Impact of CES1 Genotype on Remimazolam

Korea University

Status: Enrolling

Conditions: Middle Aged; Adult; Elective Surgical Procedures

Treatments: Drug: Remimazolam besylate

Study type: Observational

Funder types: Other

Identifiers

NCT05841667

2023GR0069

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 19 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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

Trial design

120 participants in 1 patient group

CES1 without or without single nucleotide polymorphism (SNP)

Description:

We will determine the CES1 genotype of participants through a laboratory test. Several different types of SNPs can be identified, and analyses can be further stratified by CES1 SNP type.

Treatment:

Drug: Remimazolam besylate