Induction AnesthesiaEarly Phase 1NCT07012902
Relationship Between Remimazolam and Etomidate in Induction of General Anesthesia
A Early Phase 1 study testing Etomidate, Remimazolam and Remimazolam-etomidate in people with Induction Anesthesia and Drug Interactions, run by Second Hospital of Shanxi Medical University at 1 site in China.
Trial summary
In modern anesthesia practice, anesthesiologists often need to choose a combination of multiple drugs according to the specific conditions and surgical needs of patients, which can not only achieve more fine anesthesia management, but also improve perioperative safety and patient comfort. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Induction Anesthesia, Drug Interactions
- What is being tested?
- Etomidate, Remimazolam and Remimazolam-etomidate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 1 siteChina
- Study dates
- 12 Jun 2025to 19 Jul 2025
- Phase
- Early Phase 1
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Both sexes
- aged 18-60 yr
- ASA physical status I-II
- BIM: 18-28kg/m²
Who cannot join
- allergic to remimazolam and etomidate
- in pregnancy or lactation
- serious cardiovascular diseases, long-term alcoholism
- used sedative drugs or opioids within 24 hours
- severe mental illness and myasthenia gravis -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Second Hospital of Shanxi Medical University
Taiyuan, Shanxi, 030001
Zheng Guo M.B.,Ph.D., +863513365790, guozheng713@yahoo.com
About this study
Official title: The Interaction Between Remimazolam and Etomidate During Induction of General Anesthesia Was Studied by Isoradiometric Analysis
In modern anesthesia practice, anesthesiologists often need to choose a combination of multiple drugs according to the specific conditions and surgical needs of patients, which can not only achieve more fine anesthesia management, but also improve perioperative safety and patient comfort. In clinical practice, anesthesiologists will use etomidate combined with a small dose of remimazolam for anesthesia induction to obtain more stable hemodynamics, prevent intraoperative awareness, and relieve anxiety.However, what is the best dose ratio of etomidate combined with remimazolam, the current literature does not give clear indicators.
Read the detailed description
The experiment was divided into two steps. Step 1: Patients were randomly divided into group A (remimazolam induction group) and group B (etomidate induction group) according to the random number table, and group A was selected according to the literature. In group B, the initial dose was 0.2mg/kg, and 0.120mg/kg, and the ratio of successive doses was 1:0.8 and 1: 0.6, the ED50 of group A and group B was calculated by the sequential method, and the calculated remimazolam and etomidate were used as the initial doses of subgroups Step 2: According to the random number table, the patients were divided into group C (0.25ED50 remimazolam +0.75ED50 etomidate), group D (0.5ED50 remimazolam +0.50ED50 etomidate), group E (0.75ED50 remimazolam +0.25ED50 etomidate), and the dose of remimazolam in each group was fixed. The ED50 of etomidate in group C, group D and group E were calculated by sequential method.
Anesthesia methods: One hundred and twenty-five patients of both sexes, aged 18-60 yr, of American Society of Anesthesiologists physical status I-II, BIM: 18-30kg/m2, undergoing general anesthesia in the Second Hospital of Shanxi Medical University, were selected. Before operation, the patients were required to fast and drink, and had not received special preoperative medication. After the patient entered the room, blood pressure, heart rate, oxygen saturation and BIS were monitored and oxygen inhalation was given to the mask for 5L/min. After the tripartite verification was correct, intravenous access was established in the patient's upper limb, fluid infusion was opened, anesthesia was induced, remimazolam and etomidate were injected directly and slowly intravenously, and remimazolam and etomidate were injected for more than 10s according to the dosage of each group. Two drugs were injected at an interval of 10s or more. After the completion of one drug injection, 5ml normal saline was used to flush the tube, and the score was scored 2 minutes after intravenous injection. BIS value of 45-60 was considered as a positive response, and the dose gradient of the next patient was reduced. The observation was calculated as the first patient with positive to negative turning point, and the observation ended when the next patient with positive to negative reaction at the seventh turning point. The secondary outcome measures were the incidence of adverse reactions, changes in heart rate and blood pressure. At the end of the observation, if the patient showed a negative reaction, 0.08mg/kg etomidate was added for sedation, and then sufentanil and rocuronium were given for tracheal intubation in turn, and then surgery was performed.The demographic data of the patients were collected, including: gender, age, height, weight, BIM Statistical methods: probit model was used to calculate ED50 of each group, and the drug correlation coefficient was introduced as 1/(actual dose of remimazolam/ED50 of remimazolam + actual dose of etomidate/ED50 of etomidate). The measurement data with normal distribution were expressed as mean ± standard deviation (x±s). The measurement data with normal distribution between group A and group B were compared by two independent sample t test, and the comparison between group C, group D and group E was compared by one-way analysis of variance. Graphpad prism software was used to make five groups of sequential experimental plots and iso-radiation analysis plots when P<0.05 was considered statistically significant.
