Adverse Drug Event, Critical Illness, Effect of Drug, Mechanical Ventilation Complication, Sedation, Surgery
Conditions
Brief summary
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.
Interventions
DRUGRemimazolam 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.
DRUGDexmedetomidine 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.
Sponsors
Beijing Shijitan Hospital, Capital Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of time in optimal sedation | Through the useage of sedative drugs in the ICU, an average of 3 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilation free days | Through the initiation of enrollment to 28 days, an average of 1 day | 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. |
| Dosage of rescue sedatives | Through the useage of sedative drugs in the ICU, an average of 3 days | Dosage of rescue sedatives during mechanical ventilation in the ICU |
| Frequency of rescue sedatives | Through the useage of sedative drugs in the ICU, an average of 3 days | Frequency of rescue sedatives during mechanical ventilation in the ICU |
| Delirium incidence | Through the ICU stay, an average of 3 days | Delirium incidence during the patients' ICU stay, assessed using ConfusionAssessmentMethodfortheIntensive CareUnit(CAM-ICU, 4 items), delirium is diagnosed when 3 items are met |
| post-sedation extubation time | From ICU admission to extubation, an average of 3 days | Extubation time(hour) after termination of sedation |
| Re-mechanical ventilation incidence after weaning and extubation | Through the ICU stay, an average of 3 days | Re-mechanical ventilation incidence after weaning and extubation |
| Proportion of different oxygen therapies post-extubation | Through the ICU stay, an average of 3 days | Proportion of different oxygen therapies post-extubation |
| Pain scores during the first 3 postoperative days | The first 3 days of ICU stay, an average of 3 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 |
| Sleep quality scores on the day of ICU discharge | The day transfer out of ICU, an average of 1day | 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 |
| Cognitive assessment scores on postoperative day 60 | Day 60 after surgery, an average of 1 day | 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 |
| Sleep quality scores on postoperative day 60 | Day 60 after surgery, an average of 1 day | 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 |
| ICU LOS | The day the patient transfer out of ICU, an average of 1 day | ICU length of stay |
| Postoperative hospital LOS | The day the patient discharge, an average of 1 day | postoperative hospital length of stay |
| 60-day all-cause mortality | Day 60 postoperative, an average of 1 day | 60-day all-cause mortality |
| 60-day non-neurological complications | Day 60 postoperative, an average of 1 day | 60-day non-neurological complications |
Countries
China
Contacts
CONTACTYuefu Wang, doctor
CONTACTDandan Liu, doctor
STUDY_CHAIRJianxin Zhou, doctor
Beijing Shijitan Hospital, Capital Medical University
Outcome results
None listed