Efficacy and Safety of Remimazolam Besylate for Sedation in Post-Non-Cardiac Surgery Patients Requiring Mechanical Ventilation

Efficacy and Safety of Remimazolam Besylate for Sedation in Post-Non-Cardiac Surgery Patients Requiring Mechanical Ventilation: A Randomized Controlled Trial

A multi-center, prospective, randomized, double-blind, active-controlled, no-inferiority clinical trial conducted across 5 tertiary medical centers in China. The objective of this RCT is to evaluate the sedative efficacy and safety profile of remimazolam besylate compared with dexmedetomidine in patients requiring mechanical ventilation following non-cardiac surgery. The study hypothesized that remimazolam besylate is non-inferior to dexmedetomidine regarding the primary efficacy outcome.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Surgery; Sedation; Mechanical Ventilation Complication; Adverse Drug Event; Effect of Drug
• Intervention / Treatment: Drug: Remimazolam Besylate; Drug: Dexmedetomidine Hydrochloride

• Study Type: Interventional
• Enrollment (Estimated): 306
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yuefu Wang, doctor; Phone Number: 15301306289 +86; Email: wangyuefu3806@bjsjth.cn
• Study Contact Backup: Name: Dandan Liu, doctor; Phone Number: 13810589291 +86; Email: ldd3967@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100038
      • Recruiting
      • Beijing Shijitan Hospital.CMU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged between 18 and 64 years
• Scheduled to undergo elective non-cardiac surgery
• Planned for general anesthesia
• With or without combined regional nerve blockade
• Admitted to the ICU with endotracheal intubation post-surgery
• With an anticipated duration of postoperative mechanical ventilation greater than 24 hours
• Clinically requiring light sedation( target RASS score 0 to -2)

Exclusion Criteria:

• Undergoing intracranial surgery, or having a history of severe neurological or spinal cord diseases
• Pre-existing history of schizophrenia, epilepsy, or Parkinson's disease
• Inability to communicate preoperatively due to coma, severe dementia, or language barriers
• Preoperative .cardiac insufficiency or severe cardiac arrhythmias
• Severe hepatic impariment( Child-Pugh class C)
• Severe renal impariment
• Preoperative( within 24 hours prior to surgery) or intraoperative administration of dexmedetomidine or remimazolam
• Pregnancy or lactation
• Participation in any clinical trial involving investigational drugs within 30 days prior to enrollment
• Any other conditions deemed by the investigators to render the patient unsuitable for study participation
• Refusal to provide written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: remimazolam besylate group; Upon ICU admission, remimazolam besylate infusion will initiated for light sedation maintenance at a dose range of 0.1 to1.0mg/Kg/h. The target sedation depth is defined as a RASS score of 0 to -2. The RASS score will evaluated and recorded hourly, and the infusion rate of remimazolam besylate will titrated( increased or decreased) accordingly to maintain the patient within the target sedation range. For multimodal analgesia, remifentanil will co-administered continuously at a dose of 0.1 to 0.5ug/Kg/min to ensure a CPOT score of 2 or less.	Drug: Remimazolam Besylate; patients will be sedated with remimazolam via intravenous pump on the day of ICU admission, the dosage will titrate with the depth of sedation evaluated with RASS. If the target sedation depth could not to achieved within the prespecified maximum dose range of remimazolam, a standardized rescue sedation protocol will intiated as follows: an intravenous bolus of propofol at 0.2mg/kg will administered. Sedation depth will evaluated 5 minutes post-injection. The identical dose of propofol bolus will repeated until the desired sedation depth is reached. Continuous propofol infusion will initiated after three consecutive bolus injections of propofol. The continuous propofol infusion rate will titrated within the range of 0.2 to 1.0 mg/kg/h until the satisfactory target sedation depth is established. At the subsequent hourly sedation assessment, continuous propofol infusion will discontinued once the patient successfully maintained a stable RASS score within the 0 to -2 range.
Active Comparator: Dexmedetomidine hydrochloride group; Upon ICU admission, dexmedetomidine infusion will initiated for light sedation maintenance at a dose range of 0.2 to0.7ug/Kg/h. The target sedation depth is defined as a RASS score of 0 to -2. The RASS score will evaluated and recorded hourly, and the infusion rate of dexmedetomidine will titrated( increased or decreased) accordingly to maintain the patient within the target sedation range. For multimodal analgesia, remifentanil will co-administered continuously at a dose of 0.1 to 0.5ug/Kg/min to ensure a CPOT score of 2 or less.	Drug: Dexmedetomidine Hydrochloride; patients will be sedated with dexmedetomidine hydrochloride via intravenous pump on the day of ICU admission, the dosage will titrate with the depth of sedation evaluated with RASS. If the target sedation depth could not to achieved within the prespecified maximum dose range of remimazolam, a standardized rescue sedation protocol will intiated as follows: an intravenous bolus of propofol at 0.2mg/kg will administered. Sedation depth will evaluated 5 minutes post-injection. The identical dose of propofol bolus will repeated until the desired sedation depth is reached. Continuous propofol infusion will initiated after three consecutive bolus injections. The continuous propofol infusion rate will titrated within the range of 0.2 to 1.0 mg/kg/h until the satisfactory target sedation depth is established. At the subsequent hourly sedation assessment, continuous propofol infusion will discontinued once the patient successfully maintained a stable RASS score within the 0 to -2 range.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time in optimal sedation	Percentage of time in optimal sedation during sedation in the ICU, sedation depth is assessed using Richmond Agitation Sedation Scale(RASS, -5 to +4), target sedation must has a RASS score -2 to 0.	Through the useage of sedative drugs in the ICU, an average of 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium incidence	Delirium incidence during the patients' ICU stay, assessed using ConfusionAssessmentMethodfortheIntensive CareUnit(CAM-ICU, 4 items), delirium is diagnosed when 3 items are met	Through the ICU stay, an average of 3 days
Re-mechanical ventilation incidence after weaning and extubation	Re-mechanical ventilation incidence after weaning and extubation	Through the ICU stay, an average of 3 days
ICU LOS	ICU length of stay	The day the patient transfer out of ICU, an average of 1 day
Ventilation free days	Ventilation free days(VFDs) at 28 days. VFDs=0 if subject dies within 28 days of mechaincal ventilation; VFDs=28-X if successfully liberated from ventilation X days after initiation，if the patient is reintubated within 28 days, "X" represents the days of the last extubation; VFDs=0 if the subject is mechaincally ventilated for >28 days.	Through the initiation of enrollment to 28 days, an average of 1 day
Dosage of rescue sedatives	Dosage of rescue sedatives during mechanical ventilation in the ICU	Through the useage of sedative drugs in the ICU, an average of 3 days
Frequency of rescue sedatives	Frequency of rescue sedatives during mechanical ventilation in the ICU	Through the useage of sedative drugs in the ICU, an average of 3 days
post-sedation extubation time	Extubation time(hour) after termination of sedation	From ICU admission to extubation, an average of 3 days
Proportion of different oxygen therapies post-extubation	Proportion of different oxygen therapies post-extubation	Through the ICU stay, an average of 3 days
Pain scores during the first 3 postoperative days	Pain scores during the first 3 postoperative days, assessed using Critical-Care Pain Observation Tool(CPOT,0-8), the higher the score, the more painful the patient feels	The first 3 days of ICU stay, an average of 3 days
Sleep quality scores on the day of ICU discharge	Sleep quality scores on the day of ICU discharge, assessed using St.Mary'sHospitalSleepQuestionnaire(SMHSQ, 11 to 55), the lower the score, the higher the degree of sleep disorders	The day transfer out of ICU, an average of 1day
Cognitive assessment scores on postoperative day 60	Cognitive assessment scores on postoperative day 60, assessed using Telephone Interview for Cognitive Status-Modified(TICS-m,0-50), the higher the score, the better the cognitive function	Day 60 after surgery, an average of 1 day
Sleep quality scores on postoperative day 60	Sleep quality scores on postoperative day 60 assessed using Pittsburgh sleep quality index(PSQI,0-21), the higher the score, the worse the sleep quality	Day 60 after surgery, an average of 1 day
Postoperative hospital LOS	postoperative hospital length of stay	The day the patient discharge, an average of 1 day
60-day all-cause mortality	60-day all-cause mortality	Day 60 postoperative, an average of 1 day
60-day non-neurological complications	60-day non-neurological complications	Day 60 postoperative, an average of 1 day

Collaborators and Investigators

• Sponsor: Beijing Shijitan Hospital, Capital Medical University
• Investigators: Study Chair: Jianxin Zhou, doctor, Beijing Shijitan Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Actual): May 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: August 11, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 13, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Chemically-Induced Disorders; Pathological Conditions, Signs and Symptoms; Critical Illness; Drug-Related Side Effects and Adverse Reactions; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Dexmedetomidine
• Other Study ID Numbers: IIT2024-001-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No