Impact of CES1 Genotype on Remimazolam

NCT05841667 | Recruiting

• 1 other identifier: 2023GR0069
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adult; Middle Aged; Elective Surgical Procedures

Outcome Measures

Primary Outcomes (3)

• Dose-adjusted steady-state concentration of remimazolam

  Determine the dose-adjusted steady-state concentration of remimazolam using Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS)

  Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam

• Maintenance dose of remimazolam for maintaining general anesthesia

  Hourly maintenance dose of remimazolam for maintaining general anesthesia

  Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam

• Total dose of remimazolam used to induce general anesthesia

  Determine the total dose of remimazolam to achieve loss of consciousness (LOC). Modified Observer's Alertness/Sedation Scale (MOAA/S) \<2 indicates LOC. The MOAA/S scale assesses a patient's level of alertness and response to stimulation, and is scored on a 6-point scale (6: awake and alert, 1: deeply asleep and unresponsive to any stimulus).

  Initiation of remimazolam administration ~ 5 minutes after start of remimazolam

Secondary Outcomes (22)

• Time to LOC after remimazolam administration during anesthesia induction

  Initiation of remimazolam administration ~ 5 minutes after start of remimazolam

• Time to bispectral index(BIS) < 60 after remimazolam administration during anesthesia induction

  Initiation of remimazolam administration ~ 10 minutes after start of remimazolam

• Changes in BIS during induction and maintenance of anesthesia

  Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam

• Percentage maintained BIS >60 during general anesthesia

  Initiation of remimazolam administration ~ Cessation of remimazolam(up to 10 hours after start of remimazolam administration)

• Changes in BIS during anesthesia induction and maintenance

  Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam

Study Arms (1)

CES1 without or without single nucleotide polymorphism (SNP)

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.

Drug: Remimazolam besylate

Interventions

Remimazolam besylate DRUG

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 without a change in concentration, (3) immediately before discontinuation of remimazolam if there has been a change in concentration since the second blood draw, (4) within 5 minutes of discontinuation, (5) within 15-60 minutes of discontinuation, and (6) 90 minutes after discontinuation. Urine will also be collected after the end of anesthesia to check for metabolites of remimazolam.

CES1 without or without single nucleotide polymorphism (SNP)

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will be conducted on adult patients aged 19-70 years, ASA physical status 1-2, undergoing elective surgery in the operating room of Korea University Guro Hospital.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Korea University Guro Hospital: lead

Study Sites (1)

Korea University Guro Hospital

Seoul, 08308, South Korea

RECRUITING

Study Officials

• Byung Gun Lim, MD, PhD

  Korea University Guro Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Byung Gun Lim, MD, PhD

CONTACT

82-2-2626-1437; bglim9205@korea.ac.kr

Hye Bin Kim, MD, PhD

CONTACT

82-10-9183-5617; aneshbkim@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 10, 2023
• First Posted: May 3, 2023
• Study Start: September 6, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)