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

• ClinicalTrials.gov Identifier: NCT04620031
• Recruitment Status: Recruiting
• First Posted: November 6, 2020
• Last Update Posted: December 17, 2020
• Sponsor: Haisco Pharmaceutical Group Co., Ltd.
• Information provided by (Responsible Party): Haisco Pharmaceutical Group Co., Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sedation in Intensive Care	Drug: HSK3486; Drug: Propofol	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 8, 2020
• Estimated Primary Completion Date: June 30, 2021
• Estimated Study Completion Date: August 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: HSK3486	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	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

Outcome Measures

Primary Outcome Measures :

1. Success rate of sedation [ Time Frame: 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 :

1. Mean qualified rate of sedation [ Time Frame: 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
2. Use of study drug [ Time Frame: 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
3. Dose of remedial drugs per unit weight [ Time Frame: 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)
4. Time to extubation [ Time Frame: 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
5. Time to recovery [ Time Frame: 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
6. Incidence of adverse events [ Time Frame: From day -1 to 24 hours after administration ]
   safety endpoits

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Liu xiao; 15921176768; liux1@haisco.com

Locations

China

The First Affiliated Hospital of Sun Yat-sen University; Recruiting

Guangzhou, China

Contact: guan xiangdong

Sponsors and Collaborators

Haisco Pharmaceutical Group Co., Ltd.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Haisco Pharmaceutical Group Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04620031
• Other Study ID Numbers: HSK3486-307
• First Posted: November 6, 2020
• Last Update Posted: December 17, 2020
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Propofol; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics