Sedation in ICU Patients With Mechanical Ventilation

Summary

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

Conditions

• Sedation
• Mechanical Ventilation

Interventions

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.

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.

Sponsors & Collaborators

• The First Affiliated Hospital of Air Force Medicial University

  collaborator OTHER

• First Affiliated Hospital, Sun Yat-Sen University

  collaborator OTHER

• Zhongnan University Xiangya Second Hospital

  collaborator UNKNOWN

• Renmin Hospital of Wuhan University

  collaborator OTHER

• First Affiliated Hospital of Suzhou Medical College

  collaborator OTHER

• The First Affiliated Hospital of Nanchang University

  collaborator OTHER

• China-Japan Union Hospital, Jilin University

  collaborator OTHER

• Zhongnan Hospital

  collaborator OTHER

• The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial)

  collaborator OTHER

• First Affiliated Hospital Xi'an Jiaotong University

  collaborator OTHER

• First Affiliated Hospital of Kunming Medical University

  collaborator OTHER

• Sichuan Academy of Medical Sciences

  collaborator OTHER

• Anhui provincial chest hospital

  collaborator UNKNOWN

• The Guangxi Zhuang Autonomous Region People's Hospital

  collaborator UNKNOWN

• Second Affiliated Hospital of Suzhou University

  collaborator OTHER

• The Ninth People's Hospital of Suzhou

  collaborator UNKNOWN

• Fifth Affiliated Hospital of Xinjiang Medical University

  collaborator OTHER

• Xuzhou Medical University Hospital

  collaborator UNKNOWN

• First People's Hospital of Hangzhou

  collaborator OTHER

• Hebei Medical University Fourth Hospital

  collaborator OTHER

• Huai'an First People's Hospital

  collaborator OTHER

• Jinan City People's Hospital

  collaborator UNKNOWN

• The First People's Hospital of Lianyungang

  collaborator OTHER

• Jiangsu Subei People's Hospital

  collaborator UNKNOWN

• Suqian First Hospital

  collaborator OTHER

• Taian City Central Hospital

  collaborator OTHER

• Xuzhou Central Hospital

  collaborator OTHER

• The first People's Hospital of Yancheng City

  collaborator UNKNOWN

• The First People's Hospital of Zunyi

  collaborator OTHER

• Jiangxi Provincial People's Hopital

  collaborator OTHER

• Henan Provincial People's Hospital

  collaborator OTHER

• Zhongda Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-08-01

Primary Completion

2026-04-30

Completion

2026-04-30

Countries

• China

Study Locations