Flumazenil to Antagonize RemimazolamPhase 1NCT06531369
Flumazenil Antagonism of Remimazolam in Kidney Transplant Patients
A Phase 1 study testing Flumazenil Injection（F1 group）, Flumazenil Injection（F2 group） and Saline（C group） in people with Flumazenil to Antagonize Remimazolam and Remimazolam, run by Qianfoshan Hospital.
Trial summary
To investigate the effect of different doses of flumazenil antagonism on remimazolam plasma concentration in patients undergoing renal transplantation under general anesthesia. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Flumazenil to Antagonize Remimazolam, Remimazolam, Renal Transplantation
- What is being tested?
- Flumazenil Injection（F1 group）, Flumazenil Injection（F2 group） and Saline（C group）
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Jul 2024to Mar 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years and < 65 years
- Patients undergoing elective kidney transplant surgery
- Signed the informed consent for the clinical study
Who cannot join
- Liver decompensation (Child B/C)
- History of liver transplant
- Previous allergies or other serious adverse reactions to narcotic drugs
- Intraoperative depth monitoring of anesthesia is not expected
- Preoperative ASA rating of 5
- Received general anesthesia in the 30 days prior to surgery or plan to receive it again within 30 days
- Plan to extend airway protection or mechanical ventilation support time after surgery
- Previous participation in this study
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Application of Flumazenil to Antagonize Remimazolam and Evaluation of Remimazolam Plasma Concentration in Kidney Transplant Patients: A Randomized Controlled Trial
To investigate the effect of different doses of flumazenil antagonism on remimazolam plasma concentration in patients undergoing renal transplantation under general anesthesia.
Read the detailed description
During the surgery, other anesthetics, intraoperative monitoring, fluid management, and postoperative pain management were implemented according to a unified standard.
- Intraoperative Monitoring All study participants underwent the following routine intraoperative monitoring: blood pressure, electrocardiogram, pulse oximetry, end-tidal CO2 pressure, body temperature, and depth of anesthesia monitoring. Additional monitoring such as central venous pressure, invasive continuous arterial blood pressure, and cardiac output was selected based on clinical needs and the attending anesthesiologist's judgment.
- Anesthetic Regimen All study participants underwent general anesthesia with endotracheal intubation and received total intravenous anesthesia with remimazolam. For anesthesia induction, it was recommended to administer remimazolam at a rate of 6-12 mg/kg/h until loss of consciousness; for maintenance, it was recommended to administer at a rate of 0.5-2.0 mg/kg/h. At the end of anesthesia: C Group: Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. R1 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. R2 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later. None of the three groups used inhalation anesthetics such as sevoflurane, or other intravenous sedatives such as midazolam, dexmedetomidine, or etomidate. Intraoperative analgesics were administered with remifentanil via continuous intravenous infusion. Muscle relaxants included cisatracurium, with a single intravenous injection of cisatracurium 0.2 mg/kg for induction to meet muscle relaxation conditions for tracheal intubation, and intermittent single intravenous bolus of cisatracurium 0.05 mg/kg to maintain muscle relaxation as needed for the surgery.
- Depth of Anesthesia Management Narcotrend was measured as a baseline value within 60 minutes before administration, and intraoperative depth of anesthesia monitoring was conducted using Narcotrend. The dose of remimazolam was adjusted according to hemodynamics to ensure that the patient's anesthesia depth (Narcotrend Index, NCI) was maintained between 27 and 60. (If the NCI value could not be maintained at ≤ 60 or there were signs of potential inadequate anesthesia (e.g., coughing, sweating, and patient movement), and the maximum bolus and infusion doses of remimazolam had been administered, rescue medications such as midazolam or propofol were allowed.)
- Blood Pressure Management Intraoperative blood pressure control aimed to maintain a mean arterial pressure (MAP) of no less than 65 mmHg, which was the minimum blood pressure tolerated by the anesthesiologist during surgery, not the target value. Higher or lower intraoperative blood pressure management targets could be adopted based on the participant's condition and/or the surgeon's requirements. The use of vasoactive drugs was minimized. If vasoactive drugs were needed, ephedrine 5 mg (maximum dose not exceeding 30 mg) and norepinephrine 10 µg intravenous bolus or continuous infusion were used. Norepinephrine was prepared and used as follows: 2 mg of norepinephrine bitartrate was diluted in 100 mL of saline to a concentration of 20 µg/mL, with an initial dose of 0.01 µg/kg/min. The dose was adjusted in real-time based on intraoperative blood pressure, using the minimum amount of drug necessary to maintain the target MAP. In case of severe bradycardia (<40 beats/min), the norepinephrine infusion rate could be reduced, and an appropriate dose of atropine could be administered intravenously based on the anesthesiologist's judgment.
- Respiratory Management A lung-protective ventilation strategy was recommended during surgery: setting a tidal volume of 6-8 mL/kg, an inspiratory-expiratory ratio of 1:2, and adjusting positive end-expiratory pressure (PEEP) to 5-10 cmH2O, maintaining end-tidal CO2 pressure between 35-45 mmHg, and using periodic lung recruitment maneuvers. Spontaneous breathing was restored as soon as possible at the end of surgery, and the endotracheal tube was removed.
- Fluid Management Crystalloids were the primary fluids recommended during surgery, following a moderately liberal fluid management strategy.
- Other Management Points Comprehensive warming measures were recommended during surgery to maintain core temperature at 37°C. Blood transfusions were recommended based on bleeding and arterial blood gas analysis to maintain hemoglobin levels at ≥70 g/L. Postoperative pain management was selected based on the participant's preoperative preferences and the anesthesiologist's judgment to provide the best pain relief for the participant.
- Postoperative Management C Group: Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later.
R1 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later.
R2 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later.
Arterial blood samples of 3 mL were collected in plastic tubes containing EDTA K3 (Becton Dickinson, Germany) at T1 (end of surgery), T2 (25 minutes after the end of surgery), and T3 (50 minutes after the end of surgery). The arterial catheter was flushed with 2 mL of saline after each sample collection. Samples were kept on ice water and centrifuged at approximately 2000 rpm at 4°C for 10 minutes within 40 minutes of collection. Plasma was separated into polypropylene tubes (Nunc cryogenic vial cryo tubes, Thermo Fisher Scientific, USA) within 15 minutes and stored at -70°C. The sample collection time was recorded. The samples were sent to a third-party testing company for analysis within two months of collection.
Data recorded included the time to eye-opening, extubation time, the amount of remimazolam used, intraoperative analgesic use, hemodynamic parameters at T0 (admission), T1, T2, and T3, MMSE scores 24h and 72h before and after surgery, Narcotrend values at T0, T1, T2, and T3, PACU stay time, and the incidence of nausea and vomiting during PACU stay; postoperative complications such as atelectasis, cardiovascular and cerebrovascular events (stroke, myocardial infarction), all-cause mortality within 30 days postoperatively, total length of hospital stay (days) for survivors within 30 days postoperatively, and unplanned readmissions within 30 days postoperatively.
- Being tested
- Flumazenil Injection（F1 group）, Flumazenil Injection（F2 group）, Saline（C group）
- Keywords
- Flumazenil, Remimazolam, renal transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flumazenil Injection（F1 group）Drug
Also called Flumazenil at Different Dosages
Flumazenil Injection（F1 group）: Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later.
Flumazenil Injection（F2 group）Drug
Also called Flumazenil at Different Dosages
Flumazenil Injection（F2 group）: Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later.
Saline（C group）Drug
Also called control group
Flumazenil Injection（F2 group）: Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later.
| Study group | Role | What they receive |
|---|---|---|
| "Flumazenil group 1（F1 group）"+"Flumazenil group 2（F2 group）" | Active comparator | "Flumazenil group 1（F1）":Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later.
