A Study Evaluating Sedation of Intravenous Administration of HSK3486 Injectable Emulsion in ICU Patients Undergoing Mechanical Ventilation

A Multi-Center, Randomized, Single-Blind, Propofol-Controlled Phase III Clinical Study Evaluating Sedation of Intravenous Administration of HSK3486 Injectable Emulsion in ICU Patients Undergoing Mechanical Ventilation

This is a multi-center, randomized, single-blind, propofol-controlled phase III clinical study. In this study, ICU patients undergoing mechanical ventilation are expected to be enrolled and will be randomly assigned to the HSK3486 group and the propofol group.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangzhou, China
    • The First Affiliated Hospital of Sun Yat-sen 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 are expected to require 6-24 h of sedation after randomization;
2. The target RASS for the required sedation of patients ranges from +1 to -2 points;
3. Aged ≥ 18 and < 80 years old, with no gender requirement;
4. 18 kg/m2 ≤ BMI ≤ 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 sedation 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; patients who require vasoactive drugs to maintain a normal blood pressure;
   2. Patients with mental system disorders (such as schizophrenia, depression, etc.) and cognitive disorders; patients with a history of abuse of psychotropic drugs and anesthetics; patients with a history of alcohol abuse within 3 months prior to screening; patients with a history of drug abuse; patients with a history of long-term use of psychotropic drugs, etc.;
   3. Severe hepatic and renal insufficiency (liver function: refer to child-pugh grade C, the scale is shown in Appendix 6; 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;
   4. Grand mal epilepsy and convulsion; craniocerebral injury, intracranial hypertension, cerebral aneurysm; a Glasgow coma scale (GCS) of ≤ 12 points (see Appendix 4 for the scale); a SOFA scale of > 9 points (see Appendix 5 for the scale); patients with high paraplegia and general paralysis;
   5. Expected survival of ≤ 72 h.
4. Pregnant or lactating females; women or men of child-bearing potential who are unwilling to use contraception through the study; subjects who are planning pregnancy within 1 month after the study (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 Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSK3486; HSK3486 for Sedation	Drug: HSK3486; Loading Dose：0.1 mg/kg, infused with 4 min ± 30 s； 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. Range of maintenance dose: 0.06-0.8 mg/kg/h
Active Comparator: Propofol; Propofol for Sedation	Drug: Propofol; Loading Dose：0.5 mg/kg, infused with 4 min ± 30 s Maintenance Dose：Maintenance is started at 1.5 mg/kg/h, and the dose can be adjusted up and down by 0.25-0.5 mg/kg/h. Range of maintenance dose: 0.3-4 mg/kg/h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate of sedation	1) The time period during which the RASS is in the range of +1 to -2 accounts for ≥ 70% of the total duration of study administration and 2) Remedial treatment is not used.	Within 24 hours of administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Mean qualified rate of sedation	Defined as the percentage of time period during which the RASS is in the range of +1 to -2 relative to the total duration of study administration	Within 24 hours of administration
Use of study drug	the loading doses of HSK3486 and propofol, mean maintenance dose and total dose per unit weight per hour of HSK3486 or propofol, and the number of dose modifications and the number of top up doses during the maintenance period	Within 24 hours of administration
Dose of remedial drugs per unit weight	the mean dose per unit weight per hour of other sedatives used to maintain the target sedation (RASS within +1 to -2 points)	Within 24 hours of administration
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
Incidence of adverse events	safety endpoits	From day -1 to 24 hours after administration

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Publications and helpful links

General Publications

• Liu Y, Chen C, Liu N, Tong L, Nie Y, Wu J, Liu X, Gao W, Tang L, Guan X. Efficacy and Safety of Ciprofol Sedation in ICU Patients with Mechanical Ventilation: A Clinical Trial Study Protocol. Adv Ther. 2021 Oct;38(10):5412-5423. doi: 10.1007/s12325-021-01877-6. Epub 2021 Aug 21.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): June 2, 2021
• Study Completion (Actual): August 17, 2021

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 6, 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: HSK3486-307

Drug and device information, study documents

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