To Evaluate the Efficacy and Safety of HRS-9190 for Injection in Tracheal Intubation During Induction and Skeletal Muscle Relaxation During Maintenance of General Anesthesia in a Multi-center, Randomized, Double-blind, Positive Drug Parallel Controlled Phase III Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- Proportion of participants with excellent or good intubation conditions at the time of tracheal intubation
研究概览
简要总结
A multicenter, randomized, double - blind, placebo - controlled, parallel - group phase III clinical trial was carried out to evaluate the efficacy and safety of HRS - 9190 for skeletal muscle relaxation during tracheal intubation in the induction and maintenance phases of general anesthesia. The primary objective was to evaluate the effectiveness of HRS - 9190 in achieving skeletal muscle relaxation during tracheal intubation in the induction and maintenance phases of general anesthesia. The secondary objective was to assess the safety and pharmacokinetic profile of HRS - 9190.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Independent dispensing personnel were designated to conduct the trial, and both evaluators and participants remained blinded throughout. The trial drug was administered in accordance with the protocol. After blind verification, data were locked; the statistician then submitted an unblinding request. Specifically, the randomization and drug assignment codes were disclosed only to authorized statistical personnel to enable full analysis. Double-blinding was maintained unless broken for urgent clinical reasons-e.g. , serious adverse events or life-threatening emergencies-upon investigator decision, following immediate notification to the monitor, principal investigator, and sponsor. Unblinding authorization was pre-registered in the RTSM system. Once unblinded, the participant was classified as discontinued.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign ICF before starting trial-related activities, fully understand the purpose and significance of this trial, and voluntarily abide by the process of this trial;
- •For elective surgery, tracheal intubation should be performed under general anesthesia and intermittent drug administration is suitable for intraoperative muscle relaxation maintenance, and the operation time is expected to be 1.5-4 hours; 3.18 years old ≤ age ≤75 years old, regardless of gender;
- •4. 18.0 kg/m2≤ body mass index (BMI) ≤28.0 kg/m2;
- •ASA grade I-II;
- •Female participants of childbearing potential must agree to use highly effective contraception with their partner and avoid egg donation from the time they sign the ICF until 1 month after the last dose of the investigational drug, have a negative serum pregnancy test during the screening period, and are not lactating; Men whose partner was a woman of childbearing potential agreed to use highly effective contraception with their partner and to avoid sperm donation from the time they signed the ICF until 1 month after the last dose of the investigational product.
排除标准
- •previous neuromuscular diseases: myasthenia gravis, myasthenic syndromes, myotonic disorders, poliomyelitis, etc. Previous immune diseases requiring long-term steroid therapy (3 months or more);
- •a history of myocardial infarction or unstable angina, a history of severe arrhythmia such as atrioventricular block degree II or higher, or a history of New York Heart Association (NYHA) functional class II or higher within 6 months before screening that was deemed by the investigator to increase the risk of sedation/anesthesia; Participants with hypertension or hypotension who had poorly controlled blood pressure (systolic blood pressure ≥160 mmHg or ≤90 mmHg at screening; and/or diastolic blood pressure ≥100 mmHg or ≤60 mmHg at screening); Previous history of ischemic stroke or transient ischemic attack (TIA); Participants with psychiatric disorders (e.g., schizophrenia, depression, etc.) and cognitive impairment, or a history of epilepsy, or previous history of psychotropic or narcotic drug abuse;
- •The presence of severe respiratory diseases such as chronic obstructive pulmonary disease or bronchial asthma; Or those with obstructive sleep apnea syndrome, as assessed by investigators, who might be at risk for difficult intubation;
- •abnormal body temperature >37.5℃ or <36℃ during the screening period; He had a history of malignant high fever. Hypothermia surgery was planned.
- •having a history of drug, drug, or alcohol abuse within 1 year before randomization
- •QTc (QTcF= QT/RR0.33) : male >450 ms, female >470 ms;
- •Abnormal liver function during screening: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥1.5 times upper limit of normal (ULN) and/or total bilirubin (TBIL) ≥1.5 times ULN; Abnormal renal function during screening: serum creatinine (Cr) ≥1.5 times upper limit of normal (ULN); Serum albumin (ALB) during screening was less than 35g/L;
- •electrolyte disturbance or known dehydration, acid/alkalosis, hypercapnia, or other factors assessed by the investigator during the screening period;
- •positive for human immunodeficiency virus (HIV) antibody, syphilis antibody, hepatitis B surface antigen, and hepatitis C virus (HCV) antibody;
- •previous allergy to neuromuscular blocking drugs or other drugs that may be used during the trial;
- •use other drugs that affect the effect of muscle relaxant, and the interval between the last use and the random time is less than 5 half-lives (according to the actual drug instructions, the half-life is unknown, then the elution is according to 48 hours) : Neuromuscular blockers, cholinesterase inhibitors or cholinergic drugs, monoamine oxidase inhibitors, antibiotics, diuretics, antiarrhythmic drugs and local anesthetics, anticonvulsants and psychotropic drugs; Other
- •participated in another drug (defined as receipt of a trial drug or placebo) or device clinical trial within 3 months before screening;
- •other circumstances that the investigator judged the participant to be ineligible for participation in the trial.
研究组 & 干预措施
HRS-9190 group
干预措施: Administration of intravenous HRS-9190 (Drug)
Control group
干预措施: Administration of intravenous rocuronium (Drug)
结局指标
主要结局
Proportion of participants with excellent or good intubation conditions at the time of tracheal intubation
时间窗: From the beginning of the drug to 5 minutes after the administration
Cooper score evaluation of tracheal intubation conditions: excellent, 8 - 9 points; good, 6 - 7 points; fair, 3 - 5 points; poor, 0 - 2 points.
次要结局
- Time from last dose to extubation(Perioperative)
- Time (minutes) required for the recovery of the myotwitch height value (T1) from 25% until the Train-of-Four ratio (TOFr) reaches ≥90%(During the last administration to 2 hours after administration, the TOFr of muscle relaxation monitoring was ≥90%)
- Time to complete tracheal intubation(Time to complete tracheal intubation within 5 minutes after the start of drug administration)
- Time to onset(The time to achieve T1% maximal inhibition was monitored with a muscle relaxometer from the beginning of the dose until 5 min after the dose)
- Action time(Perioperative)
- Percentage of time T1%≤25%(Perioperative)
- Anesthesiologist satisfaction score(From the beginning of administration to 1 hour after the end of surgery)
- Surgeon satisfaction score(From the beginning of administration to 1 hour after the end of surgery)
研究者
Yingyong Zhou,MD,PhD
Director
The Third Xiangya Hospital of Central South University