Response Surface Modeling of Remimazolam and Sevoflurane

NCT07620782 | Recruiting

• 1 other identifier: 05-2023-090
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Laparoscopic Surgery

Keywords

general anesthesia

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  During anesthetic induction

Secondary Outcomes (11)

• BIS response according to hypnotic combinations

  During anesthetic induction

• Loss of consciousness (LOC)

  During anesthetic induction

• Recovery of consciousness (ROC)

  During emergence from anesthesia

• Heart rate

  Intraoperative period

• Systolic blood pressure

  Intraoperative period

Study Arms (1)

Remimazolam and Sevoflurane Combination During Anesthetic Induction

EXPERIMENTAL

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)

Interventions

Remimazolam (Byfavo) DRUG

Remimazolam will be administered at infusion rates ranging from 0 to 6 mg/kg/h using an infusion pump with pharmacokinetic simulation software.

Remimazolam and Sevoflurane Combination During Anesthetic Induction

Sevoflurane (Volatile Anesthetic) DRUG

Sevoflurane will be administered by inhalation with targeted end-tidal concentrations between 0 and 2 vol%.

Remimazolam and Sevoflurane Combination During Anesthetic Induction

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 20 to 80 years
• Scheduled for elective surgery under general anesthesia at Pusan National University Yangsan Hospital
• American Society of Anesthesiologists (ASA) physical status I or II
• Able to provide written informed consent

You may not qualify if:

• Known allergy to remimazolam or sevoflurane
• Renal, hepatic, neuromuscular, or neurological disease
• Use of medications affecting the central nervous system
• Chronic psychoactive drug use
• Ischemic heart disease
• Pregnant women

Sponsors & Collaborators

• Pusan National University Yangsan Hospital: lead

Study Sites (1)

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

RECRUITING

Related Publications (3)

• Choe S, Choi BM, Lee YH, Lee SH, Lee EK, Kim KS, Noh GJ. Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia. Clin Exp Pharmacol Physiol. 2017 Jan;44(1):30-40. doi: 10.1111/1440-1681.12677.

  PMID: 27696490 BACKGROUND

• Jeon S, Kwon JY, Kim HK, Kim TK. Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models. Korean J Anesthesiol. 2016 Aug;69(4):341-9. doi: 10.4097/kjae.2016.69.4.341. Epub 2016 Jun 22.

  PMID: 27482310 BACKGROUND

• Byung-Moon Choi: An overview of pharmacodynamic drug interaction with isobole and response surface model in anesthesia. APM 2016; 11: 1-13

  BACKGROUND

MeSH Terms

Interventions

remimazolam; Sevoflurane

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons

Study Officials

• Hee Young Kim, MD, PhD

  Pusan National University Yangsan Hospital, Yangsan, South Korea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hee Young Kim, MD, PhD

CONTACT

82-55-360-2129; anekhy@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor for fund

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: June 2, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)