Efficacy and Safety of Ciprofol Versus Propofol for Sedation in ICU Patients With Mechanical Ventilation: A Multi-Center, Double-Blind, Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 366
- 试验地点
- 1
- 主要终点
- The primary outcome is the rate of successful sedation without hypotension
研究概览
简要总结
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
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(patients who met all the following criteria):
- •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;
- •Aged ≥ 18 and ≤ 80 years old, with no gender requirement;
- •The patients or their family members fully understood the objectives and significance of this study and voluntarily participated and signed informed consent forms.
排除标准
- •(patients who met 1 of the following criteria were excluded):
- •1. Patients known to be allergic or contraindicated to ciprofol.
- •BMI<18 kg/m2 or >30 kg/m
- •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:
- •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.
- •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.
- •Patients with grand mal epilepsy and convulsion; a Glasgow coma scale (GCS) ≤ 12 points.
- •5. Patients with an expected survival of ≤ 24 h.
- •Pregnant or lactating females.
- •Patients participated in other drug clinical trials before screening.
- •Other conditions that patients were judged by the investigator to be unsuitable for inclusion in the study.
研究组 & 干预措施
Ciprofol
干预措施: Ciprofol (Drug)
Propofol
干预措施: Sedation with Propofol (Drug)
结局指标
主要结局
The primary outcome is the rate of successful sedation without hypotension
时间窗: within the first 30 minutes of administering the study drug
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.
次要结局
- The 28-day mortality(from administation of study drug to 28 days)
- Incidence of hypotension(from the time of signing informed consent to 2 hours after the end of study drug administration)
- Incidence of bradycardia(from the time of signing informed consent to 2 hours after the end of study drug administration)
- Usage of study drugs(within the first 24hours of administering the study drug)
- 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)
- Extubation time(from intubation (for patients intubated after ICU admission) or ICU admission (for patients admitted with intubation) to extubation)
- 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)
- Duration of mechanical ventilation(from intubation (for patients intubated after ICU admission) or ICU admission (for patients admitted with intubation) until the date of first estubation or date of death from any cause, whichever came first, assessed up to 28 days)
- Awakening time(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 28 days)
- Incidence of delirium(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)
- Length of ICU stay(the time from ICU admission to discharge from the ICU or death from any cause, whichever came first, assessed up to 28 days)
- Duration of mechanical ventilation(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(from stopping the study drug to extubation, or death from any cause, or 28 days)
- Awakening time(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(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(from randomization to 28 days)
- Incidence of hypotension(from randomization to 48 hours after the end of study drug administration)
- Incidence of bradycardia(from randomization to 48 hours after the end of study drug administration)
研究者
Fei Peng
Principal Investigator
Zhongda Hospital