Immunoinflammatory Regulation of Esketamine in Septic Patients

Sepsis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04843982
• Other study ID #: YSY202001
• Status: Recruiting
• Phase: Phase 4
• Start date: July 28, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: Wuhan Union Hospital, China
• Contact: Jiancheng Zhang, PhD, MD
• Phone: +8613554105815
• Email: zhjcheng1[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Esketamine
• Immunosuppression
• Inflammatory Response
• Sepsis

Intervention

Drug:
• Esketamine hydrochloride
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.

Locations

Country	Name	City	State
China	Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum concentration of inflammatory cytokines (0 h)	Interleukin (IL)-6, tumor necrosis factor (TNF)-a, IL-2, IL-4, IL-10, IL-17A, and interferon (IFN)-?	0 hour after study inclusion
Primary	Serum concentration of inflammatory cytokines (48 h)	IL-6, TNF-a, IL-2, IL-4, IL-10, IL-17A, and IFN-?	48 hours after study inclusion
Primary	Serum concentration of inflammatory cytokines (72 h)	IL-6, TNF-a, IL-2, IL-4, IL-10, IL-17A, and IFN-?	72 hours after study inclusion
Primary	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
Primary	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
Primary	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
Primary	ICU length of stay	Length of stay in the ICU	up to 8 weeks
Secondary	Serum concentration of atrial natriuretic peptide (ANP) (0 h)	ANP is secreted primarily by atrial cardiomyocytes	0 hour after study inclusion
Secondary	Serum concentration of atrial natriuretic peptide (ANP) (48h)	ANP is secreted primarily by atrial cardiomyocytes	48 hours after study inclusion
Secondary	Serum concentration of atrial natriuretic peptide (ANP) (72h)	ANP is secreted primarily by atrial cardiomyocytes	72 hours after study inclusion
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	0 hour after study inclusion
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	24 hours after study inclusion
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	48 hours after study inclusion
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	72 hours after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	0 hour after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	24 hours after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	48 hours after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	72 hours after study inclusion
Secondary	Mechanical ventilation time after inclusion	Patients requiring mechanical ventilation after study inclusion	Up to 8 weeks
Secondary	Total hospital length of stay	Total length of hospital stay	Through study completion, an average of 2 year
Secondary	Infection complications	Pulmonary infection, urinary tract infection, bloodstream infections, etc	Through study completion, an average of 2 year
Secondary	In-hospital mortality	Mortality rates for the entire period of hospitalization	Through study completion, an average of 2 year
Secondary	90-day readmission rate	Percentage of readmission to hospital within 90 days of study inclusion	Through study completion, an average of 2 year
Secondary	CCL1 expression in alveolar macrophages (0 h)	CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid	0 hour after study inclusion
Secondary	CCL1 expression in alveolar macrophages (24 h)	CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid	24 hours after study inclusion
Secondary	CCL1 expression in alveolar macrophages (72 h)	CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid	72 hours after study inclusion
Secondary	expression of WNT pathway proteins in alveolar macrophages (0 h)	Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid	0 hour after study inclusion
Secondary	expression of WNT pathway proteins in alveolar macrophages (24 h)	Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid	24 hours after study inclusion
Secondary	expression of WNT pathway proteins in alveolar macrophages (72 h)	Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid	72 hours after study inclusion