Long-term Sedation With Remimazolam Besylate in Critically Ill Patients

Phase 3

Recruiting

• Conditions: Light Sedation; Mechanical Ventilation
• Interventions: Drug: Remimazolam besylate; Drug: Propofol

• Registration Number: NCT05555667
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

A randomized non-inferior trial comparing remimazolam besylate with propofol for long-term sedation during invasive mechanical ventilation in critically ill patients

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-09
• Study First Submitted: 2022-09-22
• Study First Submitted QC: 2022-09-26
• Study First Posted: 2022-09-27
• Study Start: 2023-05-16
• Last Update Submitted: 2023-05-24
• Last Update Posted: 2023-05-26
• Primary Completion: 2025-11-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 728

Inclusion Criteria

• Age ≥ 18 and ≤ 80 years;
• Intubated and mechanically ventilated ≤96 hours before enrollment；
• Expected to require continuous invasive ventilation and sedation ≥24 hours;
• Requirement for light to moderate sedation (a RASS score of -3 to 0)

Exclusion Criteria

• Body mass index (BMI) <18 or >30 kg/m2;
• Allergy or unsuitabilty to any composition of study drugs or remifentanil;
• Living expectancy less than 48 hours；
• Possible surgey in the operating room in 24 hours；
• Myasthenia gravis;
• Serious hepatic dysfunction (CTP 10-15);
• Chronic kidney disease with glomerular filtration rate (GFR) < 29 ml/min/1.73m2;
• Systolic blood pressure less than 90 mm Hg after appropriate intravenous volume replacement and continuous infusions of 2 vasopressors;
• Acute severe neurological disorder and any other condition interfering with RASS assessment;
• Pregnancy or lactation;
• Unstable angina or acute myocardial infarction;
• Left ventricular ejection fraction less than 30%;
• Heart rate less than 50 beats/min;
• Grade 2 , second degree or third degree atrioventricular block in the absence of a pacemaker;
• Abuse of controlled substances or alcohol;
• Other conditions deemed unsuitable to be included;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Remimazolam besylate	Remimazolam besylate	Remimazolam besylate at an initial infusion rate of 0.15 mg/kg/h and adjusted (maximum of 0.3 mg/kg/h) to maintain a RASS score between - 3 and 0
Propofol	Propofol	Propofol intravenously at an initial infusion rate of 2.0 mg/kg/h and adjusted (maximum of 4.0 mg/kg/h) to maintain a RASS score between - 3 and 0

Primary Outcome Measures

Name	Time	Method
The percentage of time in the target sedation range without rescue sedation	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	The percentage of time in the target sedation range without rescue sedation

Secondary Outcome Measures

Name	Time	Method
Invasive ventilator free time	From start of study to 7 days	Hours of time free from invasive ventilator
Length of ICU stay	From start of study to 28 days	Length of ICU stay
weaning time	From start of study to 7 days	weaning time in minutes between continuous discontinuation of the study drug and extubation in patients with successful extubation
Rate of hypertension	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mmHg for 5 minutes or treated with vasodilators
Rate of shock	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	New-onset shock
Rate of cerebral ischemic stroke	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	cerebral ischemic stroke
Rate of upper digestive tract ulcer confirmed endoscopically	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	upper digestive tract ulcer confirmed endoscopically
Rate of more than 500 milliliters of bloody stool	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	more than 500 milliliters of bloody stool
Rate of hypotension	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	Systolic blood pressure less than 80 mmHg or diastolic blood pressure less than 50 mmHg for 5 minutes or treated with vasopressors
Rate of bradycardia	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	heart rate less than 50 bpm for 5 minutes or treated with medication to increase heart rate
Rate of tachycardia	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	heart rate greater than 120 bpm for 5 minutes or treated with medication to decrease heart rate
Rate of hospital-acquired pneumonia	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	hospital-acquired pneumonia
delta SOFA	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	defined as the difference between SOFA when each patient stops receiving the study drug and SOFA at inclusion
Rate of unplanned extubation of endotracheal tube	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	unplanned extubation of endotracheal tube
Rate of delirium	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	delirium
Successful extubation rate	From start of study to 7 days	Extubation of endotracheal tube for the first time in 7 days without reintubation or switching to tracheostomy within the following 48 hours
Mortality	From start of study to 28 days	Mortality
Length of hospitalization	From start of study to 28 days	Length of hospitalization
Rate of withdraw from the trial because of intolerance, severe adverse events or other safety concerns	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	rate of withdraw from the trial because of intolerance, severe adverse events or other safety concerns
Rate of myocardial infarction	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	myocardial infarction
Rate of cerebral hemorrhagic stroke	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	Rate of cerebral hemorrhagic stroke
Rate of pulmonary embolism	7 days after enrollment, or when patients decease, require deep sedation, are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first	pulmonary embolism

Trial Locations

Locations (1)

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, China