Efficacy, Safety, and Pharmacokinetics of Remimazolam Besylate in Patients Receiving Short-term Sedation

Study Overview
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Brief Summary
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This is a Phase II, dose-escalation clinical trial conducted in mechanically ventilated patients receiving sedation no longer than 24 hours. The efficacy, safety, and pharmacokinetics of remimazolam besylate were evaluated using a randomized, single-blind design.

Official Title
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A Randomized Study of the Efficacy, Safety, and Pharmacokinetics of Remimazolam Besylate in Mechanically Ventilated Patients Receiving Short-term Sedation

Conditions
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Mechanically Ventilated Patients

Intervention / Treatment
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* Drug: Remimazolam besylate
* Drug: Remimazolam besylate
* Drug: Remimazolam besylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≥18 and ≤ 30 kg/m2 Being Intubated and mechanically ventilated ≤48 hours before enrollment and expected to be on a ventilator for at least 6 hours Requirement for light to moderate sedation (a Richmond agitation-sedation scale score of -2 to 1) Exclusion Criteria: Refusal to be included Allergy or unsuitability to any composition of study drugs or remifentanil Living expectancy less than 48 hours Myasthenia gravis Status asthmaticus Abdominal compartment syndrome Serious hepatic dysfunction (CTP 10-15); Chronic kidney disease with glomerular filtration rate (GFR) < 29 ml/min/1.73m2 Mean blood pressure less than 65 mm Hg or the need for a continuous infusion of norepinephrine at ≥0.5 ug/kg/min to maintain Mean blood pressure ≥ 65 mm Hg Possible requirement for surgery or bedside tracheostomy in 24 hours Possible requirement for renal replacement therapy in 24 hours Acute severe neurological disorder and any other condition interfering with sedation assessment Abuse of controlled substances or alcohol Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Small dose<br> | Drug: Remimazolam besylate<br>* After a loading dose of 0.08mg/kg, a maintaining dose of 0.1mg/kg/h is given<br>* Other names: A maintaining dose of 0.1mg/kg/h;|
| Experimental: Medium dose<br> | Drug: Remimazolam besylate<br>* After a loading dose of 0.08mg/kg, a maintaining dose of 0.2mg/kg/h is given<br>* Other names: A maintaining dose of 0.2mg/kg/h;|
| Experimental: Large dose<br> | Drug: Remimazolam besylate<br>* After a loading dose of 0.08mg/kg, a maintaining dose of 0.4mg/kg/h is given<br>* Other names: A maintaining dose of 0.4mg/kg/h;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of time in the target sedation range without rescue sedation | The percentage of time in the target sedation range without rescue sedation | Within 24 hours while receiving the study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and severity of treatment emergent adverse events (TEAEs) | The number and severity of treatment emergent adverse events (TEAEs) | Within 48 hours after the stop of the study drug |