[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659360":3},{"organization":4,"outcomesModule":7,"designInfo":129,"detailedDescription":136,"studyPopulation":128,"armGroups":137,"interventions":144,"overallOfficials":128,"centralContacts":128,"locations":152,"responsibleParty":170,"collaborators":172,"id":178,"slug":179,"hasResults":180,"nctId":181,"briefTitle":182,"officialTitle":183,"acronym":128,"eligibilityCriteria":184,"healthyVolunteers":180,"sex":185,"minAge":186,"maxAge":128,"enrollmentInfo":187,"targetDuration":128,"studyType":190,"phases":191,"briefSummary":193,"conditions":194,"keywords":196,"overallStatus":202,"whyStopped":128,"lastUpdateSubmitDate":203,"lastUpdatePostDateStruct":204,"startDateStruct":207,"completionDateStruct":209,"leadSponsor":211,"locationsCount":212},{"fullName":5,"class":6},"Seoul National University Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":128},[9],{"measure":10,"description":11,"timeFrame":12},"Between-Patient Coefficient of Variation in Model-Predicted Effect-Site Concentration Associated With Target Sedation","Between-patient variability in the remimazolam effect-site concentration associated with target sedation (Modified Observer's Assessment of Alertness\u002FSedation \\[MOAA\u002FS\\] \\\u003C=3), expressed as a coefficient of variation (%). Eleveld model-predicted concentrations are reconstructed after surgery from dosing histories and patient covariates. The protocol specifies maintenance observations at MOAA\u002FS 3 and an ordinal mixed-effects concentration-response analysis to estimate variability at the MOAA\u002FS \\\u003C=3 threshold. MOAA\u002FS ranges from 0 (no response to painful stimulus) to 5 (readily responsive to a name spoken in a normal tone); lower scores indicate deeper sedation.","During intraoperative remimazolam sedation, from loading through infusion cessation on the day of surgery",[14,18,21,25,29,32,35,38,41,44,47,51,55,58,62,66,70,74,77,80,83,86,89,92,95,98,101,105,109,112,115,118,121,124],{"measure":15,"description":16,"timeFrame":17},"Ratio of Individual Representative Effect-Site Concentration to the Eleveld Sedation Target","For each participant, the median model-predicted effect-site concentration at maintenance MOAA\u002FS 3 observations divided by the Eleveld model sedation target (1.75 times the age-adjusted Ce50).","During remimazolam administration on the day of surgery",{"measure":19,"description":20,"timeFrame":17},"Age-Adjusted Residual Between-Patient Coefficient of Variation","Residual between-patient variability in the concentration associated with target sedation after adjustment for age as a continuous covariate, expressed as a coefficient of variation (%).",{"measure":22,"description":23,"timeFrame":24},"MOAA\u002FS Score","Modified Observer's Assessment of Alertness\u002FSedation (MOAA\u002FS) score, measured at baseline before remimazolam, at 1, 2, 3, 4, and 5 minutes after completion of loading, every 5 minutes during infusion, and every 5 minutes after infusion cessation until a score of 5 is reached in the operating room or PACU. Scores are also recorded at infusion cessation, end of surgery, operating-room discharge, and PACU admission. MOAA\u002FS ranges from 0 (no response to painful stimulation) to 5 (readily responds to a name spoken in a normal tone); lower scores indicate deeper sedation.","From baseline before remimazolam until MOAA\u002FS 5 after infusion cessation on the day of surgery",{"measure":26,"description":27,"timeFrame":28},"Remimazolam Infusion Rate","Remimazolam infusion rate (mg\u002Fkg\u002Fh), measured at 5-minute intervals from the end of the loading dose until infusion cessation. The rate after any adjustment at each assessment is recorded.","From the end of the remimazolam loading dose until infusion cessation on the day of surgery",{"measure":30,"description":31,"timeFrame":17},"Number of Dose Increases Before Target Sedation","Number of infusion-rate increases required before reaching target sedation (MOAA\u002FS \\\u003C=3).",{"measure":33,"description":34,"timeFrame":17},"Maintenance Infusion-Rate Distribution","Distribution of remimazolam infusion rates during maintenance, expressed in mg\u002Fkg\u002Fh.",{"measure":36,"description":37,"timeFrame":17},"Failure to Achieve Target Sedation at the Maximum Infusion Rate","Number and proportion with persistent MOAA\u002FS \\>3 at 0.8 mg\u002Fkg\u002Fh requiring discontinuation of remimazolam or a change of sedative.",{"measure":39,"description":40,"timeFrame":17},"Total Remimazolam Dose","Total intravenous remimazolam administered, in milligrams.",{"measure":42,"description":43,"timeFrame":17},"Incidence of Paradoxical Reactions","Number and proportion with agitation, increased movement, restlessness, or disinhibited speech despite increasing remimazolam infusion rates.",{"measure":45,"description":46,"timeFrame":17},"Richmond Agitation-Sedation Scale Score During Paradoxical Reactions","Richmond Agitation-Sedation Scale (RASS) scores recorded when paradoxical reactions occur. RASS ranges from -5 (unarousable) to +4 (combative), with 0 indicating alert and calm.",{"measure":48,"description":49,"timeFrame":50},"Raw EEG Data","Four-channel frontal raw electroencephalographic (EEG) signals recorded continuously using a Masimo SedLine sensor. The time-stamped signals are stored for offline analysis.","From SedLine sensor placement before sedation until operating-room discharge on the day of surgery",{"measure":52,"description":53,"timeFrame":54},"Hypoxemia","Proportion of participants with peripheral oxygen saturation (SpO2) below 95%.","During surgery and PACU recovery on the day of surgery",{"measure":56,"description":57,"timeFrame":54},"Jaw Thrust","Proportion of participants requiring a jaw-thrust maneuver to maintain airway patency.",{"measure":59,"description":60,"timeFrame":61},"Postanesthesia Care Unit Length of Stay","Elapsed time in minutes from admission to discharge from the postanesthesia care unit.","From postanesthesia care unit admission to discharge on the day of surgery",{"measure":63,"description":64,"timeFrame":65},"Patient Satisfaction With Intraoperative Sedation","Overall satisfaction with sedation rated by the participant on a 0-10 numerical scale. Higher scores indicate greater satisfaction.","Before PACU discharge on the day of surgery",{"measure":67,"description":68,"timeFrame":69},"Hypotension","Proportion of participants with mean arterial pressure below 65 mmHg.","During surgery on the day of surgery",{"measure":71,"description":72,"timeFrame":73},"Flumazenil Administration","Number and proportion of participants receiving flumazenil and frequency of administration.","During surgery and postanesthesia recovery on the day of surgery",{"measure":75,"description":76,"timeFrame":50},"Patient State Index (PSI)","Patient State Index (PSI) measured using the Masimo SedLine system. PSI is recorded continuously, with values collected at 5-minute intervals alongside intraoperative MOAA\u002FS assessments. The index ranges from 0 to 100; lower values generally indicate a deeper hypnotic state.",{"measure":78,"description":79,"timeFrame":69},"Bradycardia","Proportion of participants with heart rate below 45 beats\u002Fmin.",{"measure":81,"description":82,"timeFrame":69},"Tachycardia","Proportion of participants with heart rate above 110 beats\u002Fmin.",{"measure":84,"description":85,"timeFrame":54},"Apnea","Proportion of participants with apnea lasting at least 30 seconds, assessed by end-tidal carbon dioxide monitoring.",{"measure":87,"description":88,"timeFrame":54},"Nasopharyngeal Airway Insertion","Proportion of participants requiring insertion of a nasopharyngeal airway.",{"measure":90,"description":91,"timeFrame":54},"Oropharyngeal Airway Insertion","Proportion of participants requiring insertion of an oropharyngeal airway.",{"measure":93,"description":94,"timeFrame":54},"Positive-Pressure Ventilation","Proportion of participants requiring positive-pressure ventilation to support breathing.",{"measure":96,"description":97,"timeFrame":54},"Tracheal Intubation","Proportion of participants requiring unplanned tracheal intubation for airway or respiratory support.",{"measure":99,"description":100,"timeFrame":54},"Supplemental Oxygen Escalation","Proportion of participants requiring new or increased supplemental oxygen for a sedation-related respiratory event. Planned routine oxygen administration is not counted as an adverse-event intervention.",{"measure":102,"description":103,"timeFrame":104},"Infusion Interruption for Oversedation","Proportion of participants whose remimazolam infusion is interrupted because of oversedation (MOAA\u002FS \\\u003C=1).","During remimazolam infusion on the day of surgery",{"measure":106,"description":107,"timeFrame":108},"Nausea","Proportion of participants reporting nausea.","From remimazolam administration through 24 hours after surgery",{"measure":110,"description":111,"timeFrame":108},"Vomiting","Proportion of participants experiencing vomiting, recorded separately from nausea.",{"measure":113,"description":114,"timeFrame":108},"Hiccups","Proportion of participants experiencing hiccups.",{"measure":116,"description":117,"timeFrame":108},"Hypersensitivity Reaction","Proportion of participants experiencing a clinically identified hypersensitivity reaction.",{"measure":119,"description":120,"timeFrame":108},"Headache","Proportion of participants reporting