- Conditions
- Induction Anesthesia, Drug Interactions
- Being tested
- Etomidate, Remimazolam, Remimazolam-etomidate
- Keywords
- Isoradiation analysis, etomidate, remimazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtomidateDrug
Group A was induced with etomidate, the initial dose was 0.120mg/kg, and the ratio of adjacent doses was 1:0.6
RemimazolamDrug
Group B was induced with remimazolam, the initial dose was 0.20mg/kg, and the ratio of adjacent doses was 1:0.8
Remimazolam-etomidateDrug
In group C, 0.25ED50 remimazolam +0.75ED50 etomidate was used as the initial measurement In group D, 0.5ED50 remimazolam +0.5ED50 etomidate was used as the initial measurement In group E, 0.75ED50 of remimazolam +0.25ED50 of etomidate was used as the initial measurement
| Study group | Role | What they receive |
|---|---|---|
| Group A (remimazolam induction group) | Experimental | The ED50 of group A was calculated by sequential method Receives: Drug: Etomidate |
| Group B (etomidate induction group) | Experimental | The ED50 of group B was calculated by sequential method Receives: Drug: Remimazolam |
| group C (0.25ED50 remimazolam +0.75ED50 etomidate) | Experimental | The ED50 of etomidate in group C were calculated by sequential method. Receives: Drug: Remimazolam-etomidate |
| Group D (0.5ED50 remimazolam +0.5ED50 etomidate) | Experimental | The ED50 of etomidate in group Dwere calculated by sequential method. Receives: Drug: Remimazolam-etomidate |
| Group E (0.75ED50 remimazolam +0.25 etomidate) | Experimental | The ED50 of etomidate in group E were calculated by sequential method. Receives: Drug: Remimazolam-etomidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The ED50 value of etomidate in Group A
The sequential method was used to calculate the median effective dose of etomidate in group A. When the patient's BIS value was between 45 and 60, it was considered a positive response. For the next patient, the dose was reduced by one dose gradient; conversely, if it was a negative response, the dose was increased by one dose gradient. The observation was stopped when the first patient reached the positive-negative turning point, and the next patient with the positive-negative reaction was reached for the seventh turning point. The ED50 of each group was calculated using the probit model.
Measured: one week
The ED50 value of Remimazolam in Group B
The sequential method was used to calculate the median effective dose of remimazolam in group B. A positive reaction was defined as a patient's BIS value ranging from 45 to 60. For the next patient, the dose was reduced by one dose gradient if it was a positive reaction, and increased by one dose gradient if it was a negative reaction. The observation was stopped when the next patient with the 7th positive-negative reaction point was reached. The ED50 of each group was calculated using the probit model.
Measured: one week
Group C D E: etomidate ED50
The sequential method was adopted to calculate the median effective dose of etomidate for groups C, D, and E separately. A patient was considered to have a positive response if their BIS value was between 45 and 60. For the next patient, the dose was reduced by one dose gradient if it was a positive response, and increased by one dose gradient if it was a negative response. The observation was ended when the next patient with the 7th positive-negative response was reached. The ED50 of each group was calculated using the probit model.
Measured: three weeks
Isoradiation pattern
The ED50 determined for groups A and B was plotted on the isoradiogram. The ED50 of etomidate and its 95% confidence interval were plotted on the horizontal axis, and the ED50 of remimazolam and its 95% confidence interval were plotted on the vertical axis. The two ED50 were connected to form an additive line, and the confidence interval was connected to form an additive line with 95% confidence interval. When the two drugs were used together, the effect intensity of the compound drugs fell on the additive line (or within the confidence interval), indicating that the two drugs had additive effect. On the left side of the addition line and confidence interval, it indicated that the two drugs had synergistic effect. If it falls on the right side, it is antagonistic.
Measured: 24 hours
drug correlation coefficient
The drug correlation coefficient = 1/(actual dose of remimazolam/ED50 of remimazolam + actual dose of etomidate/ED50 of etomidate).
Measured: 24 hours
Secondary outcomes (3)
muscle tremor
Side effects of etomidate
Measured: 5 weeks
Bradycardia
The heart rate was less than 45 beats per minute
Measured: 5 weeks
hypotension
Blood pressure is lower than the baseline by 20%.
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2025
- Study start12 Jun 2025 (estimated)
- Primary completion19 Jun 2025 (estimated)
- Study completion19 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Induction AnesthesiaStudies 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Hospital of Shanxi Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zheng Guo, Second Hospital of Shanxi Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07012902
- Sponsor's protocol ID
- yuewei20250519
- Status last verified
- Jun 2025
- First submitted
- 19 May 2025
- Last updated
- 10 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Interaction Between Remimazolam and Etomidate During Induction of General Anesthesia Was Studied by Isoradiometric Analysis
- ClinicalTrials.gov ID
- NCT07012902
- Acronym / sponsor ID
- yuewei20250519
- Conditions
- Induction Anesthesia, Drug Interactions
- Keywords
- Isoradiation analysis, etomidate, remimazolam
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- Second Hospital of Shanxi Medical UniversityUniversity, hospital or other
- Study start
- 12 Jun 2025 (estimated)
- Primary completion
- 19 Jun 2025 (estimated)
- Study completion
- 19 Jul 2025 (estimated)
- First posted
- 10 Jun 2025 (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.
In modern anesthesia practice, anesthesiologists often need to choose a combination of multiple drugs according to the specific conditions and surgical needs of patients, which can not only achieve more fine anesthesia management, but also improve perioperative safety and patient comfort. In clinical practice, anesthesiologists will use etomidate combined with a small dose of remimazolam for anesthesia induction to obtain more stable hemodynamics, prevent intraoperative awareness, and relieve anxiety.However, what is the best dose ratio of etomidate combined with remimazolam, the current literature does not give clear indicators.
Detailed description
The experiment was divided into two steps. Step 1: Patients were randomly divided into group A (remimazolam induction group) and group B (etomidate induction group) according to the random number table, and group A was selected according to the literature. In group B, the initial dose was 0.2mg/kg, and 0.120mg/kg, and the ratio of successive doses was 1:0.8 and 1: 0.6, the ED50 of group A and group B was calculated by the sequential method, and the calculated remimazolam and etomidate were used as the initial doses of subgroups Step 2: According to the random number table, the patients were divided into group C (0.25ED50 remimazolam +0.75ED50 etomidate), group D (0.5ED50 remimazolam +0.50ED50 etomidate), group E (0.75ED50 remimazolam +0.25ED50 etomidate), and the dose of remimazolam in each group was fixed. The ED50 of etomidate in group C, group D and group E were calculated by sequential method.
Anesthesia methods: One hundred and twenty-five patients of both sexes, aged 18-60 yr, of American Society of Anesthesiologists physical status I-II, BIM: 18-30kg/m2, undergoing general anesthesia in the Second Hospital of Shanxi Medical University, were selected. Before operation, the patients were required to fast and drink, and had not received special preoperative medication. After the patient entered the room, blood pressure, heart rate, oxygen saturation and BIS were monitored and oxygen inhalation was given to the mask for 5L/min. After the tripartite verification was correct, intravenous access was established in the patient's upper limb, fluid infusion was opened, anesthesia was induced, remimazolam and etomidate were injected directly and slowly intravenously, and remimazolam and etomidate were injected for more than 10s according to the dosage of each group. Two drugs were injected at an interval of 10s or more. After the completion of one drug injection, 5ml normal saline was used to flush the tube, and the score was scored 2 minutes after intravenous injection. BIS value of 45-60 was considered as a positive response, and the dose gradient of the next patient was reduced. The observation was calculated as the first patient with positive to negative turning point, and the observation ended when the next patient with positive to negative reaction at the seventh turning point. The secondary outcome measures were the incidence of adverse reactions, changes in heart rate and blood pressure. At the end of the observation, if the patient showed a negative reaction, 0.08mg/kg etomidate was added for sedation, and then sufentanil and rocuronium were given for tracheal intubation in turn, and then surgery was performed.The demographic data of the patients were collected, including: gender, age, height, weight, BIM Statistical methods: probit model was used to calculate ED50 of each group, and the drug correlation coefficient was introduced as 1/(actual dose of remimazolam/ED50 of remimazolam + actual dose of etomidate/ED50 of etomidate). The measurement data with normal distribution were expressed as mean ± standard deviation (x±s). The measurement data with normal distribution between group A and group B were compared by two independent sample t test, and the comparison between group C, group D and group E was compared by one-way analysis of variance. Graphpad prism software was used to make five groups of sequential experimental plots and iso-radiation analysis plots when P<0.05 was considered statistically significant.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group A (remimazolam induction group) | Experimental | Drug: EtomidateThe ED50 of group A was calculated by sequential method |
| Group B (etomidate induction group) | Experimental | Drug: RemimazolamThe ED50 of group B was calculated by sequential method |
| group C (0.25ED50 remimazolam +0.75ED50 etomidate) | Experimental | Drug: Remimazolam-etomidateThe ED50 of etomidate in group C were calculated by sequential method. |
| Group D (0.5ED50 remimazolam +0.5ED50 etomidate) | Experimental | Drug: Remimazolam-etomidateThe ED50 of etomidate in group Dwere calculated by sequential method. |
| Group E (0.75ED50 remimazolam +0.25 etomidate) | Experimental | Drug: Remimazolam-etomidateThe ED50 of etomidate in group E were calculated by sequential method. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Both sexes
- aged 18-60 yr
- ASA physical status I-II
- BIM: 18-28kg/m²
Key exclusion criteria (5 listed)
- allergic to remimazolam and etomidate
- in pregnancy or lactation
- serious cardiovascular diseases, long-term alcoholism
- used sedative drugs or opioids within 24 hours
- severe mental illness and myasthenia gravis -
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 |
|---|---|---|
| EtomidateGroup A was induced with etomidate, the initial dose was 0.120mg/kg, and the ratio of adjacent doses was 1:0.6 | Drug | Group A (remimazolam induction group) |
| RemimazolamGroup B was induced with remimazolam, the initial dose was 0.20mg/kg, and the ratio of adjacent doses was 1:0.8 | Drug | Group B (etomidate induction group) |
| Remimazolam-etomidateIn group C, 0.25ED50 remimazolam +0.75ED50 etomidate was used as the initial measurement In group D, 0.5ED50 remimazolam +0.5ED50 etomidate was used as the initial measurement In group E, 0.75ED50 of remimazolam +0.25ED50 of etomidate was used as the initial measurement | Drug | Group D (0.5ED50 remimazolam +0.5ED50 etomidate), Group E (0.75ED50 remimazolam +0.25 etomidate), group C (0.25ED50 remimazolam +0.75ED50 etomidate) |
Primary outcome
The ED50 value of etomidate in Group A
Time frame: one week
The sequential method was used to calculate the median effective dose of etomidate in group A. When the patient's BIS value was between 45 and 60, it was considered a positive response. For the next patient, the dose was reduced by one dose gradient; conversely, if it was a negative response, the dose was increased by one dose gradient. The observation was stopped when the first patient reached the positive-negative turning point, and the next patient with the positive-negative reaction was reached for the seventh turning point. The ED50 of each group was calculated using the probit model.
The ED50 value of Remimazolam in Group B
Time frame: one week
The sequential method was used to calculate the median effective dose of remimazolam in group B. A positive reaction was defined as a patient's BIS value ranging from 45 to 60. For the next patient, the dose was reduced by one dose gradient if it was a positive reaction, and increased by one dose gradient if it was a negative reaction. The observation was stopped when the next patient with the 7th positive-negative reaction point was reached. The ED50 of each group was calculated using the probit model.
Group C D E: etomidate ED50
Time frame: three weeks
The sequential method was adopted to calculate the median effective dose of etomidate for groups C, D, and E separately. A patient was considered to have a positive response if their BIS value was between 45 and 60. For the next patient, the dose was reduced by one dose gradient if it was a positive response, and increased by one dose gradient if it was a negative response. The observation was ended when the next patient with the 7th positive-negative response was reached. The ED50 of each group was calculated using the probit model.
Isoradiation pattern
Time frame: 24 hours
The ED50 determined for groups A and B was plotted on the isoradiogram. The ED50 of etomidate and its 95% confidence interval were plotted on the horizontal axis, and the ED50 of remimazolam and its 95% confidence interval were plotted on the vertical axis. The two ED50 were connected to form an additive line, and the confidence interval was connected to form an additive line with 95% confidence interval. When the two drugs were used together, the effect intensity of the compound drugs fell on the additive line (or within the confidence interval), indicating that the two drugs had additive effect. On the left side of the addition line and confidence interval, it indicated that the two drugs had synergistic effect. If it falls on the right side, it is antagonistic.
drug correlation coefficient
Time frame: 24 hours
The drug correlation coefficient = 1/(actual dose of remimazolam/ED50 of remimazolam + actual dose of etomidate/ED50 of etomidate).
3 secondary outcomes
muscle tremor
Time frame: 5 weeks
Bradycardia
Time frame: 5 weeks
hypotension
Time frame: 5 weeks
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 10 Jun 2025.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Etomidate, Remimazolam and Remimazolam-etomidate in people with Induction Anesthesia and Drug Interactions, run by Second Hospital of Shanxi Medical University at 1 site in China.
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 5 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: opening soon, as of the sponsor's last update on 10 Jun 2025. 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 China. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The ED50 value of etomidate in Group A (time frame: one week). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jun 2025.