A Clinical Study Evaluating Sedation of Intravenous Administration of HSK3486 in ICU Patients Undergoing Long-Term Mechanical Ventilation

A Multi-Center, Randomized, Open-Label, Propofol-Controlled Exploratory Clinical Study Evaluating Sedation of Intravenous Administration of HSK3486 Injectable Emulsion in ICU Patients Undergoing Long-Term Mechanical Ventilation

This is a multi-center, randomized, open-label, propofol-controlled exploratory clinical study. In this study, 20 ICU patients undergoing mechanical ventilation are expected to be enrolled and will be randomly assigned to the HSK3486 group and the propofol group in a 1:1 ratio. This study is not blinded as it is open-label.

Study Overview

• Status: Completed
• Conditions: Sedation in Intensive Care
• Intervention / Treatment: Drug: HSK3486; Drug: Propofol

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Xinjiang, China
    • The First Affiliated Hospital of Xinjiang Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who require tracheal intubation for mechanical ventilation, with expected sedation duration of longer than 96 h;
2. Patients requiring a target RASS score of -1 to -2 for sedation;
3. Aged ≥ 18 and < 80 years old, with no gender requirement;
4. BMI ≥ 18 kg/m2 and ≤ 30 kg/m2;
5. The patients or their family members fully understand the objectives and significance of this study, and voluntarily participate in this clinical study and sign the informed consent form.

Exclusion Criteria:

1. Patients known to be allergic to eggs, soy products, opioids and their antidotes, and Propofol; patient having contraindications to Propofol, opioids and their antidotes;
2. Patients who have received propofol for more than 3 days in the ICU or in the general ward before being transferred to the ICU before signing informed consent form;

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

   1. Cardiovascular system: New York Heart Association (NYHA) Class III and IV heart failure, Adams-stokes syndrome; acute coronary syndrome (ACS) that occurs within 6 months before screening; bradycardia requiring medication and/or heart rate ≤ 50 beats/min; a history of severe arrhythmia such as II-III degree atrioventricular block (excluding patients using pacemakers); acute and chronic myocarditis;
   2. Patients with hyperlipidemia: Defined as patients with TC ≥ 5.2 mmol/L or LDL-C ≥ 3.4 mmol/L at screening, or patients with severely increased blood pressure or blood glucose despite their blood lipid levels meeting the requirements, rendering the patients huge risk of cardiovascular diseases per the investigator's judgment; patients with acute pancreatitis;
   3. Patients with mental diseases (e.g., schizophrenia, depression) and cognitive dysfunction; grand mal epilepsy and convulsion; head injury, intracranial hypertension, cerebral aneurysm; Glasgow Coma Score (GCS) ≤ 12; SOFA Score > 9; past history of psychotropic and narcotic drug abuse; history of alcohol abuse within 3 months before screening; long-term use of psychotropic drugs;
   4. Patients with high paraplegia and general paralysis; patients with unstable hemodynamics;
   5. Severe hepatic and renal insufficiency (liver function: refer to child-pugh grade C; renal function: glomerular filtration rate eGFR ≤ 30 mL/(min•1.73 m2) [eGFR is 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;
   6. Patients with an expected survival of less than 1 week;
   7. Other situations unsuitable for enrollment per the investigator's consideration.
4. Pregnant or breastfeeding females: women or men of child-bearing potential who are unwilling to use contraception during the trial; subjects who are planning pregnancy within 1 month after the trial starts (including male subjects);
5. Have participated in any other clinical trials within 1 month prior to screening;
6. Other conditions that patients are judged by the investigator to be unsuitable for participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Propofol	Drug: Propofol; Loading Dose：0.5 mg/kg，Maintenance Dose：Maintenance is started at1.5 mg/kg/h, and the dose can be adjusted up and down by 0.25-0.5mg/kg/h.
EXPERIMENTAL: HSK3486	Drug: HSK3486; Loading Dose：0.1 mg/kg，Maintenance Dose：Maintenance is started at 0.3 mg/kg/h, and the dose can be adjusted up and down by 0.05-0.1 mg/kg/h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean duration of qualified sedation	the mean duration of RASS being in the range of -1 to -2 per hour during the study medication provided that no remedial medication is used	Within 96hours of administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recovery	the time for the subject to recover from sedation to full recovery of consciousness (RASS ≥ 0) after discontinuation of drug administration.	Within 24 hours after administration
Time to extubation	the time from intubation (applicable to patients who undergoes intubation after entering the ICU)/ICU admission (applicable to patients with intubation before entering the ICU) to extubation or the time from drug discontinuation to extubation	Within 24 hours after administration

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 9, 2021
• Primary Completion (ACTUAL): August 28, 2021
• Study Completion (ACTUAL): October 9, 2021

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (ACTUAL): December 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 25, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: HSK3486-206

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No