Efficacy and Safety of HRS-9190 in General Anesthesia

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Administration of intravenous HRS-9190
  During the induction phase, 0.6 mg/kg of HRS-9190 was administered intravenously, and during the maintenance phase, 0.2 mg/kg of HRS-9190 was administered intravenously.
• Препарат Administration of intravenous rocuronium
  During the induction phase, 0.6 mg/kg of rocuronium was administered intravenously, and during the maintenance phase, 0.15 mg/kg of rocuronium was administered intravenously.

Первичные конечные точки

• Proportion of participants with excellent or good intubation conditions at the time of tracheal intubation [Срок оценки: From the beginning of the drug to 5 minutes after the administration]

Вторичные конечные точки (8)

• Time (minutes) required for the recovery of the myotwitch height value (T1) from 25% until the Train-of-Four ratio (TOFr) reaches ≥90% [Срок оценки: During the last administration to 2 hours after administration, the TOFr of muscle relaxation monitoring was ≥90%]
• Time to complete tracheal intubation [Срок оценки: Time to complete tracheal intubation within 5 minutes after the start of drug administration]
• Time to onset [Срок оценки: 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 [Срок оценки: Perioperative]
• Percentage of time T1%≤25% [Срок оценки: Perioperative]
• Time from last dose to extubation [Срок оценки: Perioperative]
• Anesthesiologist satisfaction score [Срок оценки: From the beginning of administration to 1 hour after the end of surgery]
• Surgeon satisfaction score [Срок оценки: From the beginning of administration to 1 hour after the end of surgery]

Критерии участия

Критерии включения

• 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; 5. ASA grade I-II; 6. 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Third Xiangya Hospital of Central South University, Changsha, hunan — Чанша

Идентификаторы

NCT: NCT07733245 · HRS-9190-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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