Clinical trial NCT04843982: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Esketamine
Sepsis
Inflammatory Response
Immunosuppression
Keywords: Esketamine
Sepsis
Inflammatory Response
Immunosuppression
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2021-04-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Serum concentration of inflammatory cytokines (0 h)
timeFrame: 0 hour after study inclusion
measure: Serum concentration of inflammatory cytokines (48 h)
timeFrame: 48 hours after study inclusion
measure: Serum concentration of inflammatory cytokines (72 h)
timeFrame: 72 hours after study inclusion
measure: Absolute number of lymphocyte subsets in the peripheral blood (0 h)
timeFrame: 0 hour after study inclusion
measure: Absolute number of lymphocyte subsets in the peripheral blood (48 h)
timeFrame: 48 hours after study inclusion
measure: Absolute number of lymphocyte subsets in the peripheral blood (72 h)
timeFrame: 72 hours after study inclusion
measure: ICU length of stay
timeFrame: up to 8 weeks
Secondary outcomes:
measure: Serum concentration of atrial natriuretic peptide (ANP) (0 h)
timeFrame: 0 hour after study inclusion
measure: Serum concentration of atrial natriuretic peptide (ANP) (48h)
timeFrame: 48 hours after study inclusion
measure: Serum concentration of atrial natriuretic peptide (ANP) (72h)
timeFrame: 72 hours after study inclusion
measure: Acute physiology and chronic health evaluation (APACHE) Ⅱ score
timeFrame: 0 hour after study inclusion
measure: Acute physiology and chronic health evaluation (APACHE) Ⅱ score
timeFrame: 24 hours after study inclusion
measure: Acute physiology and chronic health evaluation (APACHE) Ⅱ score
timeFrame: 48 hours after study inclusion
measure: Acute physiology and chronic health evaluation (APACHE) Ⅱ score
timeFrame: 72 hours after study inclusion
measure: Sequential organ failure assessment (SOFA) score
timeFrame: 0 hour after study inclusion
measure: Sequential organ failure assessment (SOFA) score
timeFrame: 24 hours after study inclusion
measure: Sequential organ failure assessment (SOFA) score
timeFrame: 48 hours after study inclusion
measure: Sequential organ failure assessment (SOFA) score
timeFrame: 72 hours after study inclusion
measure: Mechanical ventilation time after inclusion
timeFrame: Up to 8 weeks
measure: Total hospital length of stay
timeFrame: Through study completion, an average of 2 year
measure: Infection complications
timeFrame: Through study completion, an average of 2 year
measure: In-hospital mortality
timeFrame: Through study completion, an average of 2 year
measure: 90-day readmission rate
timeFrame: Through study completion, an average of 2 year
measure: CCL1 expression in alveolar macrophages (0 h)
timeFrame: 0 hour after study inclusion
measure: CCL1 expression in alveolar macrophages (24 h)
timeFrame: 24 hours after study inclusion
measure: CCL1 expression in alveolar macrophages (72 h)
timeFrame: 72 hours after study inclusion
measure: expression of WNT pathway proteins in alveolar macrophages (0 h)
timeFrame: 0 hour after study inclusion
measure: expression of WNT pathway proteins in alveolar macrophages (24 h)
timeFrame: 24 hours after study inclusion
measure: expression of WNT pathway proteins in alveolar macrophages (72 h)
timeFrame: 72 hours after study inclusion
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Shiying Yuan, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: