Remimazolam vs Propofol for Long-Term Sedation in Mechanically Ventilated ICU Patients

This multicenter, randomized, controlled, non-inferiority trial is designed to determine whether remimazolam is non-inferior to propofol for prolonged sedation in adult ICU patients requiring mechanical ventilation for ≥48 hours. A total of 274 patients will be enrolled across 21 geographically diverse hospitals in China and allocated in a 1:1 ratio to receive either remimazolam or propofol using centralized, computer-generated block randomization. The primary endpoint is time to successful extubation-defined as extubation without reintubation within 48 hours. Secondary endpoints include quantitative measures of sedation quality (e.g., RASS, time to target sedation), clinically outcomes (e.g., length of ICU stay, 28-day and 90-day all-cause mortality), and comprehensive safety evaluation (e.g., incidence and severity of hypotension, post-sedation delirium).

Inclusion Criteria: 1. Age ≥ 18 years; 2. The interval from ICU admission to the first receipt of mechanical ventilation is no more than 48 h, and the expected total duration of mechanical ventilation is ≥ 48 h; 3. At the time of randomization, more than 24 h of further mechanical ventilation is anticipated; 4. The attending clinician determines that sedation therapy is required; 5. the subject and/or their legal guardian signs the informed consent form (ICF); 6. Women and men of childbearing potential must agree to use highly effective contraception together with their partner and to refrain from donating oocytes or sperm from the time of ICF signing until 28 days after the last dose of study drug. Exclusion Criteria: 1. History of hypersensitivity to benzodiazepines, propofol, remifentanil, or to any of their components or excipients; 2. Severe neurological disease (e.g., myasthenia gravis, severe depression, schizophrenia, severe traumatic brain injury, massive cerebral infarction, status epilepticus, intracranial tumor, post-neurosurgical status); 3. Post-cardiac arrest (with clinician-assessed hypoxic-ischemic brain injury); 4. Subjects who require or are expected to require neuromuscular blocking agents after ICU admission; 5. Pregnant or breastfeeding women; 6. Life expectancy less than 24 hours; 7. Receipt of palliative care; 8. Hospice patients; 9. Severe hepatic impairment (Child-Pugh class C); 10. Participation in another clinical trial of an investigational drug with prior receipt of that drug; 11. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this clinical trial.