search
Back to results

Immunoinflammatory Regulation of Esketamine in Septic Patients

Primary Purpose

Esketamine, Sepsis, Inflammatory Response

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Esketamine hydrochloride
Sponsored by
Wuhan Union Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esketamine focused on measuring Esketamine, Sepsis, Inflammatory Response, Immunosuppression

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 18 years old ≤ age ≤60 years old;
  • SOFA score ≥2;
  • Mechanical ventilation should be required for at least 24 hours when included in the study;
  • Informed consent is obtained.

Exclusion Criteria:

  • Age < 18 years old or ≥ 60 years old;
  • Previous solid organ or bone marrow transplantation;
  • Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), or hematologic malignancies (leukemia and lymphoma, etc.);
  • Received radiotherapy or chemotherapy within the past 30 days, or received immunosuppressant drugs (tripterygium wilfordii, mycophenolate mofetil, cyclophosphamide, FK506, etc.), or continuous treatment with prednisolone more than 10 mg/day (or equivalent doses of the other hormones);
  • Unstable angina pectoris or myocardial infarction in the past six months;
  • Acute brain injury (traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, acute intracranial hemorrhage, acute intracranial infection, etc.);
  • Poorly controlled hypertension and congestive heart failure;
  • Increased intraocular or intracranial pressure;
  • Chronic kidney disease, received continuous renal replacement therapy in the past 30 days, or acute renal failure requiring CRRT;
  • Severe chronic liver disease (Child-Pugh class B or C);
  • Alcohol dependence, mental illness or severe cognitive impairment;
  • Pregnancy or lactation;
  • Informed consent is not obtained.

Sites / Locations

  • Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

esketamine plus propofol

propofol

Arm Description

After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2). After inclusion, septic patients will be received a single intravenous injection of esketamine (0.7 mg/kg), and then followed by an intravenous administration of esketamine (0.07 mg/kg/h) with an infusion pump for three consecutive days.

After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2).

Outcomes

Primary Outcome Measures

Serum concentration of inflammatory cytokines (0 h)
Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-10, IL-17A, and interferon (IFN)-γ
Serum concentration of inflammatory cytokines (48 h)
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ
Serum concentration of inflammatory cytokines (72 h)
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ
Absolute number of lymphocyte subsets in the peripheral blood (0 h)
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Absolute number of lymphocyte subsets in the peripheral blood (48 h)
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Absolute number of lymphocyte subsets in the peripheral blood (72 h)
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
ICU length of stay
Length of stay in the ICU

Secondary Outcome Measures

Serum concentration of atrial natriuretic peptide (ANP) (0 h)
ANP is secreted primarily by atrial cardiomyocytes
Serum concentration of atrial natriuretic peptide (ANP) (48h)
ANP is secreted primarily by atrial cardiomyocytes
Serum concentration of atrial natriuretic peptide (ANP) (72h)
ANP is secreted primarily by atrial cardiomyocytes
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
0-67, higher scores correspond to more severe disease and a higher risk of death
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
0-67, higher scores correspond to more severe disease and a higher risk of death
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
0-67, higher scores correspond to more severe disease and a higher risk of death
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
0-67, higher scores correspond to more severe disease and a higher risk of death
Sequential organ failure assessment (SOFA) score
0-43, higher scores correspond to more severe sepsis
Sequential organ failure assessment (SOFA) score
0-43, higher scores correspond to more severe sepsis
Sequential organ failure assessment (SOFA) score
0-43, higher scores correspond to more severe sepsis
Sequential organ failure assessment (SOFA) score
0-43, higher scores correspond to more severe sepsis
Mechanical ventilation time after inclusion
Patients requiring mechanical ventilation after study inclusion
Total hospital length of stay
Total length of hospital stay
Infection complications
Pulmonary infection, urinary tract infection, bloodstream infections, etc
In-hospital mortality
Mortality rates for the entire period of hospitalization
90-day readmission rate
Percentage of readmission to hospital within 90 days of study inclusion

Full Information

First Posted
March 29, 2021
Last Updated
September 5, 2023
Sponsor
Wuhan Union Hospital, China
search

1. Study Identification

Unique Protocol Identification Number
NCT04843982
Brief Title
Immunoinflammatory Regulation of Esketamine in Septic Patients
Official Title
Effects of Esketamine Combined With Propofol for Sedation on Systemic Inflammation and Immune Function in Septic Patients in the ICU: a Single-center, Non-blind, Prospective Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wuhan Union Hospital, China

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Studies have shown that excessive systemic inflammatory response and concomitant immunosuppression are the main cause of early death in patients with sepsis. Therefore, it is very important to reduce excessive inflammation and improve immunosuppression in the acute phase of sepsis. Clinical studies have shown that esketamine combined with propofol for sedation has been proven to be safe and effective for septic patients in the ICU due to its cardiovascular stability. Previous studies have demonstrated that esketamine has anti-inflammatory effects against depression and surgical stress. Our preliminary experimental studies have found that esketamine had strong anti-inflammatory effects in the acute phase of sepsis. However, it is not clear whether esketamine could reduce excessive inflammation and improve immunosuppression in septic patients primarily sedated with a continuous infusion of propofol. This intervention study is to investigate whether three consecutive days of intravenous esketamine infusions via infusion pump (0.07 mg/kg/h) could reduce excessive inflammation and improve immunosuppression in septic patients requiring mechanical ventilation in the ICU under sedation primarily with propofol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esketamine, Sepsis, Inflammatory Response, Immunosuppression
Keywords
Esketamine, Sepsis, Inflammatory Response, Immunosuppression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
esketamine plus propofol
Arm Type
Experimental
Arm Description
After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2). After inclusion, septic patients will be received a single intravenous injection of esketamine (0.7 mg/kg), and then followed by an intravenous administration of esketamine (0.07 mg/kg/h) with an infusion pump for three consecutive days.
Arm Title
propofol
Arm Type
No Intervention
Arm Description
After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2).
Intervention Type
Drug
Intervention Name(s)
Esketamine hydrochloride
Intervention Description
After inclusion, septic patients will be received a single intravenous injection of esketamine (0.7 mg/kg), and then followed by an intravenous administration of esketamine (0.07 mg/kg/h) with an infusion pump for three consecutive days.
Primary Outcome Measure Information:
Title
Serum concentration of inflammatory cytokines (0 h)
Description
Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-10, IL-17A, and interferon (IFN)-γ
Time Frame
0 hour after study inclusion
Title
Serum concentration of inflammatory cytokines (48 h)
Description
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ
Time Frame
48 hours after study inclusion
Title
Serum concentration of inflammatory cytokines (72 h)
Description
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ
Time Frame
72 hours after study inclusion
Title
Absolute number of lymphocyte subsets in the peripheral blood (0 h)
Description
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Time Frame
0 hour after study inclusion
Title
Absolute number of lymphocyte subsets in the peripheral blood (48 h)
Description
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Time Frame
48 hours after study inclusion
Title
Absolute number of lymphocyte subsets in the peripheral blood (72 h)
Description
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Time Frame
72 hours after study inclusion
Title
ICU length of stay
Description
Length of stay in the ICU
Time Frame
up to 8 weeks
Secondary Outcome Measure Information:
Title
Serum concentration of atrial natriuretic peptide (ANP) (0 h)
Description
ANP is secreted primarily by atrial cardiomyocytes
Time Frame
0 hour after study inclusion
Title
Serum concentration of atrial natriuretic peptide (ANP) (48h)
Description
ANP is secreted primarily by atrial cardiomyocytes
Time Frame
48 hours after study inclusion
Title
Serum concentration of atrial natriuretic peptide (ANP) (72h)
Description
ANP is secreted primarily by atrial cardiomyocytes
Time Frame
72 hours after study inclusion
Title
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Description
0-67, higher scores correspond to more severe disease and a higher risk of death
Time Frame
0 hour after study inclusion
Title
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Description
0-67, higher scores correspond to more severe disease and a higher risk of death
Time Frame
24 hours after study inclusion
Title
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Description
0-67, higher scores correspond to more severe disease and a higher risk of death
Time Frame
48 hours after study inclusion
Title
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Description
0-67, higher scores correspond to more severe disease and a higher risk of death
Time Frame
72 hours after study inclusion
Title
Sequential organ failure assessment (SOFA) score
Description
0-43, higher scores correspond to more severe sepsis
Time Frame
0 hour after study inclusion
Title
Sequential organ failure assessment (SOFA) score
Description
0-43, higher scores correspond to more severe sepsis
Time Frame
24 hours after study inclusion
Title
Sequential organ failure assessment (SOFA) score
Description
0-43, higher scores correspond to more severe sepsis
Time Frame
48 hours after study inclusion
Title
Sequential organ failure assessment (SOFA) score
Description
0-43, higher scores correspond to more severe sepsis
Time Frame
72 hours after study inclusion
Title
Mechanical ventilation time after inclusion
Description
Patients requiring mechanical ventilation after study inclusion
Time Frame
Up to 8 weeks
Title
Total hospital length of stay
Description
Total length of hospital stay
Time Frame
Through study completion, an average of 2 year
Title
Infection complications
Description
Pulmonary infection, urinary tract infection, bloodstream infections, etc
Time Frame
Through study completion, an average of 2 year
Title
In-hospital mortality
Description
Mortality rates for the entire period of hospitalization
Time Frame
Through study completion, an average of 2 year
Title
90-day readmission rate
Description
Percentage of readmission to hospital within 90 days of study inclusion
Time Frame
Through study completion, an average of 2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years old ≤ age ≤60 years old; SOFA score ≥2; Mechanical ventilation should be required for at least 24 hours when included in the study; Informed consent is obtained. Exclusion Criteria: Age < 18 years old or ≥ 60 years old; Previous solid organ or bone marrow transplantation; Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), or hematologic malignancies (leukemia and lymphoma, etc.); Received radiotherapy or chemotherapy within the past 30 days, or received immunosuppressant drugs (tripterygium wilfordii, mycophenolate mofetil, cyclophosphamide, FK506, etc.), or continuous treatment with prednisolone more than 10 mg/day (or equivalent doses of the other hormones); Unstable angina pectoris or myocardial infarction in the past six months; Acute brain injury (traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, acute intracranial hemorrhage, acute intracranial infection, etc.); Poorly controlled hypertension and congestive heart failure; Increased intraocular or intracranial pressure; Chronic kidney disease, received continuous renal replacement therapy in the past 30 days, or acute renal failure requiring CRRT; Severe chronic liver disease (Child-Pugh class B or C); Alcohol dependence, mental illness or severe cognitive impairment; Pregnancy or lactation; Informed consent is not obtained.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jiancheng Zhang, PhD, MD
Phone
+8613554105815
Email
zhjcheng1@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shiying Yuan, PhD, MD
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiancheng Zhang, PhD, MD
Phone
+8613554105815
Email
zhjcheng1@126.com
Facility Name
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiancheng Zhang, Dr.
Phone
+8613554105815
Email
zhjcheng1@126.com
First Name & Middle Initial & Last Name & Degree
Jiancheng Zhang, Dr.

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
After the completion of the study, the original data will be sent to the email address: zhjcheng1@163.com, and the password will be provided after the paper is published.
IPD Sharing Time Frame
Six months after the paper was published
IPD Sharing Access Criteria
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Learn more about this trial

Immunoinflammatory Regulation of Esketamine in Septic Patients

We'll reach out to this number within 24 hrs