The Availability and Safety Study of Remimazolam Besylate for Injection on Sedation of ERAS Patients

Study Overview
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Brief Summary
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This trial intends to evaluate Remimazolam Besylate's availability and safety compared with propofol.

Official Title
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The Availability and Safety Study of Remimazolam Besylate for Injection on Sedation of ERAS Patients Under Mechanical Ventilation in ICU: Protocol for a Randomized, Open-label, Controlled Trial

Conditions
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Analgesia, Postoperative Pain

Intervention / Treatment
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* Drug: Remimazolam Besylate
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Meet criteria of enhanced recovery after surgery (ERAS); Mechanical ventilated when enrolled and have estimation of more than 10 hours of mechanical ventilation in ICU Aged between 18-75 years old AND 18kg/m2 ≤ BMI ≤ 30 kg/m2; Clearly know the purpose and objective of this clinical study and voluntarily enrolled. Criteria of ERAS: (1) without dysfunction of nervous system or Glasgow Coma Score > 12; (2) a satisfied glucose level (random blood glucose<11.1mmol/L during screening stage) for diabetes mellitus patients; (3) Without acute coronary syndrome in recent 6 months; (4) Without bradycardia and third-degree atrioventricular block (except for patients with pacemaker) during screening stage; (5) systolic blood pressure>90mmHg with no usage of vasoactive agent during screening stage; (6) without mental illness (schizophrenia, depressive disorder), cognitive dysfunction (identified by MMSE), epilepsy, history of abuse of psychotropic or anesthesia medication; (7) without disorder of coagulation function (PT/INR/APTT > 1.5×upper limit), bleeding tendency (active peptic ulcer), under treatment of thrombolysis and anticoagulant; (8) without disorder of liver function (ALT/AST > 2×upper limit and total bilirubin>1.5×upper limit); (9) without disorder of renal function (Creatine or BUN/Urea>1.5×upper limit); without dialysis patients. Exclusion criteria Allergy to component of Remimazolam besylate for injection; Woman in gestation and lactation period; Enrolled in other clinical trails in recent 3 months; Other circumstance that identified by researchers that do not suitable for this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group: Remimazolam Besylate<br>Patients should be given study drugs as soon as possible after entering the ICU. Syringe pump is used to administer medication. Loading dose of Remimazolam is 0.2 mg/kg, which is administered for less than 1 min initially. Maintaining dose is 0.2-1 mg/kg/h. Sedative target is RASS between 0 and -2 points. Excepts for fentanyl and Remimazolam, no analgesic or sedative could be used during the experimental time period. | Drug: Remimazolam Besylate<br>* Remimazolam Besylate are used as sedatives for subjects in this arm.<br>|
| Active Comparator: Positive control group: Propofol<br>Patients should be given study drugs as soon as possible after entering the ICU. Syringe pump is used to administer medication. Loading dose of propofol is 0.2 mg/kg, which is administered for less than 1 min initially. Maintaining dose is 0.3-4.0 mg/kg/h. Sedative target is RASS between 0 and -2 points. Excepts for fentanyl and propofol, no analgesic or sedative could be used during the experimental time period. Rescue therapy for experimental group During the treatment of the experimental group, if the RASS cannot be maintained at 0 to -2 points at the maximum Remimazolam maintenance dose of 1 mg/kg/h, a loading dose of propofol (0.2 mg/kg) can be given intravenously. If RASS fails to satisfied after three loading doses of propofol, Remimazolam is discarded and 0.3-4.0 mg/kg/h of propofol are used as rescue therapy for experimental group. | Drug: Propofol<br>* Propofol are used as sedatives for subjects in this arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Satisfaction rate of sedation | (number of subjects that meets satisfied RASS score under prescribed dose of sedative agents during study / total number of subjects) ×100% | 24 hours since injection of sedatives | 
| Rate of major clinical events | (number of subjects that suffer from major clinical events during study / total number of subjects) ×100%. Major clinical events are defined as cardiac arrest, malignant arrhythmia, new onset of shock, new onset of sepsis and respirate failure unrelated to primary illness. | 48 hours since injection of sedatives | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of delirium | (subjects with delirium / total number of subjects ×100%) by 12h and 24h after entering ICU | 48 hours since injection of sedatives | 
| Time to weaning and extubation | Time to weaning and extubation | 48 hours since injection of sedatives | 
| Difficulty of nursing | By Barthel index assessment | 48 hours since injection of sedatives | 
| 28-days survival | (number of subjects that alive in 28-days since ICU entry/ total number of subjects) ×100% | 28 days since injection of sedatives | 
| incidence of rescue therapy in experimental group | (number of subjects that receive rescue therapy in experimental group/ total number of subjects) ×100% | 24 hours since injection of sedatives | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sedative, Remimazolam Besylate, postoperative sedation