Immunoinflammatory Regulation of Esketamine in Septic Patients

NCT04843982 | Recruiting Phase 4 DMC

• 1 other identifier: YSY202001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

Esketamine; Sepsis; Inflammatory Response; Immunosuppression

Keywords

Esketamine; Sepsis; Inflammatory Response; Immunosuppression

Outcome Measures

Primary Outcomes (7)

• 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

  0 hour after study inclusion

• Serum concentration of inflammatory cytokines (48 h)

  IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ

  48 hours after study inclusion

• Serum concentration of inflammatory cytokines (72 h)

  IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ

  72 hours after study inclusion

• Absolute number of lymphocyte subsets in the peripheral blood (0 h)

  CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells

  0 hour after study inclusion

• Absolute number of lymphocyte subsets in the peripheral blood (48 h)

  CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells

  48 hours after study inclusion

• Absolute number of lymphocyte subsets in the peripheral blood (72 h)

  CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells

  72 hours after study inclusion

• ICU length of stay

  Length of stay in the ICU

  up to 8 weeks

Secondary Outcomes (22)

• Serum concentration of atrial natriuretic peptide (ANP) (0 h)

  0 hour after study inclusion

• Serum concentration of atrial natriuretic peptide (ANP) (48h)

  48 hours after study inclusion

• Serum concentration of atrial natriuretic peptide (ANP) (72h)

  72 hours after study inclusion

• Acute physiology and chronic health evaluation (APACHE) Ⅱ score

  0 hour after study inclusion

• Acute physiology and chronic health evaluation (APACHE) Ⅱ score

  24 hours after study inclusion

Study Arms (2)

esketamine plus propofol

EXPERIMENTAL

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.

Drug: Esketamine hydrochloride

propofol

NO INTERVENTION

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).

Interventions

Esketamine hydrochloride DRUG

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.

esketamine plus propofol

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (2)

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

Wuhan, Hubei, 430022, China

NOT YET RECRUITING

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

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shiying Yuan, PhD, MD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiancheng Zhang, PhD, MD

CONTACT

+8613554105815; zhjcheng1@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 14, 2021
• Study Start: July 28, 2021
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Six months after the paper was published
• 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.

Locations

CN (2)