A Study Evaluating the Efficacy and Safety of HSK3486 for Sedation

Phase 2

Completed

• Conditions: Sedation
• Interventions: Drug: HSK3486 0.1-0.2 /0.3 mg / kg group; Drug: Propofol 0.5-1.0/1.5 mg/kg group

• Registration Number: NCT04147416
• Lead Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-30
• Study First Submitted QC: 2019-10-30
• Study First Posted: 2019-11-01
• Study Start: 2019-11-22
• Primary Completion: 2020-05-31
• Study Completion: 2020-07-03
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-25
• Last Update Posted: 2022-05-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HSK3486	HSK3486 0.1-0.2 /0.3 mg / kg group	HSK3486 for Sedation
Propofol	Propofol 0.5-1.0/1.5 mg/kg group	Propofol for Sedation

Primary Outcome Measures

Name	Time	Method
Mean time to sedation	at day 1	Defined as the mean time during which the hourly RASS is in the range of +1- -2 during the study treatment

Secondary Outcome Measures

Name	Time	Method
Unit weight dose of remifentanil	at day 1	Defined as the average hourly unit weight dose of remifentanil for analgesia during the administration period
Recovery time	at day 1	Defined as the time to recover from sedation status to awaken status (RASS ≥ 0) after drug discontinuation, accurate to the minute; if RASS is ≥ 0 at discontinuation, the recovery time is recorded as 0
Minimum maintenance dose	at day 1	Defined as the minimum dose to maintain the target sedation level (RASS between +1 and -2) of the subject for ≥ 2 h and ≥ 4 h during the administration period
Extubation time	at day 1	Defined as the time from ICU admission to extubation (applicable for subjects who have been intubated before admitted to ICU) or the time from intubation to extubation (applicable for subjects who are intubated after admitted to ICU); for withdrawals, the time of extubation is calculated according to the time of discontinuation; if the extubation does not occur within 24 h of administration, the time of extubation is recorded as 24 h
Study drug use	at day 1	Including the loading dose, maintenance dose, additional dose of HSK3486 and propofol, average unit weight dose per hour of HSK3486 or propofol, total and hourly average numbers of dose adjustments
Unit weight dose of remedial drug	at day 1	Defined as the average hourly unit weight dose of sedatives other than propofol administered for maintaining a target sedation level (RASS between +1 and -2) during the administration period

Trial Locations

Locations (1)

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

The First Affiliated Hospital of Sun Yat-sen University

🇨🇳Guanzhou, Guangdong, China