Sedative Effect and Safety of Remimazolam Besylate in ARDS Patients

NCT05758597 | Recruiting Phase 4

• 1 other identifier: YXLL-KY-2022(105)
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The incidence and mortality of acute respiratory distress syndrome (ARDS) are high. Patients with ARDS often need mechanical ventilation. Rational use of sedation and analgesia can improve the tolerance of patients with mechanical ventilation and reduce the lung injury caused by mechanical ventilation. Currently, the main sedative drugs used in clinical practice are midazolam, propofol and dexmedetomidine, but they all have disadvantages. It is urgent to find a sedative drug that can achieve rapid and sufficient sedation, does not inhibit breathing, leads to rapid recovery after drug withdrawal and does not increase incidence of delirium. Remimazolam besylate is a newly marketed ultra-short-acting GABAa receptor agonist, which is not metabolized by liver or kidney and is easily hydrolyzed by non-specific esterase in vivo. It has rapid effect, short recovery time, continuous infusion with almost no accumulation, little influence on respiration and circulation, and can be antagonized by flumasini. Compared with the above traditional sedatives, it has obvious advantages, especially suitable for sedation in ICU patients. There are few studies on remimazolam besylate used for sedation in ICU patients. At present, there is a lack of evidence-based medical evidence for the application of remazolam besylate in ICU patients. Its efficacy and safety, potential advantages and dominant population, application dose and combination of drugs still need to be further explored and clarified. The objective of this study was to investigate the sedative effects and advantages of remimazolam besylate versus midazolam in patients with ARDS requiring invasive mechanical ventilation. The successful undergoing of this study will provide practical basis for clinical sedation in patients with ARDS mechanical ventilation.

Conditions

Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (6)

• Comparison of sedative effect

  Percentage of patients who achieved the target sedation range in different treatment groups

  From the date of using of remimazolam besylate Until the date of extubation, discharge from our ICU, discontinuation of study drugs for 24 hours by treating physicians, whichever came frst，assessed up to 7 days

• Comparison of respiratory status

  Oxygenation index (PaO2/FiO2) in millimeters of mercury before medication

  Before medication

• Comparison of respiratory status

  Oxygenation index (PaO2/FiO2) in millimeters of mercury 24 hours after medication

  24 hours after medication

• Comparison of respiratory status

  Oxygenation index (PaO2/FiO2) in millimeters of mercury 48 hours after medication

  48 hours after medication

• Comparison of length of stay in ICU

  length of stay in ICU between different treatment groups

  From the beginning of the study to transfer out of the ICU，assessed up to 30 days

• comparison of mortality

  mortality in different treatment groups

  From the beginning of the study to the end of follow-up, assessed up to 3 months

Study Arms (2)

Remazolam besylate group

EXPERIMENTAL

The remimazolam besylate treatment group was given remimazolam besylate 0.1-1mg/kg/h to maintain the target RASS score.

Drug: Remazolam besylate

Midazolam group

ACTIVE COMPARATOR

The midazolam treatment group was given midazolam 0.05-0.2 mg/kg/h to maintain the target RASS score.

Drug: midazolam

Interventions

Remazolam besylate DRUG

Remazolam benzoate group was given 0.1-1mg/kg/h, and the target RASS score was maintained.

Also known as: Yichang Humanwell

Remazolam besylate group

midazolam DRUG

Meanwhile the midazolam group was given 0.05-0.2 mg/kg/h midazolam, and the target RASS score was maintained.

Also known as: Jiangsu ehwa

Midazolam group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old and ≤65 years old
• ARDS patients admitted to ICU requiring invasive mechanical ventilation (meeting the 2012 Berlin diagnostic criteria for ARDS)
• Expected mechanical ventilation time \> 3 days
• Obtain informed consent from patients or family members

You may not qualify if:

• Pregnancy or lactation
• Patients with myasthenia gravis, acute myocardial ischemia or severe arrhythmia
• Severe, pre-existing substantive liver disease with clinically significant portal hypertension, Child-Pugh C cirrhosis, or acute liver failure
• Severe craniocerebral injury, brain tumor, increased intracranial pressure, cerebrovascular accident, coma, epilepsy, etc.
• Patients with a history of alcohol or drug abuse or chronic pain requiring long- term use of analgesic and sedative drugs
• Any conditions that interfere with the correct assessment of cognitive function, such as language and sensory disorders or mental disorders (language difficulties or organic mental dysfunction
• Participate in other exploratory clinical trials within 3 months prior to screening
• Known or suspected allergies to remazolam besylate, midazolam, propofol, and opioids.

Sponsors & Collaborators

• Zhiming Jiang: lead

Study Sites (1)

Department of Intensive Care Medicine

Jinan, Shandong, 250014, China

RECRUITING

Related Publications (6)

• Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, Binhas M, Genty C, Rolland C, Bosson JL. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007 Apr;106(4):687-95; quiz 891-2. doi: 10.1097/01.anes.0000264747.09017.da.

  PMID: 17413906 BACKGROUND

• ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.

  PMID: 22797452 BACKGROUND

• Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med. 2010 Jun;36(6):926-39. doi: 10.1007/s00134-010-1877-6. Epub 2010 Apr 8.

  PMID: 20376429 BACKGROUND

• Shehabi Y, Ruettimann U, Adamson H, Innes R, Ickeringill M. Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med. 2004 Dec;30(12):2188-96. doi: 10.1007/s00134-004-2417-z. Epub 2004 Aug 26.

  PMID: 15338124 BACKGROUND

• Zhang Z, Chen K, Ni H, Zhang X, Fan H. Sedation of mechanically ventilated adults in intensive care unit: a network meta-analysis. Sci Rep. 2017 Mar 21;7:44979. doi: 10.1038/srep44979.

  PMID: 28322337 BACKGROUND

• Goudra BG, Singh PM. Remimazolam: The future of its sedative potential. Saudi J Anaesth. 2014 Jul;8(3):388-91. doi: 10.4103/1658-354X.136627.

  PMID: 25191193 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Midazolam

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Zhiming Jiang, doctor

  Department of Intensive Care Medicine, Qianfoshan Hospital, Shandong Province

  STUDY DIRECTOR

Central Study Contacts

Quanzhen Wang, doctor

CONTACT

0086-15562570205; wangquanzhen1986@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Critical Care Medicine, Qianfoshan Hospital of Shandong Province

Study Record Dates

• First Submitted: November 25, 2022
• First Posted: March 7, 2023
• Study Start: January 2, 2024
• Primary Completion: May 1, 2025
• Study Completion: June 16, 2025
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)