"Flumazenil group 2（F2）":Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later. Receives: Drug: Flumazenil Injection（F1 group）; Drug: Flumazenil Injection（F2 group） |
| Control Group (C group) | Placebo comparator | Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. Receives: Drug: Saline（C group） |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Concentration of Remimazolam
3ml arterial blood was drawn to determine the blood concentration of remimazolam
Measured: T1 (immediately at the end of surgery)
Plasma Concentration of Remimazolam
3ml arterial blood was drawn to determine the blood concentration of remimazolam
Measured: T2 (25 minutes after the end of surgery)
Plasma Concentration of Remimazolam
3ml arterial blood was drawn to determine the blood concentration of remimazolam
Measured: T3 (50 minutes after the end of surgery)
Secondary outcomes (33)
Record eye opening time and extubation time
Record eye opening time and extubation time
Measured: after surgery,an average of 30 minutes
remimazolam usage
remimazolam usage
Measured: immediately at the end of surgery
The amount of analgesic drugs used during operation
The amount of analgesic drugs used during operation
Measured: 3 days after surgery
Heart Rate (HR)
Unit: beats per minute (bpm) Measurement of heart rate upon entering the operating room, before anesthesia administration, to monitor baseline cardiac activity.
Measured: T0（Entering the Operating Room, Before Anesthesia）
Blood Pressure (BP)
Unit: millimeters of mercury (mmHg) Measurement of systolic and diastolic blood pressure upon entering the operating room, before anesthesia administration, to monitor baseline blood pressure.
Measured: T0（Entering the Operating Room, Before Anesthesia）
Mean Arterial Pressure (MAP)
Unit: millimeters of mercury (mmHg) Calculation of mean arterial pressure using the formula: (Systolic BP + 2*Diastolic BP) / 3, upon entering the operating room, before anesthesia administration, to monitor baseline arterial pressure.
Measured: T0（Entering the Operating Room, Before Anesthesia）
Oxygen Saturation (SpO2)
Unit: percentage (%) Measurement of blood oxygen saturation upon entering the operating room, before anesthesia administration, to ensure baseline oxygenation levels.
Measured: T0（Entering the Operating Room, Before Anesthesia）
Heart Rate (HR)
Unit: beats per minute (bpm) Measurement of heart rate upon entering the operating room, before anesthesia administration, to monitor baseline cardiac activity.
Measured: T1(immediately at the end of surgery)
Blood Pressure (BP)
Unit: millimeters of mercury (mmHg) Measurement of systolic and diastolic blood pressure upon entering the operating room, before anesthesia administration, to monitor baseline blood pressure.
Measured: T1(immediately at the end of surgery)
Mean Arterial Pressure (MAP)
Unit: millimeters of mercury (mmHg) Calculation of mean arterial pressure using the formula: (Systolic BP + 2*Diastolic BP) / 3, upon entering the operating room, before anesthesia administration, to monitor baseline arterial pressure.
Measured: T1(immediately at the end of surgery)
Oxygen Saturation (SpO2)
Unit: percentage (%) Measurement of blood oxygen saturation upon entering the operating room, before anesthesia administration, to ensure baseline oxygenation levels.
Measured: T1(immediately at the end of surgery)
Heart Rate (HR)
Unit: beats per minute (bpm) Measurement of heart rate upon entering the operating room, before anesthesia administration, to monitor baseline cardiac activity.
Measured: T2（25 minutes after the end of surgery)
Blood Pressure (BP)
Unit: millimeters of mercury (mmHg) Measurement of systolic and diastolic blood pressure upon entering the operating room, before anesthesia administration, to monitor baseline blood pressure.
Measured: T2（25 minutes after the end of surgery)
Mean Arterial Pressure (MAP)
Unit: millimeters of mercury (mmHg) Calculation of mean arterial pressure using the formula: (Systolic BP + 2*Diastolic BP) / 3, upon entering the operating room, before anesthesia administration, to monitor baseline arterial pressure.
Measured: T2（25 minutes after the end of surgery)
Oxygen Saturation (SpO2)
Unit: percentage (%) Measurement of blood oxygen saturation upon entering the operating room, before anesthesia administration, to ensure baseline oxygenation levels.
Measured: T2（25 minutes after the end of surgery)
Heart Rate (HR)
Unit: beats per minute (bpm) Measurement of heart rate upon entering the operating room, before anesthesia administration, to monitor baseline cardiac activity.
Measured: T3（50 minutes after the end of surgery)
Blood Pressure (BP)
Unit: millimeters of mercury (mmHg) Measurement of systolic and diastolic blood pressure upon entering the operating room, before anesthesia administration, to monitor baseline blood pressure.
Measured: T3（50 minutes after the end of surgery)
Mean Arterial Pressure (MAP)
Unit: millimeters of mercury (mmHg) Calculation of mean arterial pressure using the formula: (Systolic BP + 2*Diastolic BP) / 3, upon entering the operating room, before anesthesia administration, to monitor baseline arterial pressure.
Measured: T3（50 minutes after the end of surgery)
Oxygen Saturation (SpO2)
Unit: percentage (%) Measurement of blood oxygen saturation upon entering the operating room, before anesthesia administration, to ensure baseline oxygenation levels.
Measured: T3（50 minutes after the end of surgery)
Mini-Mental State Examination （MMSE )scores were obtained before, 24h and 72h after surgery
Scale Description: The MMSE is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language, and visual-spatial skills.
Unit: Score (0-30) Score Range: The MMSE score ranges from 0 to 30.
Interpretation of Scores:
Higher Scores: Indicate better cognitive function. Lower Scores: Indicate worse cognitive function.
Score Interpretation:
Cognitive Impairment:
The maximum score is 30 points. A score of 27-30 points is considered normal, while a score of <27 points indicates cognitive impairment.
Dementia Classification Criteria:
Illiterate: ≤17 points Primary School Level: ≤20 points Secondary School Level (including technical secondary school): ≤22 points University Level (including junior college): ≤23 points
Dementia Severity Grading:
Mild: MMSE ≥21 points Moderate: MMSE 10-20 points Severe: MMSE ≤9 points
Data Collection Points:
Before Surgery (Entering the Operating Room, Before Anesthesia)
Measured: Entering the Operating Room, Before Anesthesia
Mini-Mental State Examination （MMSE ）scores
Scale Description: The MMSE is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language, and visual-spatial skills.
Unit: Score (0-30) Score Range: The MMSE score ranges from 0 to 30.
Interpretation of Scores:
Higher Scores: Indicate better cognitive function. Lower Scores: Indicate worse cognitive function.
Score Interpretation:
Cognitive Impairment:
The maximum score is 30 points. A score of 27-30 points is considered normal, while a score of <27 points indicates cognitive impairment.
Dementia Classification Criteria:
Illiterate: ≤17 points Primary School Level: ≤20 points Secondary School Level (including technical secondary school): ≤22 points University Level (including junior college): ≤23 points
Dementia Severity Grading:
Mild: MMSE ≥21 points Moderate: MMSE 10-20 points Severe: MMSE ≤9 points
Data Collection Points:
24 Hours After Surgery
Measured: 24h after the end of surgery
Mini-Mental State Examination （MMSE ）scores
Scale Description: The MMSE is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language, and visual-spatial skills.
Unit: Score (0-30) Score Range: The MMSE score ranges from 0 to 30.
Interpretation of Scores:
Higher Scores: Indicate better cognitive function. Lower Scores: Indicate worse cognitive function.
Score Interpretation:
Cognitive Impairment:
The maximum score is 30 points. A score of 27-30 points is considered normal, while a score of <27 points indicates cognitive impairment.
