Clinical trial NCT05841667: Impact of CES1 Genotype on Remimazolam
Official title: A Clinical Study to Explore the Effect of Carboxylesterase 1 (CES1) Genotype on Pharmacokinetics, Safety, and Efficacy of Remimazolam
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Adult
Middle Aged
Elective Surgical Procedures
Lead sponsor: Korea University Guro Hospital
Sponsor class: OTHER
First posted: 2023-05-03
Enrollment: 120
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Dose-adjusted steady-state concentration of remimazolam
timeFrame: Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam
measure: Maintenance dose of remimazolam for maintaining general anesthesia
timeFrame: Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam
measure: Total dose of remimazolam used to induce general anesthesia
timeFrame: Initiation of remimazolam administration ~ 5 minutes after start of remimazolam
Secondary outcomes:
measure: Time to LOC after remimazolam administration during anesthesia induction
timeFrame: Initiation of remimazolam administration ~ 5 minutes after start of remimazolam
measure: Time to bispectral index(BIS) < 60 after remimazolam administration during anesthesia induction
timeFrame: Initiation of remimazolam administration ~ 10 minutes after start of remimazolam
measure: Changes in BIS during induction and maintenance of anesthesia
timeFrame: Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam
measure: Percentage maintained BIS >60 during general anesthesia
timeFrame: Initiation of remimazolam administration ~ Cessation of remimazolam(up to 10 hours after start of remimazolam administration)
measure: Changes in BIS during anesthesia induction and maintenance
timeFrame: Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam
measure: Postanesthesia care unit (PACU) length of stay
timeFrame: PACU admission ~ PACU discharge (within 3 hours after PACU admission)
measure: Emergence delirium
timeFrame: Immediately after extubation ~ 3 hours after PACU admission
measure: Resedation
timeFrame: Immediately after extubation ~ 3 hours after PACU admission
measure: Precipitation
timeFrame: Initiation of remimazolam administration ~ 10 minutes after start of remimazolam
measure: Injection pain caused by remimazolam administration
timeFrame: Initiation of remimazolam administration ~ 3 minutes after start of remimazolam
measure: Adverse events up to 48 hours after surgery
timeFrame: Initiation of remimazolam administration ~ 48 hours after surgery
measure: 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)
timeFrame: Immediately before the start of remimazolam ~ 120 minutes after remimazolam cessation
measure: Total dose of remimazolam during general anesthesia
timeFrame: Initiation of remimazolam administration ~ Cessation of remimazolam(up to 10 hours after start of remimazolam administration)
measure: Total dose of remifentanil during general anesthesia
timeFrame: Initiation of remifentanil administration ~ Cessation of remifentanil(up to 10 hours after start of remifentanil administration)
measure: Operation time
timeFrame: Start of surgery ~ End of surgery(up to 10 hours after start of surgery)
measure: Anesthesia time
timeFrame: Initiation of remimazolam administration ~ Exit to the PACU (within 30 minutes after remimazolam cessation)
measure: Flumazenil dosage
timeFrame: Cessation of remimazolam ~ 30 minutes after remimazolam cessation
measure: Pain score in PACU
timeFrame: PACU admission ~ PACU discharge (within 3 hours after PACU admission)
measure: Analgesic usage in PACU
timeFrame: PACU admission ~ PACU discharge (within 3 hours after PACU admission)
measure: Delirium
timeFrame: After surgery ~ Hospital discharge (within 1 month after surgery)
measure: Postoperative complications
timeFrame: After surgery ~ Hospital discharge (within 1 month after surgery)
measure: Hospital stay after surgery
timeFrame: The day of surgery ~ Hospital discharge (within 1 month after surgery)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: Korea University Guro Hospital
name: Byung Gun Lim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: