Sedation Efficacy and Safety of Remazolam Besylate in Ventilated Surgical Critically Ill Patients

Efficacy and Safety of Remazolam Besylate in Patients Requiring Mechanical Ventilation Admitted to ICU After Non-cardiac Surgery: Protocol for a Randomized, Controlled No-inferiority Trial

A multi-center, prospective, randomized, double-blind, no-inferiority clinical trial designed to assess the the safety and efficacy of remazolam besylate in sedation of critically ill mechanically ventilated patients after surgery compared to dexmedetomidine.

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, master; 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:

• 18-64 years old
• must accept no-cardiac elective surgery
• must under general anaesthesia
• can be combined regional tissue anesthesia
• must admitted to ICU with tracheal intubation after general anaesthesia - expected mechanical ventilation time must more than 24 hours
• light or moderate sedation must needed

Exclusion Criteria:

• intracranial surgery or severe neurological or spinal cord disease
• schizophrenia, epilepsy, and Parkinson's disease
• coma, severe dementia, or language barrier before surgery
• cardiac dysfunction or arrhythmia
• severe liver dysfunction(Child-Pugh C class)
• severe kidney dysfunction
• use of dexmedetomidine or remifentanil besylate 24 hours before or during surgery
• pregnancy or lactation
• any investigational drug useage 30 days before surgery
• refuse to participant.

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; Light sedation will started when the patient admitted to ICU after non-cardiac surgery under general anesthesia with remimazolam besylate which will continuously intravenously pumped at a rate of 0.2-1.0mg/kg/h . Depth of sedation will assessed by RASS hourly to ensure a RASS score of 0 to -2. Adjust the dosage of remimazolam (increase or decrease) based on the RASS score. At the same time, use remifentanil (0.1-0.5/kg/min) as a combination analgesic drug to ensure that the CPOT is ≤2 points. When a satisfactory level of RASS score (0 to -2 points) is still not achieved within the upper limit of remimazolam, a remedial sedation will started using propofol. Researchers assess the patient daily during the ICU stay whether to terminate sedative drug, weaning and extubation, and compete the outcomes assessment.	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. A remedial sedation protocol will be initiated if remimazolam fails to achieve a satisfactory RASS score (0 to -2 points) within its upper dosage limits, propofol will be administered intravenously at a dose of 0.2 mg, followed by reassessment 5 minutes post-injection. The same dose of propofol will be repeated if the desired sedation depth is not reached. Continuous infusion of propofol will be started at a rate of 0.2 to 1 mg/kg/h if satisfactory sedation is not attained after three consecutive intravenous injections of propofol, the continuous infusion will be discontinued once the RASS score reaching the acceptable range (0 to -2).
Active Comparator: Dexmedetomidine hydrochloride group; Light sedation will started when the patient admitted to ICU after non-cardiac surgery under general anaesthesia with dexmedetomidine, which will continuously intravenously pumped at a rate of 0.2-0.7ug/kg/h. Depth of sedation will assessed by RASS hourly to ensure a RASS score of 0 to -2. Adjust the dosage of dexmedetomidine (increase or decrease) based on the RASS score. At the same time, use remifentanil (0.1-0.5/kg/min) as a combination analgesic drug to ensure that the CPOT is ≤2 points. When a satisfactory level of RASS score (0 to -2 points) is still not achieved within upper limit of dexmedetomidine, a remedial sedation will started using propofol. Researchers assess the patient daily during the ICU stay whether to terminate sedative drug, weaning and extubation, and compete the outcomes assessment.	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. A remedial sedation protocol will be initiated if dexmedetomidine fails to achieve a satisfactory RASS score (0 to -2 points) within the upper dosage limits, propofol will be administered intravenously at a dose of 0.2 mg, followed by reassessment 5 minutes post-injection. The same dose of propofol will be repeated if the desired sedation depth is not reached. Continuous infusion of propofol will be started at a rate of 0.2 to 1 mg/kg/h if satisfactory sedation is not attained after three consecutive intravenous injections of propofol, the continuous infusion will be discontinued once the RASS score reaching the acceptable range (0 to -2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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; VFDs=0 if the subject is mechaincally ventilated for >28 days.	Through the initiation of enrollment to 28 days, an average of 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosage of remedial sedatives	Dosage of remedial sedatives during mechanical ventilation in the ICU	Through the useage of sedative drugs in the ICU, an average of 3 days
Frequency of remedial sedatives	Frequency of remedial sedatives during mechanical ventilation in the ICU	Through the useage of sedative drugs in the ICU, an average of 3 days
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
Extubation time after termination of sedation	Extubation time(hour) after termination of sedation	From ICU admission to extubation, 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
Proportion of different oxygen therapies after extubation	Proportion of different oxygen therapies after extubation	Through the ICU stay, an average of 3 days
Pain assessment score the first 3 days after surgery	Pain assessment score the first 3 days after surgery, 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 score the day transfer out of ICU	Sleep quality score the day transfer out of ICU, 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 score 60 days after surgery	Cognitive assessment score 60 days after surgery, 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 score 60 days after surgery	Sleep quality score 60 days after surgery, 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
ICU LOS	ICU length of stay	The day the patient transfer out of ICU, an average of 1 day
Hospital LOS after surgery	Hospital length of stay after surgery	The day the patient discharge, an average of 1 day
All cause mortality 60 days after surgery	All cause mortality 60 days after surgery	Day 60 after surgery, an average of 1 day
Non-neurological complications 60 days after surgery	Non-neurological complications 60 days after surgery	Day 60 after surgery, an average of 1 day
Proportional of predicted sedation time	Proportional of predicted sedation time during sedation time in the ICU, sedation depth is assessed using Richmond Agitation Sedation Scale(RASS, -5 to +4), predicted sedation must has a RASS score -2 to 0.	Through the useage of sedative drugs in the ICU, an average of 3 days

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 (Estimated): April 20, 2026
• Study Completion (Estimated): June 20, 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): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: February 1, 2025

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