Impact of CES1 Genotype on Remimazolam

Официальное название

A Clinical Study to Explore the Effect of Carboxylesterase 1 (CES1) Genotype on Pharmacokinetics, Safety, and Efficacy of Remimazolam

Обзор

Remimazolam is primarily metabolized via CES1, and other drugs that are commonly metabolized by CES1 are known to have their pharmacokinetics and clinical effects affected by genetic polymorphisms in CES1. The goal of this observational study is to investigate the impact of the CES1 genotype on the pharmacokinetics, safety, and efficacy of remimazolam in patients undergoing elective surgery.

Вмешательства

• Препарат Remimazolam besylate
  This is an observational study, meaning that no interventions are actually administered to the participants. However, blood and urine samples will be collected for research purposes. Participants will receive remimazolam besylate for at least 2 hours during anesthesia and surgery. Blood will be drawn to determine the concentration of remimazolam in the blood at the following time points: (1) before remimazolam administration, (2) after remimazolam administration has lasted at least 2 hours with

Первичные конечные точки

• Dose-adjusted steady-state concentration of remimazolam [Срок оценки: Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam]
• Maintenance dose of remimazolam for maintaining general anesthesia [Срок оценки: Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam]
• Total dose of remimazolam used to induce general anesthesia [Срок оценки: Initiation of remimazolam administration ~ 5 minutes after start of remimazolam]

Вторичные конечные точки (12)

• Time to LOC after remimazolam administration during anesthesia induction [Срок оценки: Initiation of remimazolam administration ~ 5 minutes after start of remimazolam]
• Time to bispectral index(BIS) < 60 after remimazolam administration during anesthesia induction [Срок оценки: Initiation of remimazolam administration ~ 10 minutes after start of remimazolam]
• Changes in BIS during induction and maintenance of anesthesia [Срок оценки: Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam]
• Percentage maintained BIS >60 during general anesthesia [Срок оценки: Initiation of remimazolam administration ~ Cessation of remimazolam(up to 10 hours after start of remimazolam administration)]
• Changes in BIS during anesthesia induction and maintenance [Срок оценки: Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam]
• Postanesthesia care unit (PACU) length of stay [Срок оценки: PACU admission ~ PACU discharge (within 3 hours after PACU admission)]
• Emergence delirium [Срок оценки: Immediately after extubation ~ 3 hours after PACU admission]
• Resedation [Срок оценки: Immediately after extubation ~ 3 hours after PACU admission]
• Precipitation [Срок оценки: Initiation of remimazolam administration ~ 10 minutes after start of remimazolam]
• Injection pain caused by remimazolam administration [Срок оценки: Initiation of remimazolam administration ~ 3 minutes after start of remimazolam]
• Adverse events up to 48 hours after surgery [Срок оценки: Initiation of remimazolam administration ~ 48 hours after surgery]
• Endogenous metabolites that occur as remimazolam is metabolized in the body (This is an exploratory check, meaning we do not know in advance what substances will be found) [Срок оценки: Immediately before the start of remimazolam ~ 120 minutes after remimazolam cessation]

Критерии участия

Критерии включения

• American Society of Anesthesiologists (ASA) physical status 1 or 2
• Age 19-70 years
• Elective surgery

Критерии исключения

• Concomitant regional anesthesia
• Uncontrolled hypertension (systolic blood pressure >180 mmHg)
• Uncontrolled diabetes mellitus (HbA1c >9.0%)
• Aspartate transaminase (AST), Alanine transferase (ALT), Total bilirubin > more than 2 times the normal upper limit
• Estimated glomerular filtration rate <60 ml/min/1.73m2
• Moderate to severe chronic pulmonary obstructive disease or respiratory failure
• Emergency
• Hepatectomy, Liver transplantation
• Cardiopulmonary bypass use
• Craniotomy due to head trauma, unstable intracranial pressure, or brain disease
• Use of benzodiazepine medications (if tolerance is present)
• Anxiety, alcohol/drug dependence, or addiction to tricyclic antidepressants
• Reported hypersensitivity and adverse reactions to benzodiazepines, flumazenil, and other agents used during anesthesia
• Lactose-related genetic disorders
• Myasthenia gravis or myasthenia gravis syndrome
• Newly diagnosed myocardial infarction/clinically significant coronary artery disease, cerebral ischemic attack/stroke within 6 months, or significant untreated coronary artery disease
• Implanted rate-responsive cardiac pacemaker with a bioelectrical impedance sensor.
• Intrinsic brain disorders or other conditions that make it difficult to determine the depth of anesthesia through EEG measurements (e.g., epilepsy)
• History of severe allergies
• Cognitive impairment that prevents comprehension of the instructions and consent form of this study, in case of sedation
• Expected intraoperative blood loss of 1000 ml or more
• Judged by the investigator to be unsuitable for participation in this study due to other reasons

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

South Korea · 1 центр

• Korea University Guro Hospital — Seoul

Идентификаторы

NCT: NCT05841667 · 2023GR0069

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