Dementia Classification Criteria:
Illiterate: ≤17 points Primary School Level: ≤20 points Secondary School Level (including technical secondary school): ≤22 points University Level (including junior college): ≤23 points
Dementia Severity Grading:
Mild: MMSE ≥21 points Moderate: MMSE 10-20 points Severe: MMSE ≤9 points
Data Collection Points:
72 Hours After Surgery
Measured: 72 h after the end of surgery
Bispectral Index (BIS)
This outcome measure will record and report the Bispectral Index (BIS) values. The BIS values are quantitative electroencephalographic (EEG) parameters used to assess the depth of anesthesia and sedation levels.
Bispectral Index (BIS): A value ranging from 0 to 100, where lower values indicate deeper anesthesia and higher values indicate lighter sedation or wakefulness.
Measured: T0（Entering the Operating Room, Before Anesthesia）
Bispectral Index (BIS)
This outcome measure will record and report the Bispectral Index (BIS) values. The BIS values are quantitative electroencephalographic (EEG) parameters used to assess the depth of anesthesia and sedation levels.
Bispectral Index (BIS): A value ranging from 0 to 100, where lower values indicate deeper anesthesia and higher values indicate lighter sedation or wakefulness.
Measured: T1(immediately at the end of surgery)
Bispectral Index (BIS)
This outcome measure will record and report the Bispectral Index (BIS) values. The BIS values are quantitative electroencephalographic (EEG) parameters used to assess the depth of anesthesia and sedation levels.
Bispectral Index (BIS): A value ranging from 0 to 100, where lower values indicate deeper anesthesia and higher values indicate lighter sedation or wakefulness.
Measured: T2（25 minutes after the end of surgery)
Bispectral Index (BIS)
This outcome measure will record and report the Bispectral Index (BIS) values. The BIS values are quantitative electroencephalographic (EEG) parameters used to assess the depth of anesthesia and sedation levels.
Bispectral Index (BIS): A value ranging from 0 to 100, where lower values indicate deeper anesthesia and higher values indicate lighter sedation or wakefulness.
Measured: T3 (50 minutes after the end of surgery)
Duration of Post-Anesthesia Care Unit (PACU) Stay
Unit: Hours The total time spent in the Post-Anesthesia Care Unit (PACU) from the end of surgery until discharge to the ward.
Measured: Before Leaving PACU Post-Surgery
Occurrence of nausea
Unit: Incidence (Yes/No) The occurrence of nausea during the stay in the PACU, recorded as a binary outcome (Yes or No).
Measured: 3 days after surgery
Occurrence of vomiting
Unit: Incidence (Yes/No) The occurrence of vomiting during the stay in the PACU, recorded as a binary outcome (Yes or No).
Measured: 3 days after surgery
Number of Participants with Postoperative Pulmonary Atelectasis, Cardiovascular and Cerebrovascular Adverse Events
This measure will report the number of participants who experience postoperative pulmonary atelectasis and adverse cardiovascular and cerebrovascular events, including cerebral infarction, cerebral hemorrhage, and heart infarction, within 30 days after surgery.
Measured: 30 days after surgery
All-cause death within 30 days after surgery
All-cause death within 30 days after surgery
Measured: 30 days after surgery
Total hospital stay for survivors 30 days after surgery
Total hospital stay for survivors 30 days after surgery
Measured: 30 days after surgery
Unplanned second hospital admission within 30 days after surgery
Unplanned second hospital admission within 30 days after surgery
Measured: 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2024
- Study startJul 2024 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Flumazenil to Antagonize RemimazolamStudies of the same condition, open and under way.
- More trials run by Qianfoshan HospitalThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qianfoshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianbo Wu, Qianfoshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06531369
- Sponsor's protocol ID
- YXLL-KY-2024(059)
- Status last verified
- Jul 2024
- First submitted
- 22 Jun 2024
- Last updated
- 1 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Flumazenil to Antagonize Remimazolam and Evaluation of Remimazolam Plasma Concentration in Kidney Transplant Patients: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06531369
- Acronym / sponsor ID
- YXLL-KY-2024(059)
- Keywords
- Flumazenil, Remimazolam, renal transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Qianfoshan HospitalUniversity, hospital or other
- Study start
- Jul 2024 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 1 Aug 2024 (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.
To investigate the effect of different doses of flumazenil antagonism on remimazolam plasma concentration in patients undergoing renal transplantation under general anesthesia.
Detailed description
During the surgery, other anesthetics, intraoperative monitoring, fluid management, and postoperative pain management were implemented according to a unified standard.
- Intraoperative Monitoring All study participants underwent the following routine intraoperative monitoring: blood pressure, electrocardiogram, pulse oximetry, end-tidal CO2 pressure, body temperature, and depth of anesthesia monitoring. Additional monitoring such as central venous pressure, invasive continuous arterial blood pressure, and cardiac output was selected based on clinical needs and the attending anesthesiologist's judgment.
- Anesthetic Regimen All study participants underwent general anesthesia with endotracheal intubation and received total intravenous anesthesia with remimazolam. For anesthesia induction, it was recommended to administer remimazolam at a rate of 6-12 mg/kg/h until loss of consciousness; for maintenance, it was recommended to administer at a rate of 0.5-2.0 mg/kg/h. At the end of anesthesia: C Group: Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. R1 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. R2 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later. None of the three groups used inhalation anesthetics such as sevoflurane, or other intravenous sedatives such as midazolam, dexmedetomidine, or etomidate. Intraoperative analgesics were administered with remifentanil via continuous intravenous infusion. Muscle relaxants included cisatracurium, with a single intravenous injection of cisatracurium 0.2 mg/kg for induction to meet muscle relaxation conditions for tracheal intubation, and intermittent single intravenous bolus of cisatracurium 0.05 mg/kg to maintain muscle relaxation as needed for the surgery.
- Depth of Anesthesia Management Narcotrend was measured as a baseline value within 60 minutes before administration, and intraoperative depth of anesthesia monitoring was conducted using Narcotrend. The dose of remimazolam was adjusted according to hemodynamics to ensure that the patient's anesthesia depth (Narcotrend Index, NCI) was maintained between 27 and 60. (If the NCI value could not be maintained at ≤ 60 or there were signs of potential inadequate anesthesia (e.g., coughing, sweating, and patient movement), and the maximum bolus and infusion doses of remimazolam had been administered, rescue medications such as midazolam or propofol were allowed.)
- Blood Pressure Management Intraoperative blood pressure control aimed to maintain a mean arterial pressure (MAP) of no less than 65 mmHg, which was the minimum blood pressure tolerated by the anesthesiologist during surgery, not the target value. Higher or lower intraoperative blood pressure management targets could be adopted based on the participant's condition and/or the surgeon's requirements. The use of vasoactive drugs was minimized. If vasoactive drugs were needed, ephedrine 5 mg (maximum dose not exceeding 30 mg) and norepinephrine 10 µg intravenous bolus or continuous infusion were used. Norepinephrine was prepared and used as follows: 2 mg of norepinephrine bitartrate was diluted in 100 mL of saline to a concentration of 20 µg/mL, with an initial dose of 0.01 µg/kg/min. The dose was adjusted in real-time based on intraoperative blood pressure, using the minimum amount of drug necessary to maintain the target MAP. In case of severe bradycardia (<40 beats/min), the norepinephrine infusion rate could be reduced, and an appropriate dose of atropine could be administered intravenously based on the anesthesiologist's judgment.
- Respiratory Management A lung-protective ventilation strategy was recommended during surgery: setting a tidal volume of 6-8 mL/kg, an inspiratory-expiratory ratio of 1:2, and adjusting positive end-expiratory pressure (PEEP) to 5-10 cmH2O, maintaining end-tidal CO2 pressure between 35-45 mmHg, and using periodic lung recruitment maneuvers. Spontaneous breathing was restored as soon as possible at the end of surgery, and the endotracheal tube was removed.
- Fluid Management Crystalloids were the primary fluids recommended during surgery, following a moderately liberal fluid management strategy.
- Other Management Points Comprehensive warming measures were recommended during surgery to maintain core temperature at 37°C. Blood transfusions were recommended based on bleeding and arterial blood gas analysis to maintain hemoglobin levels at ≥70 g/L. Postoperative pain management was selected based on the participant's preoperative preferences and the anesthesiologist's judgment to provide the best pain relief for the participant.
- Postoperative Management C Group: Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later.
R1 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later.
R2 Group: Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later.
Arterial blood samples of 3 mL were collected in plastic tubes containing EDTA K3 (Becton Dickinson, Germany) at T1 (end of surgery), T2 (25 minutes after the end of surgery), and T3 (50 minutes after the end of surgery). The arterial catheter was flushed with 2 mL of saline after each sample collection. Samples were kept on ice water and centrifuged at approximately 2000 rpm at 4°C for 10 minutes within 40 minutes of collection. Plasma was separated into polypropylene tubes (Nunc cryogenic vial cryo tubes, Thermo Fisher Scientific, USA) within 15 minutes and stored at -70°C. The sample collection time was recorded. The samples were sent to a third-party testing company for analysis within two months of collection.
Data recorded included the time to eye-opening, extubation time, the amount of remimazolam used, intraoperative analgesic use, hemodynamic parameters at T0 (admission), T1, T2, and T3, MMSE scores 24h and 72h before and after surgery, Narcotrend values at T0, T1, T2, and T3, PACU stay time, and the incidence of nausea and vomiting during PACU stay; postoperative complications such as atelectasis, cardiovascular and cerebrovascular events (stroke, myocardial infarction), all-cause mortality within 30 days postoperatively, total length of hospital stay (days) for survivors within 30 days postoperatively, and unplanned readmissions within 30 days postoperatively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| "Flumazenil group 1（F1 group）"+"Flumazenil group 2（F2 group）" | Active comparator | Drug: Flumazenil Injection（F1 group）, Drug: Flumazenil Injection（F2 group）"Flumazenil group 1（F1）":Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. "Flumazenil group 2（F2）":Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later. |
| Control Group (C group) | Placebo comparator | Drug: Saline（C group）Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 18 years and < 65 years
- Patients undergoing elective kidney transplant surgery
- Signed the informed consent for the clinical study
Key exclusion criteria (8 listed)
- Liver decompensation (Child B/C)
- History of liver transplant
- Previous allergies or other serious adverse reactions to narcotic drugs
- Intraoperative depth monitoring of anesthesia is not expected
- Preoperative ASA rating of 5
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 |
|---|---|---|
| Flumazenil Injection（F1 group）Also: Flumazenil at Different DosagesFlumazenil Injection（F1 group）: Immediately after surgery, 0.5 mg flumazenil was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. | Drug | "Flumazenil group 1（F1 group）"+"Flumazenil group 2（F2 group）" |
| Flumazenil Injection（F2 group）Also: Flumazenil at Different DosagesFlumazenil Injection（F2 group）: Immediately after surgery, 0.5 mg flumazenil was administered, followed by 0.3 mg flumazenil 25 minutes later. | Drug | "Flumazenil group 1（F1 group）"+"Flumazenil group 2（F2 group）" |
| Saline（C group）Also: control groupFlumazenil Injection（F2 group）: Immediately after surgery, an equal volume of saline (equal to the volume of 0.5 mg flumazenil) was administered, followed by an equal volume of saline (equal to the volume of 0.3 mg flumazenil) 25 minutes later. | Drug | Control Group (C group) |
Primary outcome
Plasma Concentration of Remimazolam
Time frame: T1 (immediately at the end of surgery)
3ml arterial blood was drawn to determine the blood concentration of remimazolam
Plasma Concentration of Remimazolam
Time frame: T2 (25 minutes after the end of surgery)
3ml arterial blood was drawn to determine the blood concentration of remimazolam
Plasma Concentration of Remimazolam
Time frame: T3 (50 minutes after the end of surgery)
3ml arterial blood was drawn to determine the blood concentration of remimazolam
33 secondary outcomes
Record eye opening time and extubation time
Time frame: after surgery,an average of 30 minutes
remimazolam usage
Time frame: immediately at the end of surgery
The amount of analgesic drugs used during operation
Time frame: 3 days after surgery
Heart Rate (HR)
Time frame: T0（Entering the Operating Room, Before Anesthesia）
Blood Pressure (BP)
Time frame: T0（Entering the Operating Room, Before Anesthesia）
Mean Arterial Pressure (MAP)
Time frame: T0（Entering the Operating Room, Before Anesthesia）
Oxygen Saturation (SpO2)
Time frame: T0（Entering the Operating Room, Before Anesthesia）
Heart Rate (HR)
Time frame: T1(immediately at the end of surgery)
Blood Pressure (BP)
Time frame: T1(immediately at the end of surgery)
Mean Arterial Pressure (MAP)
Time frame: T1(immediately at the end of surgery)
Oxygen Saturation (SpO2)
Time frame: T1(immediately at the end of surgery)
Heart Rate (HR)
Time frame: T2（25 minutes after the end of surgery)
Blood Pressure (BP)
Time frame: T2（25 minutes after the end of surgery)
Mean Arterial Pressure (MAP)
Time frame: T2（25 minutes after the end of surgery)
Oxygen Saturation (SpO2)
Time frame: T2（25 minutes after the end of surgery)
Heart Rate (HR)
Time frame: T3（50 minutes after the end of surgery)
Blood Pressure (BP)
Time frame: T3（50 minutes after the end of surgery)
Mean Arterial Pressure (MAP)
Time frame: T3（50 minutes after the end of surgery)
Oxygen Saturation (SpO2)
Time frame: T3（50 minutes after the end of surgery)
Mini-Mental State Examination （MMSE )scores were obtained before, 24h and 72h after surgery
Time frame: Entering the Operating Room, Before Anesthesia
Mini-Mental State Examination （MMSE ）scores
Time frame: 24h after the end of surgery
Mini-Mental State Examination （MMSE ）scores
Time frame: 72 h after the end of surgery
Bispectral Index (BIS)
Time frame: T0（Entering the Operating Room, Before Anesthesia）
Bispectral Index (BIS)
Time frame: T1(immediately at the end of surgery)
Bispectral Index (BIS)
Time frame: T2（25 minutes after the end of surgery)
Bispectral Index (BIS)
Time frame: T3 (50 minutes after the end of surgery)
Duration of Post-Anesthesia Care Unit (PACU) Stay
Time frame: Before Leaving PACU Post-Surgery
Occurrence of nausea
Time frame: 3 days after surgery
Occurrence of vomiting
Time frame: 3 days after surgery
Number of Participants with Postoperative Pulmonary Atelectasis, Cardiovascular and Cerebrovascular Adverse Events
Time frame: 30 days after surgery
All-cause death within 30 days after surgery
Time frame: 30 days after surgery
Total hospital stay for survivors 30 days after surgery
Time frame: 30 days after surgery
Unplanned second hospital admission within 30 days after surgery
Time frame: 30 days after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2024.
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. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Flumazenil Injection（F1 group）, Flumazenil Injection（F2 group） and Saline（C group） in people with Flumazenil to Antagonize Remimazolam and Remimazolam, run by Qianfoshan Hospital.
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 3 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 1 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guanghan Wu, Attending physician (18763995357, GuanghanWu2021@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Concentration of Remimazolam (time frame: T1 (immediately at the end of surgery)). The study lists 3 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 1 Aug 2024.