Adjunctive Esketamine for Analgesia in Mechanically Ventilated Septic Shock Patients

November 20, 2023 updated by: Nanfang Hospital, Southern Medical University

Adjunctive Esketamine for Analgesia in Mechanically Ventilated ICU Septic Shock Patients

Sedation and analgesia in patients with sepsis and hemodynamic instability may be challenging in the ICU. Opioids and propofol can further exacerbate tissue infusion in septic shock by reducing cardiac contractility, increasing vasodilation, and reducing respiratory drive. Ketamine is an NMDA receptor antagonist, which has no effect on respiratory drive and has diastolic airway smooth muscle and anti-inflammatory properties. Esketamine is a dextrorotatory cleavage twice as potent and reduces the incidence of dose-dependent side effects of ketamine. Although it has been successfully used in burn patients undergoing multiple operations and anesthesia-related maintenance analgesia, it has not been reported in ICU septic shock patients undergoing mechanical ventilation. The purpose of this study was to explore the use of esketamine in mechanically ventilated ICU septic shock patients in a single-center randomized controlled trial.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
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

In order to further clarify whether Esketamine can be used as a conventional continuous intravenous infusion drug in the ICU, further RCT is required. Therefore, this project assumes that low-dose Esketamine has a clear analgesic and sedative effect, and has advantages such as less adverse reactions in hemodynamics, respiratory inhibition, and gastrointestinal peristalsis. It is proposed to complete the following work: on the standard analgesia and sedation scheme (remifentanil+propofol), evaluate the feasibility, effectiveness and safety of the auxiliary analgesia scheme added with esketamine for septic shock patients with mechanical ventilation by whether to load small dose of esketamine for infusion, so as to provide basis for follow-up individualized diagnosis and treatment.

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.
124

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 3

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
      • Guangzhou, China, 510515
        • Recruiting
        • Southern Medical University Nanfang Hospital
        • Contact:

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:

  • Age ≥ 18;
  • A patient diagnosed with septic shock;
  • It needs to be treated with analgesics, sedatives, and vasopressors for a period of not less than 48 hours;
  • Mechanical ventilation by the ventilator is needed;
  • Obtain the informed consent of the human subjects or their legal representatives;

Exclusion Criteria:

  • Currently pregnant or breastfeeding;
  • Confirmed acute severe intracranial or spinal neurologic diseases caused by vascular, intracranial expansion, or injury;
  • History of uncontrolled or malignant hypertension (sustained (>3 hours) heart rate >150 beats/min or systolic blood pressure >180 mmHg); recent history of ketamine use；
  • Hearing or vision loss, or any other conditions likely to severely interfere with the collection of research data;
  • Long-term use of benzodiazepines or opioids;
  • Known allergy to any investigational drug;
  • Subject receiving sedative therapy not for tolerance to mechanical ventilation (e.g., seizures);
  • Unlikely to require ongoing sedation during mechanical ventilation (e.g., Guillain-Barré syndrome);
  • Patients deemed unlikely by the attending physician to be weaned from mechanical ventilation, such as those with diseases/injuries primarily affecting respiratory neuromuscular function and conditions requiring prolonged ventilatory support, which are clearly irreversible (e.g., high spinal cord injury);
  • Open eye injury or other ophthalmic diseases;
  • Concurrent participation in any other interventional study (any study assigning subjects to different treatment groups and/or conducting unconventional diagnostic or monitoring procedures).

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: Single

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.
Active Comparator: Remifentanil + propofol + esketamine
esketamine (2ml; 50mg), Remifentanil Hydrochloride for Injection (1mg;), propofol injection (50ml; 0.5g; )； The frequency of use is determined by responsible clinicians.All analgesic and sedative drugs used are adjusted according to the actual situation of the patient.
Drug: Remifentanil + propofol
Remifentanil + propofol
Drug: Esketamine

Load dose of 0.25 mg/kg, and the fixed infusion rate of 0.15 mg/kg/h.The load dose will be injected intravenously within 1-2 minutes.Maintain the infusion at a fixed rate of 0.15 mg/kg/h for 72 hours; after 72 hours, change to a fixed rate infusion of 0.06 mg/kg/h.

Preparation: 46ml of saline + 4ml of eskeamine.

Other Names:
  • Esketamine Hydrochloride Injection
Procedure: Pain and Sedation Assessment

RASS Score:

After randomization success, a baseline Richmond Agitation-Sedation Scale (RASS) score is obtained before administering the investigational drug. Pain assessments are conducted every 1 hour within the first 6 hours after the initiation of the intravenous loading dose of the investigational drug, every 4 hours within the first 24 hours, and subsequently every 8 hours until the end of the study. In addition to the fixed time points mentioned above, researchers may conduct RASS scoring at any time based on the subject's actual condition (excessive or inadequate sedation). (No further RASS scoring is performed once the subject is fully awake.)

