated ICU patients. However, evidence regarding its use in ICU patients receiving non-mechanical ventilation is still limited. This study aims to compare the effectiveness and safety of ciprofol versus propofol for sedation in adult ICU patients who are not receiving invasive mechanical ventilation. The study will be conducted as a multicenter retrospective cohort study involving approximately 30 tertiary hospitals in China. Adult ICU patients treated between January 1, 2022 and July 30, 2024 who received intravenous sedation with either ciprofol or propofol while receiving non-invasive respiratory support (including NIV, HFNC, or conventional oxygen therapy) will be included. The primary outcomes are sedation success rate and the incidence of respiratory depression. Sedation success is defined as maintaining the Richmond Agitation-Sedation Scale (RASS) within the target range of -2 to +1 for at least two consecutive hours without discontinuation of the sedation regimen or switching to another sedative. Respiratory depression will be defined based on predefined criteria including severe hypoxemia, markedly reduced respiratory rate, abnormal end-tidal carbon dioxide levels, or apnea. Secondary outcomes include endotracheal intubation rate during the sedation period, ICU length of stay, ICU mortality, and the requirement for vasoactive agents. Propensity score matching and multivariable statistical models will be used to adjust for baseline differences and potential confounders between treatment groups. This real-world study aims to provide evidence regarding the clinical effectiveness and respiratory safety of ciprofol compared with propofol for sedation in ICU patients without invasive mechanical ventilation. The findings may help optimize sedation strategies in critically ill patients receiving non-invasive respiratory support and provide evidence to support future prospective clinical trials.

