Step 1 of A Two-step Trial to Evaluate the Effectiveness and Safety of Remimazolam Besylate for Sedation in ICU Patients

A Multicenter, Randomized, Single-blinded, Parallel, Two-step Trial to Evaluate the Effectiveness and Safety of Remimazolam Besylate for Injection for Sedation in ICU Patients

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.

Study Overview

• Status: Completed
• Conditions: Mechanically Ventilated Patients
• Intervention / Treatment: Drug: Remimazolam besylate; Drug: Remimazolam besylate; Drug: Remimazolam besylate

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	peak plasma concentration	Within 24 hours while receiving the study drug
The area under the plasma drug concentration-time curve	The area under the plasma drug concentration-time curve (AUC)	Within 24 hours while receiving the study drug
t1/2	half-life	Within 24 hours while receiving the study drug

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Collaborators: Yichang Humanwell Pharmaceutical Co., Ltd., China

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2022
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: September 29, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: WHUICU202205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No