headache.",{"measure":122,"description":123,"timeFrame":108},"Dizziness","Proportion of participants reporting dizziness.",{"measure":125,"description":126,"timeFrame":127},"Respiratory Depression in the PACU","Proportion of participants with respiratory depression identified by the clinical team during PACU recovery.","From PACU admission to PACU discharge on the day of surgery",null,{"allocation":130,"interventionModel":131,"interventionModelDescription":132,"primaryPurpose":133,"observationalModel":128,"timePerspective":128,"maskingInfo":134},"NA","SINGLE_GROUP","Single-center, prospective, single-arm, open-label study with 60 participants. Enrollment is stratified by age (19-49, 50-69, and 70 years or older; 20 participants per stratum) to ensure a balanced age distribution. All participants receive the same standardized remimazolam titration protocol. There is no randomization or comparator group; age is analyzed as a continuous covariate.","BASIC_SCIENCE",{"masking":135,"maskingDescription":128,"whoMasked":128},"NONE","This is a single-center, prospective, single-arm, open-label study with age-stratified enrollment. Age strata are used to achieve a balanced age distribution rather than to define randomized treatment groups. Age will be modeled as a continuous covariate.\n\nThe study evaluates the concentration-response relationship during standardized titrated remimazolam sedation under spinal anesthesia. The Eleveld pharmacokinetic\u002Fpharmacodynamic model will be used after surgery to reconstruct model-predicted effect-site concentrations from recorded drug administration histories and patient covariates under the no-opioid condition. Model predictions will not be provided to the treating anesthesiologist or sedation assessor during surgery. Four-channel frontal electroencephalography and processed indices will be recorded in the operating room; recovery-room assessments will use clinical sedation scores without electroencephalography.\n\nThe principal analysis will use an ordinal mixed-effects model relating model-predicted effect-site concentration to the Modified Observer's Assessment of Alertness\u002FSedation (MOAA\u002FS) score. Between-patient variability will be expressed as a coefficient of variation, with population Ce50 and confidence intervals reported for interpretation. Age-related and residual between-patient variability will be evaluated separately. Concentration phase (rising, stable, or falling) and elapsed infusion time will be considered, and sex and body weight will be examined as additional covariates.\n\nThe analysis set will include participants with at least one evaluable concentration-sedation observation. If another sedative is required after failure to reach the target at the maximum remimazolam rate, observations before the switch will remain eligible for analysis; subsequent sedation and electroencephalographic data will be excluded from the pharmacodynamic analysis. Early observations within 5 minutes after loading will be used to explore individualized prediction of later responses. Exploratory electroencephalographic analyses will assess associations of spectral and other signal features with sedation scores and model-predicted concentrations. No interim analysis or missing-data imputation is planned. Adverse events will be assessed through 24 hours after surgery.",[138],{"label":139,"type":140,"description":141,"interventionNames":142},"Titrated Remimazolam Sedation","EXPERIMENTAL","All participants undergo lower extremity surgery under spinal anesthesia and receive intravenous remimazolam titrated to a Modified Observer's Assessment of Alertness\u002FSedation (MOAA\u002FS) score of 3. A fixed 2.5 mg loading dose is administered over 1 minute, followed by 0.2 mg\u002Fkg\u002Fh. The infusion is adjusted in 0.05 mg\u002Fkg\u002Fh steps at 5-minute assessments within a range of 0.05-0.8 mg\u002Fkg\u002Fh. Infusion is stopped at the start of muscle-layer closure, and recovery is assessed until MOAA\u002FS 5. Age-stratified enrollment does not create separate treatment arms.",[143],"Drug: Remimazolam",[145],{"type":146,"name":147,"description":148,"armGroupLabels":149,"otherNames":150},"DRUG","Remimazolam","Remimazolam besylate is prepared at 1 mg\u002FmL. After spinal anesthesia, 2.5 mg is infused intravenously over 1 minute, followed by 0.2 mg\u002Fkg\u002Fh. MOAA\u002FS is assessed at 1-5 minutes after loading and then every 5 minutes. Increase by 0.05 mg\u002Fkg\u002Fh for MOAA\u002FS \\>3; decrease by 0.05 mg\u002Fkg\u002Fh for MOAA\u002FS \\\u003C=2, maintaining the minimum rate if already at 0.05 mg\u002Fkg\u002Fh. Permitted range: 0.05-0.8 mg\u002Fkg\u002Fh. Stop infusion for MOAA\u002FS \\\u003C=1 or airway\u002Frespiratory