A Phase 4 interventional study of Remimazolam and Propofol in Spinal Cord Neoplasms and Spinal Neoplasms, sponsored by Beijing Tsinghua Chang Gung Hospital. Not yet recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-28.
Sponsored by Beijing Tsinghua Chang Gung Hospital · Phase 4, Interventional, and Treatment
Intraoperative neurophysiological monitoring (IONM) using motor evoked potentials (MEP) and somatosensory evoked potentials (SEP) is routinely applied during spinal tumor resection to detect impending neurological injury. Propofol-based total intravenous anesthesia suppresses MEP amplitude in a dose-dependent manner, which can generate false-positive alerts and complicate interpretation of IONM signals. Remimazolam is an ultra-short-acting benzodiazepine whose effect on evoked potentials during spine surgery has not been well characterized.
This prospective, single-center, randomized, parallel-group, superiority trial compares remimazolam-based versus propofol-based total intravenous anesthesia in adults undergoing elective spinal tumor resection with combined MEP and SEP monitoring. The primary hypothesis is that remimazolam better preserves MEP amplitude than propofol during the critical period of tumor manipulation.
A total of 190 participants will be randomized 1:1. The primary outcome is the mean MEP amplitude of target muscles recorded during the critical period of tumor manipulation, expressed as a percentage of the pre-incision baseline value. The key secondary outcome is the incidence of intraoperative IONM alert events. Participants are followed for 30 days after surgery.
BACKGROUND
Intraoperative neurophysiological monitoring (IONM), combining transcranial motor evoked potentials (MEP) and somatosensory evoked potentials (SEP), is widely used during spinal tumor resection to identify impending spinal cord injury at a reversible stage. Both MEP and SEP are sensitive to anesthetic technique. Propofol-based total intravenous anesthesia (TIVA) is commonly used for MEP monitoring, but propofol reduces MEP amplitude in a dose-dependent manner, which may lead to false-positive alerts, unnecessary interruption of surgery, or a reduction in anesthetic depth to preserve signals. Remimazolam is a novel ultra-short-acting benzodiazepine with an organ-independent esterase metabolism and a rapid, predictable offset. Small crossover and observational studies suggest remimazolam may preserve MEP amplitude, but adequately powered parallel-group randomized evidence in spinal tumor surgery is lacking.
OBJECTIVES
Primary: to determine whether remimazolam-based TIVA preserves MEP amplitude better than propofol-based TIVA during the critical period of tumor manipulation in patients undergoing elective spinal tumor resection.
Key secondary: to compare the incidence of intraoperative IONM alert events between the two anesthetic regimens.
DESIGN
Prospective, single-center, randomized, parallel-group, superiority trial with participant and outcome-assessor blinding. The anesthesia provider performing the intervention is not blinded for safety reasons; the statistician analyzing the data is blinded to group allocation.
Randomization: stratified block randomization with stratification by tumor location (intramedullary, extramedullary intradural, epidural). Randomly permuted blocks of size 4 or 6 are generated using SPSS 26.0 by an independent statistician. Allocation is concealed in sequentially numbered, opaque, sealed envelopes opened immediately before induction of anesthesia.
PARTICIPANTS AND SETTING
190 participants (95 per group) undergoing elective spinal tumor resection at Beijing Tsinghua Chang Gung Hospital.
INTERVENTIONS
Remimazolam arm: induction with remimazolam 0.2-0.3 mg/kg intravenously, maintenance infusion 1-2 mg/kg/h.
Propofol arm: induction with propofol 1.5-2.5 mg/kg intravenously, maintenance infusion 4-6 mg/kg/h.
Both arms receive identical co-interventions: sufentanil 0.3-0.5 micrograms/kg at induction, remifentanil 0.08-0.15 micrograms/kg/min for maintenance, and a single dose of rocuronium 0.6 mg/kg at induction with no intraoperative top-up. Depth of anesthesia is titrated to a bispectral index of 40-60. Train-of-four ratio is confirmed to be at least 0.9 before baseline IONM recording. Core temperature is maintained at 36.0-37.5 degrees Celsius. Mean arterial pressure is maintained within 10 percent of baseline and not below 80 mmHg, and heart rate between 50 and 100 beats per minute, using vasoactive agents as required.
