Clinical trial NCT05160987: Effect of Remimazolam With Protocolized Sedation on Critical Ill, Mechanical Ventilated Patients Compared With Midazolam
Official title: Effect of Remimazolam With Protocolized Sedation on Critical Ill, Mechanical Ventilated Patients Compared With Midazolam - A Parallel, Multicenter, Single-blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sedation and Analgesia
Keywords: Remimazolam
Midazolam
duration of mechanical ventilation
Sedation
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
Collaborators: name: Integrated traditional Chinese and Western Medicine Hospital of Southern Medical University
name: First Affiliated Hospital of Shantou University Medical College
name: Affiliated Hospital of Guangdong Medical University
name: Yunfu People's Hospital
name: Zhongshan Hospital Of Traditional Chinese Medicine
name: Guangdong Province Traditional Medical hospital
name: The Third Affiliated Hospital of Guangzhou Medical University
First posted: 2021-12-16
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants in remimazolam group receive intravenous remimazolam. The participants in midazolam group receive midazolam.
Primary purpose: TREATMENT

Brief summary: In this parallel, multicenter, single-blind randomized controlled trial, mechanical ventilated patients will be randomly assigned to two groups. One receives remimazolam to achieve sedation goals, while the other receives Midazolam. The primary outcome is the effect of remimazolam on duration of mechanical ventilated of critical patients compared to midazolam.

Detailed description: Investigational drug#remimazolam for injection Study title#Effect of Remimazolam with Protocolized Sedation on Critical Ill, Mechanical Ventilated Patients Compared with Midazolam - A parallel, Multicenter, Single-blind Randomized Controlled Trial Principal Investigator#Professor Zhanguo Liu, Dr.Jing Cai, Department of Critical Care Unit, Zhujiang Hospital, Southern Medical University Study subjects#Critical ill patients that are mechanically ventilated within the first 48h of admission to the ICU and who would remain in the ICU for over 72h are enrolled in this study. The ages of patients should be in the range from 18 to 80.

Study phase# Investigator Initiated Trial(IIT) Study objectives#The objective of the study is to determine whether remimazolam, compared with midazolam, reduces duration of ventilation in severe patients.

Study design#A parallel, Multicenter, Single-blind Randomized Controlled Trial. Medication method#Remimazolam group#Patients are administered with a bolus of remimazolam with 0.1-0.3mg/kg intravenously in 1 minute for the first time. And the maintenance dose is 0.25-0.1mg/kg/h, meanwhile the dose of remimazolam should be titrated according to Richmond Agitation Sedation Scale (RASS) scores. Nonbenzodiazepines could be administrated to the patients if sedation targets were not achieved.

Midazolam group#Patients are administered with a bolus of midazolam with 0.01-0.05mg/kg intravenously in 1 minute for the first time. And maintenance dose is 0.02-0.1mg/kg/h, meanwhile the dose of midazolam should be titrated according to Richmond Agitation Sedation Scale (RASS) scores. Nonbenzodiazepines could be administrated to the patients if sedation targets were not achieved.

Spontaneous breathing test (SBT) is conducted daily while patients are stable. Weaning would be considered after a successful SBT, and the sedation for study need to be stopped subsequently. If the weaning failed, mechanical ventilation and sedation would be used immediately according to sedation targets. Weaning success is defined as the ability to successfully complete the SBT and sustain spontaneous breathing for 48h after extubation.

Course#28days Sample size#440. Sites#15 Primary endpoint#Duration of mechanical ventilation(weaning success is typically regarded as consecutive ventilator-free over 24h following liberation from a ventilator. The duration of mechanical ventilation is from the enrollment time to the weaning time. The study and observation would be stopped due to difficult ventilator weaning, which features weaning failure repeatedly for 3 weeks.) Secondary endpoints#

1. Duration of endotracheal intubation(calculated from the time of enrollment);
2. Completion rate of sedation goals (completion rate of sedation goal = days of achieving sedation goals / total days of sedation (days from enrollment to successful ventilator withdrawal) × 100%）)；
3. Sedation remediation is defined as requiring combination with other nonbenzodiazepines sedations.
4. Length of stay in ICU and total length of stay (time from admission to discharge);
5. Others: anterograde amnesia, 28 day mortality, total cost of sedative drugs in ICU, hospitalization expenses in ICU; Anterograde amnesia used a questionnaire that is record to assess the patient's forgetfulness.

Safety endpoints#

1. Incidence of Hypotension(20% fall in systolic pressure).
2. Incidence of Delirium.
3. Incidence of spontaneous extubation.
4. Incidence of reintubation in 12h or tracheotomy.
5. Incidence of Myasthenia.(following weaning from ventilations)
6. Incidence of thrombus.(lower extremity deep venous thrombosis)

Eligibility criteria: Inclusion Criteria:

1. Critical ill patients that are mechanically ventilated within the first 48h of admission to the ICU and who would remain in the ICU for over 72h were enrolled in this study.
2. Age 18-80 years.
3. Voluntary informed consent.

Exclusion Criteria:

1. Surgical treatment is performed within 24 hours.
2. Craniocerebral injury, post neurosurgery, non drug coma, mental illness or peripheral neuropathy.
3. Heart rates are less than 50 beats / min or severe atrioventricular block without pacemaker support.
4. The mean arterial pressure is less than 55 mmHg even though fluids and vasoactive drugs are administrated.
5. Patients who are known or suspected allergy to benzodiazepines, propofol, dexmedetomidine or opioids.
6. History of alcohol and drug abuse.
7. End stages of lung diseases, such as pulmonary fibrosis, lung damage, etc.
8. Pregnancy.

Primary outcomes:
measure: Duration of mechanical ventilation
timeFrame: From the date of enrollment until the date of successful ventilator withdrawal, assessed up to 28 days
Secondary outcomes:
measure: Duration of endotracheal intubation
timeFrame: From the date of enrollment until the date of pulling out the endotracheal tube, assessed up to 28 days
measure: Completion rate of sedation goal
timeFrame: From the date of enrollment until the date of successful ventilator withdrawal, assessed up to 28 days
measure: Remediation is defined as requiring combination with other sedations
timeFrame: From the date of enrollment until the date of successful ventilator withdrawal, assessed up to 28 days
measure: Length of stay in ICU and total length of stay
timeFrame: From the date of admission in ICU until the date of transfer from ICU
measure: Anterograde amnesia
timeFrame: From the date of enrollment until the date of successful ventilator withdrawal
measure: 28 day mortality
timeFrame: From the date of enrollment until the date of death from any cause, assessed up to 28 days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University
state: Guangdong
Study officials:
affiliation: Department of Critical Care Medicine of Zhujiang Hospital
name: Zhanguo Liu, M.D.PhD
role: PRINCIPAL_INVESTIGATOR
References: