Effect of Remimazolam Sedation on Outcomes of Mechanically Ventilated Patients in the ICU

The goal of this clinical trial is to evaluate the effect of remimazolam sedation on outcomes of mechanically ventilated ICU patients through a single-center, prospective, randomized controlled, pilot study.

Study Overview

• Status: Recruiting
• Conditions: Sedation; Mechanically Ventilated ICU Patients; Remimazolam Besylate
• Intervention / Treatment: Drug: Remimazolam; Drug: propofol

Detailed Description

Worldwide, approximately 13-20 million patients receive mechanical ventilation in intensive care units (ICUs) each year. As a crucial life-support modality, mechanical ventilation is widely used for the management of respiratory failure due to various causes, as well as for respiratory support during anesthesia and after surgery. However, mechanical ventilation may also induce anxiety, pain, and patient-ventilator asynchrony, leading to increased oxygen consumption, a higher risk of barotrauma, and potentially worse patient outcomes. Therefore, patients undergoing mechanical ventilation usually require sedatives to improve comfort and safety, reduce anxiety, optimize ventilation efficacy, and decrease the incidence of complications.

In current clinical practice, various sedatives such as midazolam, propofol, and dexmedetomidine are widely used, all of which can effectively achieve sedation. Midazolam is a classic benzodiazepine sedative widely used in the ICU. It exerts central inhibitory effects by enhancing γ-GABA-mediated neurotransmission, thereby producing sedation, anxiolysis, and anterograde amnesia. However, it has a relatively slow onset and tends to accumulate in the body, leading to prolonged recovery time. Propofol is known for its rapid onset, short duration of action, and quick recovery after discontinuation. Its depth of sedation is positively correlated with the administered dose. Nevertheless, propofol may increase hemodynamic instability by reducing vascular tone and decreasing venous return, and it also exerts respiratory depression. Moreover, high-dose or long-term use of propofol can potentially cause fatal propofol infusion syndrome. Dexmedetomidine, a selective α2-adrenergic receptor agonist, reduces sympathetic overactivity by inhibiting norepinephrine release from the locus coeruleus and competitively binding to α2 receptors, thereby producing sedation, anxiolysis, and mild analgesia. Patients sedated with dexmedetomidine are relatively easy to arouse and have a lower incidence of respiratory depression, but this drug tends to cause hypotension and bradycardia.

Remimazolam, a novel ultra-short-acting benzodiazepine sedative, exerts its sedative effects by binding to and enhancing the activity of GABAA receptors, thereby reducing neuronal excitability. It features rapid onset, predictable sedative effect, lack of accumulation in the body, quick metabolism, mild cardiorespiratory depression, and low dependence on hepatic and renal function. The sedative effect of remimazolam can be reversed by the specific benzodiazepine antagonist flumazenil. Given these properties, remimazolam is considered an ideal sedative in the ICU and an excellent choice for sedation in critically ill patients. In recent years, it has been gradually applied in procedural sedation and general anesthesia. In a multicenter, randomized, single-blind, non-inferiority trial of mechanically ventilated ICU patients, remimazolam was found to be non-inferior to propofol in achieving short-term light sedation. In addition, a preliminary study by Tang Y and colleagues showed that remimazolam was similarly effective and safe for long-term sedation in mechanically ventilated ICU patients compared with propofol [10].

As an emerging drug, remimazolam has a relatively short history of clinical use. Current research on this drug is mainly concentrated in the fields of endoscopy and anesthesiology, with relatively few studies focusing on its sedative application in ICU patients. Therefore, the aim of this study was to evaluate the effect of ective, randomized controlled, pilot study was conducted to evaluate the effect of remimazolam sedation on outcomes of mechanically ventilated ICU patients.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jingyuan Xu, M.D.; Phone Number: 00862583262500; Email: xujingyuanmail@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Zhongda Hospital
      • Contact: Jingyuan Xu, M.D.; Phone Number: 00862583262500; Email: xujingyuanmail@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Endotracheal intubation and mechanical ventilation for 24-96 hours before enrollment Expected need for continued invasive ventilation and sedation for at least 24 hours;
• Target sedation depth on the Richmond Agitation-Sedation Scale (RASS) between 0 and -3;
• Informed consent obtained from the patient's family

Exclusion Criteria:

• Body mass index (BMI) > 30 kg/m²
• Severe central nervous system disease (e.g., acute stroke, uncontrolled seizures, or severe dementia) or any other condition that precludes RASS assessment
• Mean arterial pressure (MAP) < 55 mmHg despite intravenous fluid resuscitation and vasopressors
• Heart rate < 50 beats per minute, or second-degree or third-degree atrioventricular block in the absence of a pacemaker
• Acute myocardial infarction or severe heart failure (New York Heart Association [NYHA] class IV)
• Left ventricular ejection fraction < 30%
• Any contraindication or allergy to benzodiazepines
• Substance dependence, alcohol abuse, or psychiatric/psychological disorders. Alcohol abuse was defined as regular consumption of > 14 drinks per week (1 drink = 150 mL wine, 360 mL beer, or 45 mL liquor)
• Acute hepatitis or severe hepatic dysfunction (Child-Pugh class C)
• Chronic kidney disease with a glomerular filtration rate (GFR) < 60 mL/min/1.73 m²
• Neuromuscular disease
• Patients on extracorporeal membrane oxygenation (ECMO)
• Pregnancy or breastfeeding

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
Active Comparator: propofol	Drug: propofol; In the control group, patients received propofol emulsion injection at a loading dose of 0.3 mg/kg/h injected over 1 min, followed by a continuous infusion at a rate of 0.3 mg/kg/h. Dose adjustments were made in increments of 0.3-0.6 mg/kg/h, within a dose range of 0.3-4 mg/kg/h, to achieve the target sedation level (RASS: -3 to 0).
Experimental: remimazolam	Drug: Remimazolam; In the intervention group, patients with a Richmond Agitation-Sedation Scale (RASS) score of -3 to 0 were given remimazolam besylate for injection at a loading dose of 0.08 mg/kg infused intravenously over 10 min, followed by a continuous infusion at a rate of 0.2 mg/kg/h. When dose adjustment was required, each step was 0.1-0.2 mg/kg/h, with a dose range of 0-2 mg/kg/h, until the target sedation level (RASS: -3 to 0) was achieved. If the target sedation level was not reached, an additional bolus dose of 0.08 mg/kg remimazolam besylate could be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
28-day ventilator-free days	28-day

Secondary Outcome Measures

Outcome Measure	Time Frame
28-day mortality	28-day
Incidence of delirium	Up to 28 days
28-day shock-free days	28-day
ICU length of stay	Up to 30 days
hospital length of stay	Up to 60 days

Collaborators and Investigators

• Sponsor: Southeast University, China

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ICU; sedation; remimazolam
• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Propofol; remimazolam
• Other Study ID Numbers: 2022ZDSYLL327-P01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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