Detailed description

Background Sedation is commonly required in critically ill patients admitted to the intensive care unit (ICU). In addition to patients receiving invasive mechanical ventilation, many ICU patients who are not intubated may also require sedation during treatment. These patients may receive various forms of non-invasive respiratory support, including high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or conventional oxygen therapy. Anxiety, agitation, dyspnea, and discomfort are common in these patients and may interfere with essential treatments. For example, agitation can reduce tolerance to non-invasive respiratory support, increase oxygen consumption, and potentially worsen respiratory failure. Appropriate sedation can help improve patient comfort, enhance tolerance to respiratory support, and facilitate clinical procedures and monitoring. However, sedation in patients without invasive mechanical ventilation is particularly challenging. Because these patients maintain spontaneous breathing without the protection of an artificial airway, excessive sedation may increase the risk of respiratory depression, hypoxemia, airway obstruction, or the need for emergency endotracheal intubation. Therefore, selecting sedative medications with a favorable balance between effective sedation and respiratory safety is essential in this population. Currently, several sedative agents are used in ICU practice. Benzodiazepines such as midazolam have historically been widely used, but they are associated with delayed awakening, accumulation in patients with organ dysfunction, and an increased risk of delirium. Dexmedetomidine provides lighter sedation and has minimal respiratory depression, but it may cause bradycardia and hypotension and may not always achieve the desired depth of sedation. Propofol is another commonly used sedative in the ICU. It has a rapid onset of action, short duration, and easily adjustable sedation depth, which makes it attractive for clinical use. However, propofol is also associated with several adverse effects, including respiratory depression, hypotension, and injection-site pain. These effects can limit its use in patients who are not mechanically ventilated. Ciprofol is a novel intravenous anesthetic and sedative agent that acts as a gamma-aminobutyric acid type A (GABA-A) receptor agonist. Structurally related to propofol, ciprofol has been developed to improve pharmacologic properties while maintaining similar sedative effects. Previous clinical studies have shown that ciprofol provides rapid onset of sedation and stable sedation depth with potentially fewer adverse effects. In particular, several studies have suggested that ciprofol may be associated with less respiratory depression, lower incidence of hypotension, and less injection pain compared with propofol. Ciprofol has been evaluated in a variety of clinical settings, including procedural sedation for gastrointestinal endoscopy, anesthesia induction for surgery, and sedation in mechanically ventilated ICU patients. These studies generally suggest that ciprofol is effective and safe. However, evidence regarding the use of ciprofol in ICU patients who are not receiving invasive mechanical ventilation remains limited. This population represents an important clinical group because maintaining adequate respiratory drive and avoiding respiratory complications are critical. Therefore, further research is needed to better understand the effectiveness and safety of ciprofol in non-mechanically ventilated ICU patients and to compare its clinical performance with commonly used sedatives such as propofol. Study Rationale Given the pharmacological similarities between ciprofol and propofol and the potential advantages of ciprofol in terms of respiratory and hemodynamic safety, comparing these two drugs in real-world ICU practice is clinically relevant. Understanding whether ciprofol provides comparable sedation efficacy while reducing adverse events could help clinicians select safer sedation strategies for patients receiving non-invasive respiratory support. In many ICUs, clinicians must balance the need for adequate sedation with the need to preserve spontaneous breathing and stable hemodynamics. Real-world clinical data can provide valuable insights into how sedative medications perform in routine practice across diverse patient populations. This study is designed as a multicenter retrospective cohort study using data from routine clinical care. By including patients from multiple tertiary hospitals, the study aims to capture real-world sedation practices and outcomes in critically ill patients receiving non-invasive respiratory support. Study Objectives The primary objective of this study is to evaluate and compare the effectiveness and safety of ciprofol and propofol for sedation in adult ICU patients who are not receiving invasive mechanical ventilation. The study specifically aims to assess whether ciprofol provides comparable sedation effectiveness while maintaining an acceptable safety profile, particularly in terms of respiratory function. Secondary objectives include evaluating the association between the choice of sedative agent and broader clinical outcomes, such as the need for endotracheal intubation, length of ICU stay, use of vasoactive medications, and ICU mortality. In addition, subgroup analyses based on the type of respiratory support may help identify patient populations that could benefit most from specific sedation strategies. Study Design This study is a multicenter retrospective observational cohort study. Data will be collected from approximately 30 tertiary hospitals in China. The study will include adult ICU patients treated between January 1, 2022 and July 30, 2024. Eligible patients are those who received intravenous sedation with either ciprofol or propofol during their ICU stay while not receiving invasive mechanical ventilation. Patients may have been receiving non-invasive respiratory support such as high-flow nasal cannula, non-invasive ventilation, or conventional oxygen therapy at the time sedation was initiated. The study is observational and does not involve any intervention beyond routine clinical practice. Treatment decisions, including the choice of sedative medication and dosing adjustments, were made by the treating physicians according to standard clinical care. No additional procedures, tests, or visits are required for the purposes of this study. Because the study uses existing medical records and does not alter patient management, the study poses minimal risk to participants. Informed consent may be waived according to local ethical regulations where applicable. Data Collection Clinical data will be obtained from electronic medical records and other routinely collected clinical documentation. Data collected will include demographic characteristics, medical history, clinical diagnoses, and severity of illness scores such as APACHE II and SOFA scores. Information related to sedation therapy will also be recorded. This includes the type of sedative agent used (ciprofol or propofol), dosing information, duration of drug exposure, and any adjustments made during treatment. Sedation depth will be assessed using the Richmond Agitation-Sedation Scale (RASS), which is commonly used in ICU practice to evaluate the level of sedation. Vital signs and respiratory parameters recorded during sedation will also be collected, including respiratory rate, oxygen saturation, blood pressure, and heart rate. Information about the type and settings of respiratory support will be documented, including parameters for non-invasive ventilation and high-flow nasal oxygen therapy. The use of vasoactive medications and other relevant treatments during the observation period will also be recorded. Clinical outcomes such as the occurrence of endotracheal intubation, ICU length of stay, and mortality during ICU hospitalization will be collected. All data will be de-identified prior to analysis to protect patient privacy. Outcome Measures The primary outcomes of the study are sedation success and the occurrence of respiratory depression. Sedation success is defined as maintaining the Richmond Agitation-Sedation Scale (RASS) score within the target range of -2 to +1 for at least two consecutive hours without premature discontinuation of the sedation regimen or switching to another sedative medication. Respiratory depression will be identified based on predefined criteria, including severe reductions in respiratory rate, significant decreases in oxygen saturation, abnormal end-tidal carbon dioxide levels, or episodes of apnea. Secondary outcomes include the rate of endotracheal intubation during the sedation period, length of ICU stay, ICU mortality, and the requirement for vasoactive medications. These outcomes reflect important aspects of patient recovery, clinical stability, and overall ICU resource utilization. Statistical Analysis Statistical analyses will be conducted using standard statistical software. Baseline characteristics of patients receiving ciprofol and propofol will be summarized using appropriate descriptive statistics. To reduce potential bias due to differences in patient characteristics between treatment groups, propensity score matching will be used. This method allows patients in the two groups to be matched based on relevant clinical variables, creating more comparable cohorts for analysis. After matching, outcomes will be compared between the ciprofol and propofol groups using appropriate statistical tests. Multivariable regression models may also be used to evaluate associations between sedative choice and clinical outcomes while adjusting for potential confounding factors. All statistical tests will be two-sided, and results will be considered statistically significant if the p-value is less than 0.05. Ethical Considerations This study will be conducted in accordance with ethical principles for medical research involving human subjects and applicable regulatory requirements. The study protocol will be reviewed and approved by the appropriate institutional ethics committees before study initiation. Because the study uses retrospective data collected during routine clinical care and does not involve additional interventions, the requirement for informed consent may be waived in accordance with local regulations. All patient data will be anonymized to protect privacy and confidentiality. Data will be stored securely and used only for research purposes. Expected Impact By comparing ciprofol and propofol in a large real-world ICU population, this study aims to provide clinically meaningful evidence regarding sedation management in patients receiving non-invasive respiratory support. The results may help clinicians better understand the relative benefits and risks of these sedative agents and may contribute to optimizing sedation strategies in critically ill patients. In addition, the findings may support the design of future prospective studies or randomized clinical trials investigating sedation practices in the ICU. Ultimately, improving sedation strategies may enhance patient comfort, reduce complications, and improve clinical outcomes for critically ill patients.

Conditions

• Respiratory Failure
• Critical Illness

Timeline

• Start date: 2025-11-24
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2026-04-17
• Last updated: 2026-04-17

Locations

1 site across 1 country: China