Back to resultsLong-term Sedation With Remimazolam Besylate in Critically Ill Patients (LOSREB)
Primary Purpose
Light Sedation, Mechanical Ventilation
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Remimazolam besylate
Propofol
Sponsored by
About this trial
This is an interventional treatment trial for Light Sedation
Eligibility Criteria
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;
Sites / Locations
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Remimazolam besylate
Propofol
Arm Description
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 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
Outcomes
Primary Outcome Measures
The percentage of time in the target sedation range without rescue sedation
The percentage of time in the target sedation range without rescue sedation
Secondary Outcome Measures
Invasive ventilator free time
Hours of time free from invasive ventilator
Successful extubation rate
Extubation of endotracheal tube for the first time in 7 days without reintubation or switching to tracheostomy within the following 48 hours
Length of ICU stay
Length of ICU stay
Mortality
Mortality
Length of hospitalization
Length of hospitalization
weaning time
weaning time in minutes between continuous discontinuation of the study drug and extubation in patients with successful extubation
Rate of hypotension
Systolic blood pressure less than 80 mmHg or diastolic blood pressure less than 50 mmHg for 5 minutes or treated with vasopressors
Rate of hypertension
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 bradycardia
heart rate less than 50 bpm for 5 minutes or treated with medication to increase heart rate
Rate of tachycardia
heart rate greater than 120 bpm for 5 minutes or treated with medication to decrease heart rate
Rate of unplanned extubation of endotracheal tube
unplanned extubation of endotracheal tube
Rate of shock
New-onset shock
Rate of hospital-acquired pneumonia
hospital-acquired pneumonia
Rate of myocardial infarction
myocardial infarction
Rate of cerebral ischemic stroke
cerebral ischemic stroke
Rate of cerebral hemorrhagic stroke
Rate of cerebral hemorrhagic stroke
Rate of pulmonary embolism
pulmonary embolism
Rate of upper digestive tract ulcer confirmed endoscopically
upper digestive tract ulcer confirmed endoscopically
Rate of more than 500 milliliters of bloody stool
more than 500 milliliters of bloody stool
Rate of delirium
delirium
delta SOFA
defined as the difference between SOFA when each patient stops receiving the study drug and SOFA at inclusion
Rate of withdraw from the trial because of intolerance, severe adverse events or other safety concerns
rate of withdraw from the trial because of intolerance, severe adverse events or other safety concerns
Full Information
NCT ID
NCT05555667
First Posted
September 22, 2022
Last Updated
May 24, 2023
Sponsor
Wuhan Union Hospital, China
1. Study Identification
Unique Protocol Identification Number
NCT05555667
Brief Title
Long-term Sedation With Remimazolam Besylate in Critically Ill Patients
Acronym
LOSREB
Official Title
Long-term Sedation With Remimazolam Besylate Versus Propofol in Critically Ill Patients During Invasive Mechanical Ventilation: a Randomized Non-inferior Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 16, 2023 (Actual)
Primary Completion Date
November 1, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wuhan Union Hospital, China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A randomized non-inferior trial comparing remimazolam besylate with propofol for long-term sedation during invasive mechanical ventilation in critically ill patients
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Light Sedation, Mechanical Ventilation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
728 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Remimazolam besylate
Arm Type
Experimental
Arm Description
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
Arm Title
Propofol
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Remimazolam besylate
Intervention Description
Sedation drug
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
Propofol. Sedation drug
Primary Outcome Measure Information:
Title
The percentage of time in the target sedation range without rescue sedation
Description
The percentage of time in the target sedation range without rescue sedation
Time Frame
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
Secondary Outcome Measure Information:
Title
Invasive ventilator free time
Description
Hours of time free from invasive ventilator
Time Frame
From start of study to 7 days
Title
Successful extubation rate
Description
Extubation of endotracheal tube for the first time in 7 days without reintubation or switching to tracheostomy within the following 48 hours
Time Frame
From start of study to 7 days
Title
Length of ICU stay
Description
Length of ICU stay
Time Frame
From start of study to 28 days
Title
Mortality
Description
Mortality
Time Frame
From start of study to 28 days
Title
Length of hospitalization
Description
Length of hospitalization
Time Frame
From start of study to 28 days
Title
weaning time
Description
weaning time in minutes between continuous discontinuation of the study drug and extubation in patients with successful extubation
Time Frame
From start of study to 7 days
Title
Rate of hypotension
Description
Systolic blood pressure less than 80 mmHg or diastolic blood pressure less than 50 mmHg for 5 minutes or treated with vasopressors
Time Frame
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
Title
Rate of hypertension
Description
systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mmHg for 5 minutes or treated with vasodilators
Time Frame
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
Title
Rate of bradycardia
Description
heart rate less than 50 bpm for 5 minutes or treated with medication to increase heart rate
Time Frame
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
Title
Rate of tachycardia
Description
heart rate greater than 120 bpm for 5 minutes or treated with medication to decrease heart rate
Time Frame
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
Title
Rate of unplanned extubation of endotracheal tube
Description
unplanned extubation of endotracheal tube
Time Frame
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
Title
Rate of shock
Description
New-onset shock
Time Frame
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
Title
Rate of hospital-acquired pneumonia
Description
hospital-acquired pneumonia
Time Frame
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
Title
Rate of myocardial infarction
Description
myocardial infarction
Time Frame
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
Title
Rate of cerebral ischemic stroke
Description
cerebral ischemic stroke
Time Frame
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
Title
Rate of cerebral hemorrhagic stroke
Description
Rate of cerebral hemorrhagic stroke
Time Frame
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
Title
Rate of pulmonary embolism
Description
pulmonary embolism
Time Frame
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
Title
Rate of upper digestive tract ulcer confirmed endoscopically
Description
upper digestive tract ulcer confirmed endoscopically
Time Frame
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
Title
Rate of more than 500 milliliters of bloody stool
Description
more than 500 milliliters of bloody stool
Time Frame
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
Title
Rate of delirium
Description
delirium
Time Frame
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
Title
delta SOFA
Description
defined as the difference between SOFA when each patient stops receiving the study drug and SOFA at inclusion
Time Frame
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
Title
Rate of withdraw from the trial because of intolerance, severe adverse events or other safety concerns
Description
rate of withdraw from the trial because of intolerance, severe adverse events or other safety concerns
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
You Shang, MD
Phone
008602785726114
Ext
61606
Email
you_shanghust@163.com
Facility Information:
Facility Name
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaobo Yang
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Long-term Sedation With Remimazolam Besylate in Critically Ill Patients
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