An interventional study of Remimazolam (Byfavo) and Sevoflurane (Volatile Anesthetic) in Laparoscopic Surgery, sponsored by Pusan National University Yangsan Hospital. Recruiting at 1 site in South Korea. Open to participants aged 20 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-06-02.
Sponsored by Pusan National University Yangsan Hospital · Not applicable, Interventional, and Basic science
This prospective randomized open-label study aims to investigate the pharmacodynamic interaction between remimazolam and sevoflurane during general anesthesia using response surface modeling. Although remimazolam has favorable hemodynamic stability compared with propofol, its hypnotic effect may be less predictable and poorly correlated with conventional sedation monitoring indices such as the bispectral index (BIS). In clinical practice, remimazolam and sevoflurane are often combined during induction and maintenance of anesthesia; however, the optimal interaction between these agents remains unclear.
This study will evaluate whether the interaction between remimazolam and sevoflurane is synergistic, additive, or infra-additive using two representative response surface interaction models: the Minto model and the Greco model. BIS values and predicted effect-site concentrations will be analyzed using NONMEM software.
Remimazolam is a recently developed ultra-short-acting benzodiazepine anesthetic with favorable pharmacokinetic characteristics, including a short context-sensitive decrement time and relatively stable hemodynamics. Despite these advantages, remimazolam may exhibit weaker hypnotic potency and inconsistent correlations with conventional anesthetic depth monitors such as BIS.
In current clinical practice, anesthesiologists frequently combine remimazolam with volatile anesthetics such as sevoflurane during induction or maintenance of anesthesia. However, the pharmacodynamic interaction between remimazolam and sevoflurane has not been fully elucidated.
The present study will investigate the interaction between remimazolam and sevoflurane using response surface modeling. The study will enroll adult patients undergoing elective laparoscopic surgery under general anesthesia. Various combinations of remimazolam infusion rates and end-tidal sevoflurane concentrations will be administered during anesthetic induction. BIS values and predicted effect-site concentrations will be collected and analyzed.
Pharmacodynamic interaction analyses will be performed using NONMEM nonlinear mixed-effects modeling software. Both the Minto interaction model and the Greco interaction model will be applied to determine whether the interaction between remimazolam and sevoflurane is synergistic, additive, or infra-additive.
Pusan National University Yangsan Hospital is the lead sponsor of 108 studies on the registry; 27 are open to participants now.
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The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants undergoing elective surgery under general anesthesia will receive varying combinations of remimazolam and sevoflurane during anesthetic induction to evaluate pharmacodynamic interactions using response surface modeling.
Drug: Remimazolam (Byfavo) · Drug: Sevoflurane (Volatile Anesthetic)
Remimazolam will be administered at infusion rates ranging from 0 to 6 mg/kg/h using an infusion pump with pharmacokinetic simulation software.
Sevoflurane will be administered by inhalation with targeted end-tidal concentrations between 0 and 2 vol%.
Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model
The interaction coefficient (α) describing the pharmacodynamic interaction between remimazolam effect-site concentration and end-tidal sevoflurane concentration will be estimated using the Minto response surface model based on BIS values collected during anesthetic induction.
Time frame: During anesthetic induction
Interaction parameter between remimazolam and sevoflurane derived from the Greco response surface model
The pharmacodynamic interaction parameter describing the interaction between remimazolam effect-site concentration and end-tidal sevoflurane concentration will be estimated using the Greco response surface model based on BIS values collected during anesthetic induction.
Time frame: During anesthetic induction
BIS response according to hypnotic combinations
Bispectral Index (BIS) values will be continuously recorded during anesthetic induction according to predefined combinations of remimazolam effect-site concentration and end-tidal sevoflurane concentration. The BIS is a processed electroencephalographic monitoring scale ranging from 0 to 100, where lower values indicate deeper levels of hypnosis and higher values indicate lighter levels of sedation or consciousness.
Time frame: During anesthetic induction
Loss of consciousness (LOC)
Time to loss of consciousness during induction
Time frame: During anesthetic induction
Recovery of consciousness (ROC)
Time to recovery of consciousness
Time frame: During emergence from anesthesia
Heart rate
Heart rate (beats per minute) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Systolic blood pressure
Systolic blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Mean blood pressure
Mean blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Cardiac output
Cardiac output (L/min) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Cardiac index
Cardiac index (L/min/m²) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Stroke volume variation
Stroke volume variation (%) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Pulse pressure variation
Pulse pressure variation (%) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Peripheral oxygen saturation
Peripheral oxygen saturation (%) will be recorded at 5-minute intervals during the intraoperative period.
Time frame: Intraoperative period
Plan to share: No
Started May 2026 (actual). Primary completion is estimated for Apr 2027, 10 months after the start.
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Studies of the drugs tested here: Remimazolam besilate · Sevoflurane
Pusan National University Yangsan Hospital →