Sedation in ICU Patients With Mechanical Ventilation

NCT06538883 | Completed Phase 4

• 1 other identifier: SAME study
• Study Type: interventional
• Target: 366
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Sedation; Mechanical Ventilation; ICU; Ciprofol; Propofol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

  within the first 24hours of administering the study drug

• 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

Study Arms (2)

Ciprofol

EXPERIMENTAL

Drug: Ciprofol

Propofol

ACTIVE COMPARATOR

Drug: Sedation with Propofol

Interventions

Sedation with Propofol DRUG

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.

Propofol

Ciprofol DRUG

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.

Ciprofol

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \. 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.
• \. 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.

Sponsors & Collaborators

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

Study Sites (1)

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

Nanjing, Jiangsu, 210009, China

Location

MeSH Terms

Interventions

(2-(1R)-1-cyclopropyl)ethyl-6-isopropyl-phenol; Propofol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: August 6, 2024
• Study Start: August 1, 2024
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)