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

April 21, 2026 updated by: Second Affiliated Hospital of Nanchang University

A Clinical Study of Esketamine for Sedation, Delirium Prevention and Clinical Outcomes in Septic Patients Under Invasive Mechanical Ventilation

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Sepsis is circulatory dysfunction or failure caused by infection. When a pathogen infects the body, the body activates autoimmune mechanisms to eliminate the pathogen. While removing pathogens, it often causes damage to its own capillary endothelium, capillary leakage, coagulation dysfunction, and local inflammatory damage. Acute lung injury is characterized by refractory hypoxemia and respiratory distress, which can further develop into more severe acute respiratory distress syndrome; Patients with pulmonary inflammation characterized by decreased lung compliance and ventilation/flow dysbivie requiring invasive mechanical ventilation to improve oxygen uptake are common in the ICU.ICU mechanically ventilated patients are in a strong stress environment, and invasive mechanically ventilated patients must experience a variety of nociceptive stimuli of different intensities in the process of receiving treatment, such as antiphysiological ventilation mode, restraint and immobilization, tracheal tube stimulation, various puncture operations, wound care, sputum suction, and environmental factors stimuli, etc., on the basis of the influence of the primary disease, these exogenous stimuli can cause strong discomfort in patients and induce severe physical and psychological stress, which is to cause patients to have anxiety, restlessness, Delirium and other important causes of adverse events (1) can even have an adverse effect on clinical prognosis. For patients with respiratory failure and strong compensatory drive for spontaneous breathing, an appropriate depth of analgesia and sedation is required to minimize the patient's excessive spontaneous respiratory drive and reduce stretch damage to lung tissue. Effective analgesia and sedation can reduce the metabolic rate of patients, reduce their oxygen consumption demand, make the changes in oxygen consumption demand of body tissues adapt to the damaged oxygen delivery state as much as possible, and reduce the metabolic burden of various organs, thereby reducing the damage caused by strong pathological factors and creating conditions for the recovery of organ function. Therefore, it is the basic task of critical care to effectively control the disease factors and various injury stimuli caused by intensive medical measures through appropriate analgesia and sedation treatment, and to maintain the comfort and safety of patients with invasive mechanical ventilation.Opioids are one of the powerful central analgesics, which have the advantages of strong analgesic effect, fast onset, strong adjustability, and low price, and are the basic drugs in the pain management of ICU patients. However, the adverse effects of opioids are mainly caused by respiratory depression, a drop in blood pressure, and a decrease in gastrointestinal motility, especially in the elderly. Thus, the use of opioids in patients with sepsis may affect their hemodynamic and gastrointestinal function.The ideal sedative, analgesic or combination regimen requires not only adequate sedation and analgesia, but also rapid onset of action, rapid awakening after discontinuation of the drug, minimal accumulation in the body and minimal circulatory impact, and anti-anxiety and anti-delirium effects. Ketamine is a commonly used anesthetic drug with good sedative and analgesic effects. However, due to the adverse reactions of the drug such as postoperative nightmares and extrapyramidal syndrome, the clinical application of the drug in the late 90s of the 20th century has decreased. Esketamine is a pure dextrarive enantiomer of ketamine, which can be used for analgesia and anesthesia in clinical practice, mainly through non-competitive inhibition of N-methyl-D-aspartate receptors to exert analgesic and sedative effects. The analgesic, sedative, and anesthetic effects of esketamine are dose-dependent, and the anesthesia has a rapid onset and relatively short duration, and its combination with benzodiazepines can greatly reduce the risk of psychotic reactions during awakening. For hemodynamically unstable mechanically ventilated patients, the use of analgesic and sedative drugs often further affects hemodynamic stability, but esketamine can inhibit the reuptake of norepinephrine by sympathetic nerve endings in the body, cause adrenergic hyperactivity, increase the concentration of norepinephrine in the circulatory system, and produce sympathomimetic activity, which can effectively reduce this adverse reaction. Moreover, esketamine does not produce respiratory drive inhibition, and patients can resume spontaneous breathing relatively early, accelerating the weaning process. In addition, esketamine has immunomodulatory effects, which can reduce the level of inflammatory factors and improve the prognosis of patients with sepsis. Therefore, esketamine in patients with sepsis who are invasively mechanically ventilated may have certain advantages in improving hemodynamics and reducing respiratory depression and gastrointestinal adverse effects.Esketamine is currently only used as an adjunct to anesthesia induction during surgery, postoperative analgesia and painless procedures, and depression, with a small sample size and few reports. There are no similar reports on its use in sepsis, so its efficacy and safety need to be further validated in randomized prospective clinical studies.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangxi
      • Nanchang, Jiangxi, China, 330000
        • The Second Affiliated Hospital of Nanchang University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Test group
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
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.
Other Names:
  • 50mg/2ml per vial, Jiangsu Hengrui Medicine
Active Comparator: Control group
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
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.
Other Names:
  • 1mg per vial, Yichang Humanwell Pharmaceutical

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Duration of mechanical ventilation
Time Frame: From intubation to the first successful extubation sustained for ≥48 hours, death, or Day 28, whichever occurs first
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
28-Day Mortality
Time Frame: From randomization to Day 28 or death, whichever occurs first
28-day mortality is defined as the proportion of patients who die from any cause within 28 days following randomization, expressed as a percentage of the total randomized study population
From randomization to Day 28 or death, whichever occurs first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Affiliated Hospital of Nanchang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 11, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 29, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IIT-I-2025-061

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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