Clinical trial NCT05555667: Long-term Sedation With Remimazolam Besylate in Critically Ill Patients
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Light Sedation
Mechanical Ventilation
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2022-09-27
Enrollment: 728
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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;

Primary outcomes:
measure: The percentage of time in the target sedation range without rescue sedation
timeFrame: 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are scheduled for surgery, are discontinued from the study drug for at least 12 hours, are discharged from ICU, or are withdrawn from the trial, whichever comes first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 outcomes:
measure: Invasive ventilator free time
timeFrame: From start of study to 7 days
measure: Successful extubation rate
timeFrame: From start of study to 7 days
measure: Length of ICU stay
timeFrame: From start of study to 28 days
measure: Mortality
timeFrame: From start of study to 28 days
measure: Length of hospitalization
timeFrame: From start of study to 28 days
measure: weaning time
timeFrame: From start of study to 7 days
measure: Rate of hypotension
timeFrame: 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
measure: Rate of hypertension
timeFrame: 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
measure: Rate of bradycardia
timeFrame: 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
measure: Rate of tachycardia
timeFrame: 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
measure: Rate of unplanned extubation of endotracheal tube
timeFrame: 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
measure: Rate of shock
timeFrame: 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
measure: Rate of hospital-acquired pneumonia
timeFrame: 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
measure: Rate of myocardial infarction
timeFrame: 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
measure: Rate of cerebral ischemic stroke
timeFrame: 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
measure: Rate of cerebral hemorrhagic stroke
timeFrame: 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
measure: Rate of pulmonary embolism
timeFrame: 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
measure: Rate of upper digestive tract ulcer confirmed endoscopically
timeFrame: 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
measure: Rate of more than 500 milliliters of bloody stool
timeFrame: 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
measure: Rate of delirium
timeFrame: 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
measure: delta SOFA
timeFrame: 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
measure: Rate of withdraw from the trial because of intolerance, severe adverse events or other safety concerns
timeFrame: 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
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study officials:
References: