Long-term Sedation With Remimazolam Besylate in Critically Ill Patients

Mechanical Ventilation Clinical Trial

— LOSREB  

Official title:

Long-term Sedation With Remimazolam Besylate Versus Propofol in Critically Ill Patients During Invasive Mechanical Ventilation: a Randomized Non-inferior Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05555667
• Other study ID #: WHUICU202209
• Status: Recruiting
• Phase: Phase 3
• Start date: May 16, 2023
• Est. completion date: December 1, 2025

Study information

• Verified date: September 2022
• Source: Wuhan Union Hospital, China
• Contact: You Shang, MD
• Phone: 008602785726114
• Email: you_shanghust[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 728
• Est. completion date: December 1, 2025
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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;

Related Conditions & MeSH terms

• Critical Illness
• Mechanical Ventilation

Intervention

Drug:
• Remimazolam besylate
Sedation drug
• Propofol
Propofol. Sedation drug

Locations

Country	Name	City	State
China	Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of time in the target sedation range without rescue sedation	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
Secondary	Invasive ventilator free time	Hours of time free from invasive ventilator	From start of study to 7 days
Secondary	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	From start of study to 7 days
Secondary	Length of ICU stay	Length of ICU stay	From start of study to 28 days
Secondary	Mortality	Mortality	From start of study to 28 days
Secondary	Length of hospitalization	Length of hospitalization	From start of study to 28 days
Secondary	weaning time	weaning time in minutes between continuous discontinuation of the study drug and extubation in patients with successful extubation	From start of study to 7 days
Secondary	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	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	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	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	Rate of bradycardia	heart rate less than 50 bpm for 5 minutes or treated with medication to increase heart rate	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	Rate of tachycardia	heart rate greater than 120 bpm for 5 minutes or treated with medication to decrease heart rate	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	Rate of unplanned extubation of endotracheal tube	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
Secondary	Rate of shock	New-onset 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
Secondary	Rate of hospital-acquired pneumonia	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
Secondary	Rate of myocardial infarction	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
Secondary	Rate of cerebral ischemic stroke	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
Secondary	Rate of cerebral hemorrhagic stroke	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
Secondary	Rate of pulmonary embolism	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
Secondary	Rate of upper digestive tract ulcer confirmed endoscopically	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
Secondary	Rate of more than 500 milliliters of bloody stool	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
Secondary	Rate of delirium	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
Secondary	delta SOFA	defined as the difference between SOFA when each patient stops receiving the study drug and SOFA at inclusion	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	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	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