Clinical Study of Esketamine in Patients With Sepsis Undergoing Invasive Mechanical Ventilation

NCT07556172 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: IIT-I-2025-061
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a syndrome of acute organ dysfunction resulting from dysregulated host responses to infection, often leading to severe complications such as acute lung injury and ARDS. ICU patients on mechanical ventilation face multiple noxious stimuli and require effective analgesic and sedative treatments to improve prognosis. The limitations of existing analgesic and sedative drugs are as follows:Opioids (such as remifentanil) have strong analgesic effects but can easily cause adverse reactions such as respiratory depression, hypotension, and gastrointestinal dysfunction.Sedative drugs like midazolam may lead to delirium and gastrointestinal dysfunction.Esketamine exerts its analgesic and sedative effects by non-competitively inhibiting the N-methyl-D-aspartate (NMDA) receptor. It has sympathomimetic activity, which can reduce hemodynamic fluctuations. It also has immunomodulatory effects, which may improve the prognosis of sepsis patients. Currently, esketamine is only used for anesthesia induction in surgery, postoperative analgesia, painless procedures, and as an adjunctive treatment for depression, with limited sample sizes and few reports. There are no large-scale clinical studies on the use of esketamine in sepsis patients undergoing invasive mechanical ventilation, and further verification of its efficacy and safety is needed.

Conditions

Sepsis; Mechanical Ventilation

Outcome Measures

Primary Outcomes (1)

• Duration of mechanical ventilation

  Duration of mechanical ventilation is defined as the cumulative length of time (in hours or days) from the initiation of invasive mechanical ventilation to the first successful liberation from the ventilator for ≥48 consecutive hours, or to death, whichever occurs first

  From intubation to the first successful extubation sustained for ≥48 hours, death, or Day 28, whichever occurs first

Secondary Outcomes (1)

• 28-Day Mortality

  From randomization to Day 28 or death, whichever occurs first

Study Arms (2)

Test group

EXPERIMENTAL

Both groups of patients received intravenous target-controlled infusion of midazolam (5mg/1ml per vial, Jiangsu Hengrui Medicine) for sedation, with a loading dose of 0.05mg/kg administered intravenously over 2 minutes, and a maintenance dose of 0.03-0.2mg/kg·h. The sedation target was a RASS score of -2 to 0. The RASS score was assessed every 4 hours, and the midazolam dose was adjusted based on the score.Experimental group: Esketamine (50mg/2ml per vial, Jiangsu Hengrui Medicine) was administered intravenously at a dose of 0.15-0.5mg/kg·h for analgesia. The analgesic target was a COPT (Composite Pain Scale) score of less than 3 points, and the dose of esketamine was adjusted according to the COPT score.

Drug: Esketamine

Control group

ACTIVE COMPARATOR

Control group: Remifentanil (1mg per vial, Yichang Humanwell Pharmaceutical) was administered intravenously at a dose of 0.05-2ug/kg·min for analgesia. The analgesic target was also a COPT score of less than 3 points, and the dose of remifentanil was adjusted based on the COPT score.

Drug: Remifentanil

Interventions

Esketamine DRUG

patients received intravenous target-controlled infusion of midazolam (5mg/1ml per vial, Jiangsu Hengrui Medicine) for sedation, with a loading dose of 0.05mg/kg administered intravenously over 2 minutes, and a maintenance dose of 0.03-0.2mg/kg·h. The sedation target was a RASS score of -2 to 0. The RASS score was assessed every 4 hours, and the midazolam dose was adjusted based on the score.Esketamine (50mg/2ml per vial, Jiangsu Hengrui Medicine) was administered intravenously at a dose of 0.15-0.5mg/kg·h for analgesia. The analgesic target was a COPT (Composite Pain Scale) score of less than 3 points, and the dose of esketamine was adjusted according to the COPT score.

Also known as: 50mg/2ml per vial, Jiangsu Hengrui Medicine

Test group

Remifentanil DRUG

patients received intravenous target-controlled infusion of midazolam (5mg/1ml per vial, Jiangsu Hengrui Medicine) for sedation, with a loading dose of 0.05mg/kg administered intravenously over 2 minutes, and a maintenance dose of 0.03-0.2mg/kg·h. The sedation target was a RASS score of -2 to 0. The RASS score was assessed every 4 hours, and the midazolam dose was adjusted based on the score.Remifentanil (1mg per vial, Yichang Humanwell Pharmaceutical) was administered intravenously at a dose of 0.05-2ug/kg·min for analgesia. The analgesic target was also a COPT score of less than 3 points, and the dose of remifentanil was adjusted based on the COPT score.

Also known as: 1mg per vial, Yichang Humanwell Pharmaceutical

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet Sepsis-3.0 diagnostic criteria.
• Age ≥ 18 years.
• Required invasive mechanical ventilation.
• Expected ICU stay ≥ 24 h.

You may not qualify if:

• Pregnant or lactating women.
• Pregnant or lactating women.
• Child-Pugh class C or worse.
• Severe renal impairment (Scr \> 178 µmol/L or BUN \> 9 mmol/L).
• Pre-existing delirium, dementia, or other psychiatric disorder.
• Known allergy to opioids or benzodiazepines.
• Uncontrolled hypertension (SBP \> 180 mmHg or DBP \> 100 mmHg).
• Preeclampsia/eclampsia.
• Significant ischemic heart disease.
• Severe pulmonary dysfunction.

Sponsors & Collaborators

• Second Affiliated Hospital of Nanchang University: lead

Study Sites (1)

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

Location

MeSH Terms

Conditions

Sepsis

Interventions

Esketamine; Remifentanil

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The experimental group was given escloracetam and midazolam for sedation and analgesia, while the control group was given remifentanil and midazolam for analgesia and sedation.

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: April 29, 2026
• Study Start: January 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)