Septic ShockPhase 3NCT05839366
Adjunctive Esketamine for Analgesia in Mechanically Ventilated Septic Shock Patients
A Phase 3 study testing Esketamine, Saline and Remifentanil + propofol in people with Septic Shock and Mechanical Ventilation Complication, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Mechanical Ventilation Complication
- What is being tested?
- Esketamine, Saline and Remifentanil + propofol
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 1 siteChina
- Study dates
- 31 May 2023to 31 Oct 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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;
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- 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).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Southern medical university Nanfang hospital
Guangzhou, 510515
Hongbin Hu, doctor, +8613922483752, hobewoos@163.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Septic Shock, Mechanical Ventilation Complication
- Being tested
- Esketamine, Saline, Remifentanil + propofol, Pain and Sedation Assessment
- Keywords
- Esketamine, Vasoactive drugs, sedation, analgesia
- Medical subject headings
- Shock, Septic, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsketamineDrug
Also called Esketamine Hydrochloride Injection
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.
SalineDrug
Also called physiological saline; saline solution
As a placebo,normal saline at the same dose as esketamine.Saline is also administered intravenously.
Remifentanil + propofolDrug
Remifentanil + propofol
Pain and Sedation AssessmentProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Saline; Drug: Remifentanil + propofol; Procedure: Pain and Sedation Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Responsible researchers obtain information by viewing electronic medical records.
Measured: 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.
Responsible researchers obtain information by viewing electronic medical records.
Measured: Days to 28
Propofol dosage (total dose/duration of use) during mechanical ventilation.
Responsible researchers consult the patient's medical record after completing treatment to obtain the dosage and duration of medication.
Measured: 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.
Professionally trained researchers perform RASS and COPT scores on patients at specific time points.
Measured: up to 28 days
The incidence of delirium, i.e. the positive rate of CAM-ICU.
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.
Measured: up to 28 days
Incidence of adverse events.
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.
Measured: up to 28 days
Length of ICU stay.
Researchers obtain it through the hospital electronic system.
Measured: up to 28 days
The mortality rate
Researchers obtain it through the hospital electronic system.
Measured: up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study start31 May 2023
- Primary completion31 Oct 2024 (estimated)
- Study completion31 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05839366
- Sponsor's protocol ID
- NFEC-2022-394
- Status last verified
- Nov 2023
- First submitted
- 20 Mar 2023
- Last updated
- 22 Nov 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Esketamine for Analgesia in Mechanically Ventilated ICU Septic Shock Patients
- ClinicalTrials.gov ID
- NCT05839366
- Acronym / sponsor ID
- NFEC-2022-394
- Conditions
- Septic Shock, Mechanical Ventilation Complication
- Keywords
- Esketamine, Vasoactive drugs, sedation, analgesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Study start
- 31 May 2023 (actual)
- Primary completion
- 31 Oct 2024 (estimated)
- Study completion
- 31 Oct 2024 (estimated)
- First posted
- 3 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Remifentanil + propofol + esketamine | Active comparator | Drug: Esketamine, Drug: Remifentanil + propofol, Procedure: Pain and Sedation Assessmentesketamine (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. |
| remifentanil + propofol + saline | Placebo comparator | Drug: Saline, Drug: Remifentanil + propofol, Procedure: Pain and Sedation AssessmentRemifentanil 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsketamineAlso: Esketamine Hydrochloride InjectionLoad 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. | Drug | Remifentanil + propofol + esketamine |
| SalineAlso: physiological saline; saline solutionAs a placebo,normal saline at the same dose as esketamine.Saline is also administered intravenously. | Drug | remifentanil + propofol + saline |
| Remifentanil + propofolRemifentanil + propofol | Drug | Remifentanil + propofol + esketamine, remifentanil + propofol + saline |
| Pain and Sedation AssessmentRASS 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. | Procedure or surgery | Remifentanil + propofol + esketamine, remifentanil + propofol + saline |
Primary outcome
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.
8 secondary outcomes
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
Mechanical ventilator free days.
Time frame: Days to 28
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）
The proportion of patients meeting the RASS sedation and CPOT pain goals during mechanical ventilation.
Time frame: up to 28 days
The incidence of delirium, i.e. the positive rate of CAM-ICU.
Time frame: up to 28 days
Incidence of adverse events.
Time frame: up to 28 days
Length of ICU stay.
Time frame: up to 28 days
The mortality rate
Time frame: up to 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Esketamine, Saline and Remifentanil + propofol in people with Septic Shock and Mechanical Ventilation Complication, run by Nanfang Hospital, Southern Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hongbin Hu, doctor (+86139224837, hobewoos@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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）). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.