Adjunctive Esketamine for Analgesia in Mechanically Ventilated Septic Shock Patients

NCT05839366 | Unknown Phase 3

• 1 other identifier: NFEC-2022-394
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock; Mechanical Ventilation Complication

Keywords

Esketamine; Vasoactive drugs; sedation; analgesia

Outcome Measures

Primary Outcomes (1)

• Doses of remifentanil and norepinephrine during mechanical ventilation (total dose/duration of use hours).

  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 Outcomes (8)

• Duration of mechanical ventilation.

  From endotracheal intubation to withdrawal from mechanical ventilation, or until 28 days after discharge, death, or randomization in the ICU, whichever occurs

• Mechanical ventilator free days.

  Days to 28

• Propofol dosage (total dose/duration of use) during mechanical ventilation.

  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.

  up to 28 days

• The incidence of delirium, i.e. the positive rate of CAM-ICU.

  up to 28 days

Study Arms (2)

Remifentanil + propofol + esketamine

ACTIVE COMPARATOR

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: Esketamine; Drug: Remifentanil + propofol; Procedure: Pain and Sedation Assessment

remifentanil + propofol + saline

PLACEBO COMPARATOR

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: Saline; Drug: Remifentanil + propofol; Procedure: Pain and Sedation Assessment

Interventions

Esketamine DRUG

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.

Also known as: Esketamine Hydrochloride Injection

Remifentanil + propofol + esketamine

Saline DRUG

As a placebo,normal saline at the same dose as esketamine.Saline is also administered intravenously.

Also known as: physiological saline; saline solution

remifentanil + propofol + saline

Remifentanil + propofol DRUG

Remifentanil + propofol

Remifentanil + propofol + esketamine; remifentanil + propofol + saline

Pain and Sedation Assessment PROCEDURE

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.

Remifentanil + propofol + esketamine; remifentanil + propofol + saline

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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).

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Southern medical university Nanfang hospital

Guangzhou, 510515, China

RECRUITING

MeSH Terms

Conditions

Shock, Septic; Agnosia

Interventions

Esketamine; Sodium Chloride; Saline Solution; Remifentanil; Propofol

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Hongbin Hu, doctor

CONTACT

+86139224837; hobewoos@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: May 3, 2023
• Study Start: May 31, 2023
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: November 22, 2023

Record last verified: 2023-11

Locations

CN (1)