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

Phase 3

Completed

• Conditions: Sedation in Intensive Care
• Interventions: Drug: HSK3486; Drug: Propofol

• Registration Number: NCT04620031
• Lead Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-11-03
• Study First Posted: 2020-11-06
• Study Start: 2020-12-08
• Primary Completion: 2021-06-02
• Study Completion: 2021-08-17
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-25
• Last Update Posted: 2022-05-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 135

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HSK3486	HSK3486	HSK3486 for Sedation
Propofol	Propofol	Propofol for Sedation

Primary Outcome Measures

Name	Time	Method
Success rate of sedation	Within 24 hours of administration	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.

Secondary Outcome Measures

Name	Time	Method
Time to recovery	Within 24 hours after administration	the time for the subject to recover from sedation to full recovery of consciousness (RASS ≥ 0) after discontinuation of drug administration
Mean qualified rate of sedation	Within 24 hours of administration	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
Use of study drug	Within 24 hours of administration	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
Dose of remedial drugs per unit weight	Within 24 hours of administration	the mean dose per unit weight per hour of other sedatives used to maintain the target sedation (RASS within +1 to -2 points)
Time to extubation	Within 24 hours after administration	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
Incidence of adverse events	From day -1 to 24 hours after administration	safety endpoits

Trial Locations

Locations (1)

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, China