OUTCOME MEASURES
Primary: mean MEP amplitude of target muscles during the critical period of tumor manipulation (time points T2 to T4), expressed as a percentage of the baseline (T0) amplitude, that is, the MEP amplitude preservation ratio.
Key secondary: incidence of intraoperative IONM alert events, defined as a decrease in MEP amplitude of 50 percent or more from baseline, or prolongation of SEP latency of 10 percent or more.
Other secondary: change in SEP N20 or P37 latency and amplitude; change rate of MEP amplitude; coefficient of variation of MEP amplitude; intraoperative hemodynamics including mean arterial pressure, heart rate and vasoactive drug requirement; time to extubation; post-anesthesia care unit length of stay; Quality of Recovery-15 score on postoperative days 1 and 2; Japanese Orthopaedic Association score before surgery and at postoperative days 1 and 30; and incidence of adverse and serious adverse events.
Exploratory: correlation between the coefficient of variation of MEP amplitude and change in the Japanese Orthopaedic Association score, assessed by Spearman correlation.
SAMPLE SIZE
Based on an anticipated standardized effect size of 0.50 for the primary endpoint, a two-sided alpha of 0.05 and 90 percent power, 85 participants per group are required. Allowing for a 10 percent dropout rate, 95 participants per group (190 in total) will be enrolled. A blinded internal pilot re-estimation of the effect size will be performed when approximately 50 percent of participants have completed the primary endpoint assessment. If the observed effect size is below 0.40, the sample size assumption will be reassessed with the steering committee; if it is between 0.40 and 0.50, enrollment may be extended up to 148 per group; if it is at least 0.50, the planned sample size of 95 per group will be retained.
STATISTICAL ANALYSIS
The primary analysis will follow the intention-to-treat principle, with a per-protocol analysis as a sensitivity analysis. The primary endpoint will be analyzed using analysis of covariance with adjustment for baseline MEP amplitude, tumor type, tumor level, age and body mass index. The superiority margin is zero, that is, any statistically significant difference in favor of remimazolam will support superiority. Continuous secondary endpoints will be compared using t-tests or Mann-Whitney U tests as appropriate; categorical endpoints using chi-square or Fisher exact tests. Analyses will be performed using SAS 9.4 or R version 4.3.x, with SPSS 26.0 for randomization.
STUDY DURATION
Total duration of 16 months, with 12 months of enrollment and 30-day postoperative follow-up, including an internal pilot re-estimation at approximately 50 percent enrollment.
105 studies on the registry are indexed under Spinal Cord Neoplasms; 27 are open to participants now.
This study's planned enrollment of 190 is above the median of 50 across 69 interventional studies indexed under Spinal Cord Neoplasms.
Browse Spinal Cord Neoplasms studies →Beijing Tsinghua Chang Gung Hospital is the lead sponsor of 108 studies on the registry; 56 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Remimazolam is administered for induction of anesthesia at 0.2-0.3 mg/kg intravenously and for maintenance by continuous infusion at 1-2 mg/kg/h, titrated to a bispectral index of 40-60. Depth of anesthesia, analgesia and neuromuscular blockade are standardized identically in both arms: sufentanil 0.3-0.5 micrograms/kg at induction, remifentanil 0.08-0.15 micrograms/kg/min for maintenance, and a single dose of rocuronium 0.6 mg/kg at induction with no intraoperative top-up. Core temperature is maintained at 36.0-37.5 degrees Celsius, mean arterial pressure within 10 percent of baseline and not below 80 mmHg, and heart rate between 50 and 100 beats per minute.
Drug: Remimazolam
Propofol is administered for induction of anesthesia at 1.5-2.5 mg/kg intravenously and for maintenance by continuous infusion at 4-6 mg/kg/h, titrated to a bispectral index of 40-60. Depth of anesthesia, analgesia and neuromuscular blockade are standardized identically in both arms: sufentanil 0.3-0.5 micrograms/kg at induction, remifentanil 0.08-0.15 micrograms/kg/min for maintenance, and a single dose of rocuronium 0.6 mg/kg at induction with no intraoperative top-up. Core temperature is maintained at 36.0-37.5 degrees Celsius, mean arterial pressure within 10 percent of baseline and not below 80 mmHg, and heart rate between 50 and 100 beats per minute.
Drug: Propofol
Intravenous remimazolam administered for induction of general anesthesia at 0.2-0.3 mg/kg and maintained by continuous infusion at 1-2 mg/kg/h, titrated to a bispectral index of 40-60 throughout surgery.
Intravenous propofol administered for induction of general anesthesia at 1.5-2.5 mg/kg and maintained by continuous infusion at 4-6 mg/kg/h, titrated to a bispectral index of 40-60 throughout surgery.
MEP amplitude preservation ratio during the critical period of tumor manipulation
Mean motor evoked potential (MEP) amplitude of the target muscles recorded during the critical period of tumor manipulation (time points T2 to T4), expressed as a percentage of the baseline (T0) amplitude. Baseline MEP amplitude is recorded after induction of anesthesia and before surgical incision, with a train-of-four ratio of at least 0.9. The primary analysis uses analysis of covariance with adjustment for baseline MEP amplitude, tumor type, tumor level, age and body mass index, under the intention-to-treat principle, with a per-protocol sensitivity analysis. The superiority margin is zero.
Time frame: Intraoperative: from the baseline recording (after induction of anesthesia and before surgical incision) through the end of tumor manipulation
Incidence of intraoperative neurophysiological monitoring alert events
Proportion of participants with at least one intraoperative neurophysiological monitoring alert event, defined as a decrease in MEP amplitude of 50 percent or more from baseline, or prolongation of somatosensory evoked potential latency of 10 percent or more from baseline.
Time frame: Intraoperative: from the baseline recording after induction of anesthesia to the end of surgery
Change in somatosensory evoked potential N20 or P37 latency and amplitude
Change from baseline in the latency and amplitude of the cortical somatosensory evoked potential component (N20 for upper-limb stimulation or P37 for lower-limb stimulation), expressed as a percentage of the baseline value.
Time frame: Intraoperative: from the baseline recording after induction of anesthesia to the end of surgery
Rate of change and variability of motor evoked potential amplitude
Absolute and percentage change in MEP amplitude from baseline at each intraoperative time point, and the coefficient of variation of MEP amplitude across the monitoring period.
Time frame: Intraoperative: from the baseline recording after induction of anesthesia to the end of surgery
Intraoperative hemodynamic variables and vasoactive drug requirement
Mean arterial pressure, heart rate, and cumulative dose of vasoactive agents required to maintain mean arterial pressure within 10 percent of baseline and not below 80 mmHg.
Time frame: Intraoperative: from induction of anesthesia to the end of surgery
Time to extubation and post-anesthesia care unit length of stay
Time from discontinuation of the anesthetic infusion to tracheal extubation, and duration of stay in the post-anesthesia care unit.
Time frame: From the end of surgery to discharge from the post-anesthesia care unit, up to 24 hours
Quality of recovery assessed by the Quality of Recovery-15 questionnaire
Total score of the Quality of Recovery-15 (QoR-15) questionnaire, ranging from 0 to 150, with higher scores indicating better quality of recovery.
Time frame: Postoperative day 1 and postoperative day 2
Neurological function assessed by the Japanese Orthopaedic Association score
Japanese Orthopaedic Association (JOA) score assessed before surgery and after surgery; lower scores indicate greater neurological impairment. The change from baseline and its correlation with intraoperative MEP variability are evaluated.
Time frame: Before surgery, postoperative day 1, and postoperative day 30
Incidence of adverse events and serious adverse events
Number and proportion of participants experiencing treatment-emergent adverse events and serious adverse events, coded by preferred term and system organ class.
Time frame: From induction of anesthesia through postoperative day 30
Plan to share: Yes — De-identified individual participant data that underlie the results reported in the primary publication will be shared, together with the study protocol, statistical analysis plan and informed consent form. Data will be available for researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Data will become available 12 months after publication of the primary results and will remain available for 36 months thereafter.
Access criteria: Investigators who wish to access the data must submit a methodologically sound proposal to the corresponding author (whta01956@btch.edu.cn). Proposals will be reviewed by the sponsor and the study steering committee, and approval will require a signed data access agreement. Requests should be directed to the Department of Anesthesiology, Beijing Tsinghua Chang Gung Hospital.
Start is estimated for Jan 2027; primary completion for Jan 2028, 12 months later.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Remimazolam
Beijing Tsinghua Chang Gung Hospital →