Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Sponsor

Wuhan Union Hospital, China (Other)

Overall Status

Recruiting

CT.gov ID

NCT05875740

Collaborator

(none)

Enrollment

Location

24.4

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis.

Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice.

This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.

Condition or Disease	Intervention/Treatment	Phase
Sepsis Inflammatory Response

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Anticipated Study Start Date :

May 20, 2023

Anticipated Primary Completion Date :

Apr 30, 2025

Anticipated Study Completion Date :

May 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
septic patients patients with sepsis defined based on Sepsis 3.0 criteria within 24 hours after admission
non-septic patients patients without sepsis defined based on Sepsis 3.0 criteria within 24 hours after admission
healthy control group healthy adults

Outcome Measures

Primary Outcome Measures

Absolute number of CD8+T subsets in the peripheral blood (0 hour) [0 hour after study inclusion]
CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells
Absolute number of CD8+T subsets in the peripheral blood (24 hours) [24 hours after study inclusion]
CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells
Absolute number of CD8+T subsets in the peripheral blood (48 hours) [48 hours after study inclusion]
CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells
Absolute number of CD8+T subsets in the peripheral blood (72 hours) [72 hours after study inclusion]
CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells
proliferation of CD8+T subsets in the peripheral blood (0 hour) [0 hour after study inclusion]
expression of Ki67 in Tcm and Tem
proliferation of CD8+T subsets in the peripheral blood (24 hours) [24 hours after study inclusion]
expression of Ki67 in Tcm and Tem
proliferation of CD8+T subsets in the peripheral blood (48 hours) [48 hours after study inclusion]
expression of Ki67 in Tcm and Tem
proliferation of CD8+T subsets in the peripheral blood (72 hours) [72 hours after study inclusion]
expression of Ki67 in Tcm and Tem
ICU length of stay [up to 4 weeks]
Length of stay in the ICU

Secondary Outcome Measures

Mechanical ventilation time after inclusion [up to 4 weeks]
Patients requiring mechanical ventilation after study inclusion
Total hospital length of stay [up to 4 weeks]
Total length of hospital stay
In-hospital mortality [up to 4 weeks]
Mortality rates for the entire period of hospitalization
90-day readmission rate [up to 4 weeks]
Percentage of readmission to hospital within 90 days of study inclusion
Infection complications [up to 4 weeks]
Pulmonary infection, urinary tract infection, bloodstream infections, etc
Acute physiology and chronic health evaluation (APACHE) Ⅱ score [0h after study inclusion]
0-67, higher scores correspond to more severe disease and a higher risk of death
Acute physiology and chronic health evaluation (APACHE) Ⅱ score [24 hours after study inclusion]
0-67, higher scores correspond to more severe disease and a higher risk of death
Acute physiology and chronic health evaluation (APACHE) Ⅱ score [48 hours after study inclusion]
0-67, higher scores correspond to more severe disease and a higher risk of death
Acute physiology and chronic health evaluation (APACHE) Ⅱ score [72 hours after study inclusion]
0-67, higher scores correspond to more severe disease and a higher risk of death
Sequential organ failure assessment (SOFA) score [0 hour after study inclusion]
0-43, higher scores correspond to more severe sepsis
Sequential organ failure assessment (SOFA) score [24 hours after study inclusion]
0-43, higher scores correspond to more severe sepsis
Sequential organ failure assessment (SOFA) score [48 hours after study inclusion]
0-43, higher scores correspond to more severe sepsis
Sequential organ failure assessment (SOFA) score [72 hours after study inclusion]
0-43, higher scores correspond to more severe sepsis
Plasma cytokine levels [0 hour after study inclusion]
IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α
Plasma cytokine levels [24 hours after study inclusion]
IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α
Plasma cytokine levels [48 hours after study inclusion]
IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α
Plasma cytokine levels [72 hours after study inclusion]
IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients aged 18-60 years old without restriction of gender, race, religion, creed or nationality; No sedative drugs with elimination half-life were used before inclusion in the study; Patients and/or their family members know and agree to participate in the trial.

Exclusion Criteria:

History of solid organ or bone marrow transplantation; Diseases that may affect immune-related indicators, such as autoimmune diseases such as rheumatoid arthritis and SLE, or hematological malignancies such as leukemia and lymphoma; Have received radiotherapy or chemotherapy within the past 30 days, or have received immunosuppressive drugs (tripterygium, mycophenolate, cyclophosphamide, FK506, etc); Pregnancy or lactation; Chronic nephrosis; Severe chronic liver disease (child-Pugh: Grade C); alcohol or opioid dependence, mental illness, or severe cognitive impairment; Patients and/or their family members refuse to participate in the trial.