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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| remimazolam besylate group | Experimental | 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. |
|
| Dexmedetomidine hydrochloride group | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remimazolam Besylate | Drug | 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. |
| 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 |
| 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,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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yuefu Wang, doctor | Contact | +86 | 15301306289 | wangyuefu3806@bjsjth.cn |
| Dandan Liu, doctor | Contact | +86 | 13810589291 | ldd3967@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Jianxin Zhou, doctor | Beijing Shijitan Hospital, Capital Medical University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Shijitan Hospital.CMU | Recruiting | Beijing | Beijing Municipality | 100038 | China |
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| Dexmedetomidine Hydrochloride | Drug | 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. |
|
| 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 |
| 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 |
| post-sedation extubation time | 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 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 |
| ICU LOS | ICU length of stay | The day the patient transfer out of ICU, 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 |
| ID | Term |
|---|---|
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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