Laparoscopic SurgeryNCT07620782
Response Surface Modeling of Remimazolam and Sevoflurane
A study testing Remimazolam (Byfavo) and Sevoflurane (Volatile Anesthetic) in people with Laparoscopic Surgery, run by Pusan National University Yangsan Hospital at 1 site in South Korea.
Trial summary
This prospective randomized open-label study aims to investigate the pharmacodynamic interaction between remimazolam and sevoflurane during general anesthesia using response surface modeling. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Laparoscopic Surgery
- What is being tested?
- Remimazolam (Byfavo) and Sevoflurane (Volatile Anesthetic)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteSouth Korea
- Study dates
- 15 May 2026to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Pusan National University Yangsan Hospital
Yangsan, 50612
Hee Young Kim, MD, PhD, 82-55-360-2129, anekhy@gmail.com
About this study
Official title: Response Surface Model Between Remimazolam and Sevoflurane; Comparison of the Minto and the Greco Model
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.
Read the detailed description
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.
- Conditions
- Laparoscopic Surgery
- Being tested
- Remimazolam (Byfavo), Sevoflurane (Volatile Anesthetic)
- Keywords
- general anesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Sevoflurane (Volatile Anesthetic)Drug
Sevoflurane will be administered by inhalation with targeted end-tidal concentrations between 0 and 2 vol%.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Remimazolam (Byfavo); Drug: Sevoflurane (Volatile Anesthetic) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: During anesthetic induction
Secondary outcomes (11)
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.
Measured: During anesthetic induction
Loss of consciousness (LOC)
Time to loss of consciousness during induction
Measured: During anesthetic induction
Recovery of consciousness (ROC)
Time to recovery of consciousness
Measured: During emergence from anesthesia
Heart rate
Heart rate (beats per minute) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Systolic blood pressure
Systolic blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Mean blood pressure
Mean blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Cardiac output
Cardiac output (L/min) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Cardiac index
Cardiac index (L/min/m²) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Stroke volume variation
Stroke volume variation (%) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Pulse pressure variation
Pulse pressure variation (%) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Peripheral oxygen saturation
Peripheral oxygen saturation (%) will be recorded at 5-minute intervals during the intraoperative period.
Measured: Intraoperative period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2026
- Study start15 May 2026
- Primary completion1 Apr 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Laparoscopic SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pusan National University Yangsan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kim Hee Young, Pusan National University Yangsan Hospital
- Investigators
- Hee Young Kim, MD, PhD, Principal investigator, Pusan National University Yangsan Hospital, Yangsan, South Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07620782
- Sponsor's protocol ID
- 05-2023-090
- Status last verified
- May 2026
- First submitted
- 14 May 2026
- Last updated
- 2 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27696490Jeon 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.
PubMed 27482310Byung-Moon Choi: An overview of pharmacodynamic drug interaction with isobole and response surface model in anesthesia. APM 2016; 11: 1-13
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response Surface Model Between Remimazolam and Sevoflurane; Comparison of the Minto and the Greco Model
- ClinicalTrials.gov ID
- NCT07620782
- Acronym / sponsor ID
- 05-2023-090
- Conditions
- Laparoscopic Surgery
- Keywords
- general anesthesia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Pusan National University Yangsan HospitalUniversity, hospital or other
- Study start
- 15 May 2026 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 2 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Remimazolam and Sevoflurane Combination During Anesthetic Induction | Experimental | Drug: Remimazolam (Byfavo), Drug: Sevoflurane (Volatile Anesthetic)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. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remimazolam (Byfavo)Remimazolam will be administered at infusion rates ranging from 0 to 6 mg/kg/h using an infusion pump with pharmacokinetic simulation software. | Drug | Remimazolam and Sevoflurane Combination During Anesthetic Induction |
| Sevoflurane (Volatile Anesthetic)Sevoflurane will be administered by inhalation with targeted end-tidal concentrations between 0 and 2 vol%. | Drug | Remimazolam and Sevoflurane Combination During Anesthetic Induction |
Primary outcome
Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model
Time frame: During anesthetic induction
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.
Interaction parameter between remimazolam and sevoflurane derived from the Greco response surface model
Time frame: During anesthetic induction
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.
11 secondary outcomes
BIS response according to hypnotic combinations
Time frame: During anesthetic induction
Loss of consciousness (LOC)
Time frame: During anesthetic induction
Recovery of consciousness (ROC)
Time frame: During emergence from anesthesia
Heart rate
Time frame: Intraoperative period
Systolic blood pressure
Time frame: Intraoperative period
Mean blood pressure
Time frame: Intraoperative period
Cardiac output
Time frame: Intraoperative period
Cardiac index
Time frame: Intraoperative period
Stroke volume variation
Time frame: Intraoperative period
Pulse pressure variation
Time frame: Intraoperative period
Peripheral oxygen saturation
Time frame: Intraoperative period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Background: PubMed 27696490Choe 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.
- Background: PubMed 27482310Jeon 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.
- BackgroundByung-Moon Choi: An overview of pharmacodynamic drug interaction with isobole and response surface model in anesthesia. APM 2016; 11: 1-13
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hee Young Kim, MD, PhD principal investigator
Pusan National University Yangsan Hospital, Yangsan, South Korea
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remimazolam (Byfavo) and Sevoflurane (Volatile Anesthetic) in people with Laparoscopic Surgery, run by Pusan National University Yangsan Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hee Young Kim, MD, PhD (82-55-360-2129, anekhy@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model (time frame: During anesthetic induction). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07620782, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.