Clinical trial NCT04147416: A Study Evaluating the Efficacy and Safety of HSK3486 for Sedation
Official title: A Multi-center, Open-label, Randomized, Propofol-controlled Study Evaluating the Efficacy and Safety of Intravenous Administration of HSK3486 Injectable Emulsion for Sedation in Intensive Care (ICU) Patients Undergoing Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sedation
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-11-01
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean time to sedation
timeFrame: at day 1
Secondary outcomes:
measure: Study drug use
timeFrame: at day 1
measure: Minimum maintenance dose
timeFrame: at day 1
measure: Unit weight dose of remedial drug
timeFrame: at day 1
measure: Unit weight dose of remifentanil
timeFrame: at day 1
measure: Extubation time
timeFrame: at day 1
measure: Recovery time
timeFrame: at day 1
Other outcomes:
Locations:
city: Guanzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
References:
citation: Liu Y, Yu X, Zhu D, Zeng J, Lin Q, Zang B, Chen C, Liu N, Liu X, Gao W, Guan X. Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial. Chin Med J (Engl). 2022 May 5;135(9):1043-1051. doi: 10.1097/CM9.0000000000001912.