impairment; resume at the minimum rate after recovery, with flumazenil if clinically indicated. Stop remimazolam and consider another sedative if MOAA\u002FS remains \\>3 at the maximum rate. Stop infusion at the start of muscle-layer closure. Assess MOAA\u002FS every 5 minutes after cessation until MOAA\u002FS 5. Opioids and other sedatives are not coadministered during the study regimen.",[139],[151],"Byfavo",[153],{"facility":5,"status":128,"city":154,"state":128,"zip":128,"country":155,"countryCode":128,"cosmosGeoPoint":156,"geoPoint":161,"contacts":162},"Seoul","South Korea",{"type":157,"coordinates":158},"Point",[159,160],126.9784,37.566,{"lat":160,"lon":159},[163,168],{"name":164,"role":165,"phone":166,"phoneExt":128,"email":167},"Hansol Kim, MD","CONTACT","+82-2-2072-2467","hansolfrkr@gmail.com",{"name":164,"role":169,"phone":128,"phoneExt":128,"email":128},"PRINCIPAL_INVESTIGATOR",{"type":169,"investigatorFullName":164,"investigatorTitle":171,"investigatorAffiliation":5,"oldNameTitle":128,"oldOrganization":128},"Assistant Clinical Professor",[173,175],{"name":174,"class":6},"National Research Foundation of Korea",{"name":176,"class":177},"Ministry of Science and ICT, Republic of Korea","OTHER_GOV","100659360","phase-4-remimazolam-concentration-and-sedation-depth-during-lower-extremity-surgery-under-spinal-anesthesia-100659360",false,"NCT07863063","Remimazolam Concentration and Sedation Depth During Lower Extremity Surgery Under Spinal Anesthesia","Relationship Between Model-Predicted Effect-Site Concentration and Sedation Depth During Titrated Remimazolam Sedation for Lower Extremity Surgery Under Spinal Anesthesia: An Age-Stratified Prospective Study","Inclusion Criteria:\n\n* Age 19 years or older.\n* Scheduled for lower extremity surgery under spinal anesthesia.\n* American Society of Anesthesiologists (ASA) physical status I-III.\n* Agrees to intraoperative sedation and provides written informed consent.\n\nExclusion Criteria:\n\n* Refusal to participate.\n* Contraindication to spinal anesthesia, including refusal, increased intracranial pressure, infection at the puncture site, underlying neurological disease, severe hypovolemia, aortic or mitral stenosis, thrombocytopenia, or coagulopathy.\n* Contraindication or history of hypersensitivity to remimazolam, including acute narrow-angle glaucoma, severe respiratory failure, or dextran 40 hypersensitivity.\n* Contraindication or history of hypersensitivity to flumazenil.\n* Body weight below 40 kg.\n* Baseline Modified Observer's Assessment of Alertness\u002FSedation (MOAA\u002FS) score of 4 or lower.\n* Central nervous system disease or cognitive impairment that makes MOAA\u002FS assessment unreliable.\n* Regular use of psychotropic medications, including benzodiazepines.\n* Pregnancy.\n* Other circumstances judged unsuitable by the investigator.\n\nOnly adults capable of providing informed consent are included. Employees and students are not included, as specified in the protocol.","ALL","19 Years",{"count":188,"type":189},60,"ESTIMATED","INTERVENTIONAL",[192],"PHASE4","This study will examine how the amount of remimazolam predicted to reach its site of action relates to the depth of sedation during lower extremity surgery under spinal anesthesia. Remimazolam is a sedative used to help patients relax and feel sleepy during surgery. People may respond differently to the same amount of this medicine, and age may explain some of these differences.\n\nSixty adults will be enrolled at Seoul National University Hospital, with 20 participants in each age group: 19-49 years, 50-69 years, and 70 years or older. All participants will receive remimazolam using the same stepwise dose-adjustment rules. The dose will be adjusted according to repeated assessments of responsiveness. Researchers will record sedation scores, medication delivery, brain-wave signals, vital signs, recovery, and side effects.\n\nAfter surgery, a computer model will estimate the remimazolam concentration at its site of action. These estimates will not be available to the clinical team during surgery. The main goal is to measure how much the concentration associated with the target level of sedation varies between patients. The study will also examine the effect of age and whether early responses can help predict an individual patient's later response.",[195],"Sedation During Lower Extremity Surgery Under Spinal Anesthesia",[147,197,198,199,200,201],"Spinal anesthesia","Effect-site concentration","Sedation depth","Pharmacodynamics","Electroencephalography","NOT_YET_RECRUITING","2026-10-06",{"date":205,"type":206},"2026-10-13","ACTUAL",{"date":208,"type":189},"2026-10-30",{"date":210,"type":189},"2027-10",{"name":5,"class":6},1]