CPOT Score:

CPOT（Critical-Care Pain Observation Tool）Pain assessments are conducted concurrently with RASS scoring.
Placebo Comparator: remifentanil + propofol + saline
Remifentanil Hydrochloride for Injection (1mg;), propofol injection (50ml; 0.5g; )； The amount of saline used is equivalent to the amount of esketamine.All analgesic and sedative drugs used are adjusted according to the actual situation of the
Drug: Remifentanil + propofol
Remifentanil + propofol
Drug: Saline
As a placebo,normal saline at the same dose as esketamine.Saline is also administered intravenously.
Other Names:
  • physiological saline; saline solution
Procedure: Pain and Sedation Assessment

RASS Score:

After randomization success, a baseline Richmond Agitation-Sedation Scale (RASS) score is obtained before administering the investigational drug. Pain assessments are conducted every 1 hour within the first 6 hours after the initiation of the intravenous loading dose of the investigational drug, every 4 hours within the first 24 hours, and subsequently every 8 hours until the end of the study. In addition to the fixed time points mentioned above, researchers may conduct RASS scoring at any time based on the subject's actual condition (excessive or inadequate sedation). (No further RASS scoring is performed once the subject is fully awake.)

CPOT Score:

CPOT（Critical-Care Pain Observation Tool）Pain assessments are conducted concurrently with RASS scoring.

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
Doses of remifentanil and norepinephrine during mechanical ventilation (total dose/duration of use hours).
Time Frame: During mechanical ventilation procedure (From randomization to the seventh day of infusion or ventilator withdrawal, whichever occurs first）
Responsible researchers consult the patient's medical record after completing treatment to obtain the dosage and duration of medication.
During mechanical ventilation procedure (From randomization to the seventh day of infusion or ventilator withdrawal, 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
Duration of mechanical ventilation.
Time Frame: From endotracheal intubation to withdrawal from mechanical ventilation, or until 28 days after discharge, death, or randomization in the ICU, whichever occurs
Responsible researchers obtain information by viewing electronic medical records.
From endotracheal intubation to withdrawal from mechanical ventilation, or until 28 days after discharge, death, or randomization in the ICU, whichever occurs
Propofol dosage (total dose/duration of use) during mechanical ventilation.
Time Frame: During mechanical ventilation procedure (From randomization to the seventh day of infusion or ventilator withdrawal, whichever occurs first）
Responsible researchers consult the patient's medical record after completing treatment to obtain the dosage and duration of medication.
During mechanical ventilation procedure (From randomization to the seventh day of infusion or ventilator withdrawal, whichever occurs first）
The proportion of patients meeting the RASS sedation and CPOT pain goals during mechanical ventilation.
Time Frame: up to 28 days
Professionally trained researchers perform RASS and COPT scores on patients at specific time points.
up to 28 days
The incidence of delirium, i.e. the positive rate of CAM-ICU.
Time Frame: up to 28 days
The occurrence of delirium in patients will be recorded by clinicians or nurses on medical records, and researchers will summarize the occurrence of delirium (such as the time of occurrence, duration, treatment measures, etc.)Patients will be evaluated using CAM-ICU by clinicians or nurses.
up to 28 days
Incidence of adverse events.
Time Frame: up to 28 days
The occurrence of adverse events during the hospital period will be recorded in the medical record by the clinician or nurse, and the researcher will obtain the occurrence of adverse events (event type, time, treatment, results, etc.) through the medical record.
up to 28 days
The mortality rate
Time Frame: up to 28 days
Researchers obtain it through the hospital electronic system.
up to 28 days
Mechanical ventilator free days.
Time Frame: Days to 28
Responsible researchers obtain information by viewing electronic medical records.
Days to 28
Length of ICU stay.
Time Frame: up to 28 days
Researchers obtain it through the hospital electronic system.
up to 28 days

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.
Nanfang Hospital, Southern Medical 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.
May 31, 2023

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.
October 31, 2024

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.
October 31, 2024

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).
March 20, 2023

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.
May 1, 2023

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.
May 3, 2023

Study Record Updates

Last Update Posted (Estimated)

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.
November 22, 2023

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.
November 20, 2023

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.
November 1, 2023

More Information

Terms related to this study

Keywords

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.
  • NFEC-2022-394

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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