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

Phase 4RecruitingNCT06575530

Beijing Shijitan Hospital, Capital Medical University306 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

306

Conditions

Effect of Drug Adverse Drug Event Mechanical Ventilation Complication Critical Illness Surgery

Interventions

Remimazolam BesylateDRUG

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.

Dexmedetomidine HydrochlorideDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Through the useage of sedative drugs in the ICU, an average of 3 days

Secondary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Through the ICU stay, an average of 3 days

post-sedation extubation time

Extubation time(hour) after termination of sedation

Time frame: From ICU admission to extubation, an average of 3 days

Re-mechanical ventilation incidence after weaning and extubation

Time frame: Through the ICU stay, an average of 3 days

Proportion of different oxygen therapies post-extubation

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 60 after surgery, an average of 1 day

ICU LOS

ICU length of stay

Time frame: The day the patient transfer out of ICU, an average of 1 day

Postoperative hospital LOS

postoperative hospital length of stay

Time frame: The day the patient discharge, an average of 1 day

60-day all-cause mortality

Time frame: Day 60 postoperative, an average of 1 day

60-day non-neurological complications

Time frame: Day 60 postoperative, an average of 1 day

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts