Effect of Remimazolam With Protocolized Sedation on Critical Ill, Mechanical Ventilated Patients Compared With Midazolam

Effect of Remimazolam With Protocolized Sedation on Critical Ill, Mechanical Ventilated Patients Compared With Midazolam - A Parallel, Multicenter, Single-blind Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Sedation and Analgesia
• Intervention / Treatment: Drug: Remimazolam; Drug: 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)

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jing Cai; Phone Number: +86-2062782927; Email: caijing78@hotmail.com
• Study Contact Backup: Name: Zhanguo Liu, M.D.PhD; Phone Number: +86-2062782927; Email: zhanguoliu@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510282
      • Recruiting
      • Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University
      • Contact: Ping Chang, M.D.PhD; Phone Number: +86-2062782927; Email: changp963@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam Group; The patients are administered with sedation of remimazolam and analgesia of remifentanil on the basis of routine treatment. If the patient does not receive sedative drug before enrollment, patient would be administered with a bolus of remimazolam with 0.1-0.3mg/kg intravenously in 1 minute for the first time. And maintenance dose is 0.25-0.1mg/kg/h, meanwhile the dose of remimazolam should be titrated according to RASS scores. Nonbenzodiazepines could be administrated to the patients if sedation targets were not achieved, and the medication and dosage is recorded.	Drug: Remimazolam; Remimazolam will be diluted with 0.9% saline to ensure that the therapeutic drug and placebo are identical in appearance, and 50 ml syringes will serve as the containers for all intravenous drugs.
Placebo Comparator: Midazolam Group; The patients are administered with sedation of midazolam analgesia of remifentanil on the basis of routine treatment. If the patient does not receive sedative drugs before enrollment, patients would be administered with a bolus of midazolam with 0.01-0.05mg/kg intravenously in 1 minute for the first time. And the maintenance dose is 0.02-0.1mg/kg/h, meanwhile the dose of midazolam should be titrated according to RASS scores. Nonbenzodiazepines could be administrated to the patients if sedation targets were not achieved, and the medication and dosage is recorded.	Drug: Midazolam; Midazolam will be diluted with 0.9% saline to ensure that the therapeutic drug and placebo are identical in appearance, and 50 ml syringes will serve as the containers for all intravenous drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From the date of enrollment until the date of successful ventilator withdrawal, assessed up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of endotracheal intubation	Duration of endotracheal intubation	From the date of enrollment until the date of pulling out the endotracheal tube, assessed up to 28 days
Completion rate of sedation goal	completion rate of sedation goal = days of achieving sedation goals / total days of sedation (days from enrollment to successful ventilator withdrawal) × 100%	From the date of enrollment until the date of successful ventilator withdrawal, assessed up to 28 days
Remediation is defined as requiring combination with other sedations	If the sedation goal cannot be reached, the clinician will use non benzodiazepines according to the actual situation of the patient, and record the medication and dosage.	From the date of enrollment until the date of successful ventilator withdrawal, assessed up to 28 days
Length of stay in ICU and total length of stay	Length of stay in ICU and total length of stay	From the date of admission in ICU until the date of transfer from ICU
Anterograde amnesia	Anterograde amnesia used a questionnaire to record their memories of related events during mechanical ventilation (turning over, sputum suction, vascular catheterization, nocturnal nursing medication and other invasive operations). Assess the patient's forgetfulness.	From the date of enrollment until the date of successful ventilator withdrawal
28 day mortality	28 day mortality	From the date of enrollment until the date of death from any cause, assessed up to 28 days

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Collaborators: The Third Affiliated Hospital of Guangzhou Medical University; First Affiliated Hospital of Shantou University Medical College; Zhongshan Hospital Of Traditional Chinese Medicine; Integrated traditional Chinese and Western Medicine Hospital of Southern Medical University; Yunfu People's Hospital; Guangdong Province Traditional Medical hospital; Affiliated Hospital of Guangdong Medical University
• Investigators: Principal Investigator: Zhanguo Liu, M.D.PhD, Department of Critical Care Medicine of Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: November 29, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Sedation; Midazolam; Remimazolam; duration of mechanical ventilation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 2021-KY-089-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Since some data may involve patients privacy. We have no plans to share data so far, and some data may be shared later depending on the patient's wishes.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No