Sedation in ICU Patients With Mechanical Ventilation

Efficacy and Safety of Ciprofol Versus Propofol for Sedation in ICU Patients With Mechanical Ventilation: A Multi-Center, Double-Blind, Randomized Controlled Trial

Background: Sedation is a cornerstone of management for mechanically ventilated patients in the intensive care unit (ICU). Achieving early target sedation while maintaining hemodynamic stability remains a major clinical challenge. Ciprofol, a novel intravenous sedative agent structurally derived from propofol, has shown promising efficacy and a potentially improved hemodynamic profile in preclinical and phase II/III studies. However, high-quality evidence from large, multicenter randomized trials in real-world ICU settings is lacking.

Objective: To evaluate the efficacy and safety of ciprofol versus propofol for sedation in mechanically ventilated ICU patients, as assessed by the incidence of early successful sedation without hypotension.

Methods: This is a multicenter, randomized, double-blind, parallel-group, active-controlled, noninferiority clinical trial conducted across 31 centers in China. A total of 366 patients will be randomized in a 1:1 ratio to receive either ciprofol or propofol. Eligible patients are adults (aged 18-80 years) admitted to the ICU receiving mechanical ventilation, with an expected sedation duration of 6-24 hours and a target Richmond Agitation-Sedation Scale (RASS) of +1 to -2. Key exclusion criteria include known allergy to ciprofol, BMI <18 or >30 kg/m², prior sedation for >3 days, severe cardiovascular, hepatic or renal dysfunction, Glasgow Coma Scale ≤12, expected survival ≤24 hours, pregnancy or lactation, and participation in other drug trials.

Patients will receive a loading dose (ciprofol 0.1 mg/kg or propofol 0.5 mg/kg) over 4 minutes, followed by a maintenance infusion titrated to achieve the target RASS. Remifentanil will be used for analgesia throughout. The primary composite outcome is successful sedation without hypotension within 30 minutes of study drug administration, defined as: (1) RASS within the target range of +1 to -2; (2) no use of rescue sedation; and (3) no occurrence of hypotension. Hypotension is defined as systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg, mean arterial pressure <70 mmHg, or a >30% drop from baseline. Secondary outcomes include sedation success without hypotension at 1 hour, sedation without circulatory depression (hypotension or bradycardia) at 1 hour, drug utilization, duration of mechanical ventilation, extubation time, awakening time, delirium incidence (CAM-ICU), ICU length of stay, 28-day mortality, and safety profiles.

Based on an assumed 92% incidence in the ciprofol group versus 82% in the propofol group, with a two-sided alpha of 0.05 and 80% power, and allowing for a 5% dropout rate, the required sample size is 183 patients per group, totaling 366 patients. Analysis will be performed on the intention-to-treat population using logistic regression for the primary outcome, with results expressed as risk difference and relative risk with 95% confidence intervals.

Ethics and Dissemination: The study protocol has been approved by the ethics committee of the coordinating center and will be submitted to all participating sites. The trial is registered with ClinicalTrials.gov (NCT06538883). Results will be disseminated through peer-reviewed publications and academic presentations.

Keywords: Ciprofol, Propofol, Intensive care unit, Mechanical ventilation, Sedation, Hypotension, Randomized controlled trial

Study Overview

• Status: Completed
• Conditions: Sedation; Mechanical Ventilation
• Intervention / Treatment: Drug: Sedation with Propofol; Drug: Ciprofol

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital, Southeast University, No. 87, Dingjiaqiao Road, Gulou District, Nanjing, 210009, People's Republic of China.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria (patients who met all the following criteria):

1. Adults are sequentially admitted to ICU undergoing mechanical ventilation; Patients are expected to need 6-24 hours of sedation for the target RASS ranged from +1 to -2 after randomization;
2. Aged ≥ 18 and ≤ 80 years old, with no gender requirement;
3. The patients or their family members fully understood the objectives and significance of this study and voluntarily participated and signed informed consent forms.

Exclusion criteria (patients who met 1 of the following criteria were excluded):

1. Patients known to be allergic or contraindicated to ciprofol. 2. BMI<18 kg/m2 or >30 kg/m2. 3. Patients who had received sedation for more than 3 days in an ICU or in a general ward prior to being transferred to the ICU before signing an informed consent form.

4. Patients have the following medical history or evidence of any of the following conditions at screening, which may increase the sedation/anesthesia risk:

1. Cardiovascular system: New York Heart Association (NYHA) Class III and IV heart failure, Adams-stokes syndrome; patients who required vasopressor (equivalent norepinephrine ≥ 1μg/kg/min) to maintain a normal blood pressure.
2. Patients with hepatic and renal failure (liver function: refer to Child-Pugh grade C; renal function: eGFR ≤ 30 mL/(min·1.73 m2) [eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation: eGFR = 175 × serum creatinine (SCr) - 1.234 × age - 0.179 × 0.79 (females)]; patients undergoing dialysis.
3. Patients with grand mal epilepsy and convulsion; a Glasgow coma scale (GCS) ≤ 12 points.

5. Patients with an expected survival of ≤ 24 h. 6. Pregnant or lactating females. 7. Patients participated in other drug clinical trials before screening. 8. Other conditions that patients were judged by the investigator to be unsuitable for inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol	Drug: Sedation with Propofol; During the drug administration period, propofol were IV infused at loading doses of 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Propofol were then immediately administered at an initial maintenance dose of 1.5 mg/kg/hr, with a target sedation depth of RASS +1 to -2, based on the Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) guideline.
Experimental: Ciprofol	Drug: Ciprofol; During the drug administration period, ciprofol were IV infused at loading doses of 0.1 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr, with a target sedation depth of RASS +1 to -2, based on the Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) guideline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is the rate of successful sedation without hypotension	The primary outcome is the rate of successful sedation without hypotension, which have to meet the following three criteria simultaneously: 1) Sedation within the RASS target (+1 to -2); 2) No rescue therapy is used; 3) No hypotension occurs, within the first 30 minutes of administering the study drug.	within the first 30 minutes of administering the study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of within sedation target (RASS: +1 to -2) without hypotension in the first 1hour of administering the study drug;		within the first 1hour of administering the study drug
the rate of within sedation target (RASS: +1 to -2) without circulatory inhibition (defined as either hypotension or bradycardia) in the first 1hour of administering the study drug;		within the first 1hour of administering the study drug
Usage of study drugs	the total additional dose will be recorded;	within the first 24hours of administering the study drug
Incidence of delirium	Incidence of delirium, which is assessed using the CAM-ICU;	from administation of study drug until the time of awakening from sedation (RASS ≥ 0) or death from any cause, whichever came first, assessed up to 28 days
Duration of mechanical ventilation	Duration of mechanical ventilation: defined as the time from randomization to extubation in 28 days	from randomization until the date of first extubation or date of death from any cause, whichever came first, assessed up to 28 days
Extubation time	defined as time from stopping the study drug to extubation, or death from any cause; not applicable for patients who withdraw early or do not plan to extubate after stopping the drug, in 28 days;	from stopping the study drug to extubation, or death from any cause, or 28 days
Awakening time	defined as the time from stopping the study drug to awakening from sedation (RASS ≥ 0) in 24h after stopping the drug. If RASS is ≥ 0 at the time of stopping the drug, the awakening time is recorded as 0; If RASS is less than 0 in 24h after stopping the drug, the awakening time is recorded as 24h;	from stopping the study drug until the time of awakening from sedation (RASS ≥ 0) or death from any cause, whichever came first, assessed up to 24h after stopping the drug.
Length of ICU stay	defined as the time from randomization to discharge from the ICU;	the time from randomization to discharge from the ICU or death from any cause, whichever came first, assessed up to 28 days
The 28-day mortality	all caused mortality within 28 days.	from randomization to 28 days
Incidence of hypotension	Hypotension was defined as SBP < 90 mmHg, or DBP < 60 mmHg, or MAP < 70 mmHg, or a drop of more than 30% from baseline, or as determined by the investigator; and the use of vasopressor medications will be recorded;	from randomization to 48 hours after the end of study drug administration
Incidence of bradycardia	HR < 40 bpm or a drop of more than 30% from baseline; the use of medications for bradycardia intervention	from randomization to 48 hours after the end of study drug administration

Collaborators and Investigators

• Sponsor: Zhongda Hospital
• Collaborators: First People's Hospital of Hangzhou; The First Affiliated Hospital of Nanchang University; First Affiliated Hospital, Sun Yat-Sen University; First Affiliated Hospital Xi'an Jiaotong University; Zhongnan Hospital; Henan Provincial People's Hospital; Xuzhou Central Hospital; Hebei Medical University Fourth Hospital; Renmin Hospital of Wuhan University; Sichuan Academy of Medical Sciences; Fifth Affiliated Hospital of Xinjiang Medical University; China-Japan Union Hospital, Jilin University; The First People's Hospital of Lianyungang; Second Affiliated Hospital of Suzhou University; Jiangxi Provincial People's Hopital; First Affiliated Hospital of Suzhou Medical College; Taian City Central Hospital; Huai'an First People's Hospital; The First People's Hospital of Zunyi; First Affiliated Hospital of Kunming Medical University; Suqian First Hospital; The First Affiliated Hospital of Air Force Medicial University; The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial); Zhongnan University Xiangya Second Hospital; Anhui provincial chest hospital; The Guangxi Zhuang Autonomous Region People's Hospital; The Ninth People's Hospital of Suzhou; Xuzhou Medical University Hospital; Jinan City People's Hospital; Jiangsu Subei People's Hospital; The first People's Hospital of Yancheng City

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Actual): April 30, 2026
• Study Completion (Actual): April 30, 2026

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ICU; Sedation; Propofol; Mechanical Ventilation; Ciprofol
• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Propofol; (2-(1R)-1-cyclopropyl)ethyl-6-isopropyl-phenol
• Other Study ID Numbers: SAME study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No