Efficacy and Safety of Eleveld PK/PD Model-based Dosing During General Anesthesia

Phase 4Not Yet RecruitingNCT07675850

Seoul National University Hospital68 enrolled

Overview

The goal of this randomized, controlled clinical trial is to evaluate the efficacy, safety, and recovery profile of an individualized, Eleveld pharmacokinetic/pharmacodynamic model-guided dosing strategy for remimazolam in adult patients undergoing elective non-cardiac surgery under general anesthesia. The main questions it aims to answer are: Does Eleveld model-guided customized dosing significantly reduce the eye-opening time at the end of surgery compared to standard weight-based dosing? Can the Eleveld model-guided approach prevent relative drug accumulation and delayed emergence while maintaining an adequate depth of anesthesia and comparable hemodynamic stability? Researchers will compare the Experimental Group (Eleveld model-guided dosing) to the Control Group (Standard weight-based label dosing) to see if preemptive dose optimization based on individual patient covariates effectively reduces the total drug consumption, frequency of rescue flumazenil administration, and emergence time. Participants will: * Be randomly assigned to receive remimazolam for the induction and maintenance of general anesthesia according to either the Eleveld model-guided customized regimen or the standard weight-based regimen. * Have their depth of anesthesia continuously monitored using a Bispectral Index (BIS) sensor. * Be assessed for the primary outcome (time to eye-opening upon verbal command after discontinuation of anesthetics) and secondary outcomes, including total drug consumption, hemodynamic stability, and postoperative complications (e.g., re-sedation, delirium, PONV).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 19 YearsMax age: 79 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients aged 19 to 79 years undergoing elective non-cardiac surgery expected to last 60 minutes or longer under general anesthesia with endotracheal intubation Exclusion Criteria: * Emergency surgery * Surgery requiring evoked potential (EP) monitoring * Chronic benzodiazepine users * Body Mass Index (BMI) ≥ 35 kg/㎡ * Chronic kidney disease * Hepatic dysfunction or chronic liver disease * Contraindication or history of hypersensitivity to remimazolam * American Society of Anesthesiologists (ASA) physical status ≥ IV * Pregnant women * Contraindication or history of hypersensitivity to flumazenil

Outcomes

Primary Outcomes

Eye-Opening Time, EOT

Time frame: Time from the discontinuation of remimazolam to eye-opening upon verbal command (min), up to 1h

Secondary Outcomes

Time to loss of consciousness (LOC)

Time frame: Time from the start of remimazolam administration to loss of consciousness (min), up to 1h

Intraoperative Bispectral Index (BIS) values

Time frame: Perioperative/Periprocedural

Incidence of intraoperative bradycardia (heart rate < 45 bpm)

Time frame: Perioperative/Periprocedural

Incidence of intraoperative tachycardia (heart rate > 110)

Time frame: Perioperative/Periprocedural

Incidence of intraoperative hypotension (mean blood pressure < 65 mmHg)

Time frame: Perioperative/Periprocedural

Incidence of intraoperative hypertension (SBP > 140 mmHg)

Time frame: Perioperative/Periprocedural

Total dose of intraoperative remimazolam (mg)

Time frame: Perioperative/Periprocedural

Total dose of intraoperative remifentanil (㎍)

Time frame: Perioperative/Periprocedural

Total dose(s) of intraoperative vasopressor(s)

Ephedrine (mg)

Time frame: Perioperative/Periprocedural

Extubation time (min)

Time frame: Time from the discontinuation of remimazolam to the removal of the endotracheal tube, up to 1h

Incidence of flumazenil administration

Time frame: From discontinuation of remimazolam to patient discharge from the operating room, up to 1h

Incidence of rescue sevoflurane use

Time frame: Perioperative/Periprocedural

Incidence of oxygen supplementation in the Post-Anesthesia Care Unit (PACU)

Time frame: Perioperative/Periprocedural, on the day of surgery

Incidence of postoperative delirium

Time frame: Perioperative/Periprocedural, up to 1 week

Incidence of postoperative nausea and vomiting (PONV)

Time frame: Perioperative/Periprocedural, up to 1 week

Length of stay in the PACU (min)

Time frame: Perioperative/Periprocedural, on the day of surgery

Incidence of re-sedation

Drop in the Modified Observer's Assessment of Alertness/Sedation \[MOAA/S\] score to 3 or lower during the PACU stay

Time frame: Perioperative/Periprocedural, on the day of surgery

Incidence of intraoperative awareness

assessed using the Modified Brice Questionnaire

Time frame: Perioperative/Periprocedural

Total dose(s) of intraoperative vasopressor(s)

phenylephrine (㎍)

Time frame: Perioperative/Periprocedural

Total dose(s) of intraoperative vasopressor(s)

norepinephrine (㎍)

Time frame: Perioperative/Periprocedural

Efficacy and Safety of Eleveld PK/PD Model-based Dosing During General Anesthesia

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts