A Study Evaluating the Efficacy and Safety of HSK3486 for Sedation

A Multi-center, Open-label, Randomized, Propofol-controlled Study Evaluating the Efficacy and Safety of Intravenous Administration of HSK3486 Injectable Emulsion for Sedation in Intensive Care (ICU) Patients Undergoing Mechanical Ventilation

This is a multi-center, open-label, randomized, propofol-controlled phase II clinical trial.A total of ICU patients undergoing mechanical ventilation are intended to be enrolled and randomly assigned to HSK3486 group and propofol group in a 2:1 ratio.

Inclusion Criteria:

1. Patients who need tracheal intubation for mechanical ventilation and need 6-24 h of sedation after randomization, as anticipated;
2. The target RASS score is between +1 and -2;
3. 18 ≤ age < 80 years old; with no restriction on gender;
4. 18 kg/m2 ≤ BMI ≤ 30 kg/m2;
5. The patients or their family members well understand the purpose and significance of the trial, voluntarily participate in this clinical trial, and sign the informed consent form.

Exclusion Criteria:

1. Patients known to be allergic to eggs, soy products, opioids and their antidotes, and propofol; patients having contraindications to propofol, opioids and their antidotes;

2. Patients having the following medical history or evidence at screening, which may increase sedation/anesthesia risk:

   1. Cardiovascular system: Class III and IV heart failure by New York Heart Association (NYHA), Adams-Stokes syndrome; acute coronary syndrome (ACS) within 6 months prior to screening; bradycardia requiring medications and/or heart rate ≤ 50 beats/min; serious arrhythmia history such as Degree II-III atrioventricular block (excluding patients with pacemakers); acute and chronic myocarditis; systolic pressure ≤ 90 mmHg even when large dose of vasoactive drug (such as norepinephrine ≥ 0.6 μg/kg/min) is used;
   2. Patients with mental disorders (such as schizophrenia, depression, etc.) and cognitive impairment; past abuse history of psychotropics and anesthetics, and long-term use of psychotropics;
   3. Patients with moderate to severe hepatic and renal dysfunctions (liver function: Child-Pugh Grade B and C, scale in Annex 9; renal function: glomerular filtration rate eGFR ≤ 60 mL/(min•1.73 m2) [eGFR is calculated with the Modification of Diet in Renal Disease (MDRD) formula: eGFR = 186 × serum creatinine (SCr)-1.154 × age-0.203 × 0.742 (female)]; patients under dialysis;
   4. Epileptic seizures, convulsions; craniocerebral injury, intracranial hypertension, cerebral aneurysms; Glasgow Coma Score (GCS) ≤ 12 (scale in Annex 6); SOFA > 9 (scale in Annex 7);
   5. Expected survival ≤ 72 h;

3. Laboratory measures at screening period meet the following criteria:

   1. Neutrophil count ≤ 1.0 × 10^9/L;
   2. Platelet count ≤ 50 × 10^9/L;
   3. Hemoglobin ≤ 70 g/L;

4. Pregnant or lactating females; fertile females or males reluctant to receive contraception through the study; any subject planning for pregnancy within 1 month after the study (including male subject);

5. Participated in other drug clinical trials within 1 month prior to screening; Other reasons rendering a subject unsuitable for participation in this study as per the judgment of the investigator.