Sepsis in Critically Ill Patients

Official title

A Prospective Multicenter Registration Study on Sepsis in Critically Ill Patients

Overview

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection, and remains the leading cause of death in critical care medicine worldwide. According to the 2024 Global Burden of Disease data, there are 48.9 million new cases and 11 million deaths annually worldwide, with 11 million deaths accounting for 19.7% of all global deaths. In China, the incidence of sepsis continues to rise due to population aging, increased invasive procedures, overuse of antimicrobials, the prevalence of multidrug-resistant organisms, and a growing number of patients with chronic diseases. Regional studies indicate that the incidence of sepsis in Chinese ICUs ranges from 15% to 30%, with mortality rates as high as 40% to 60%-far exceeding those in developed countries. Among critically ill patients admitted to the ICU-such as those with severe trauma, major surgery, acute respiratory distress syndrome, severe pancreatitis, and advanced malignancies-hospital-acquired infections leading to secondary sepsis represent the most critical trigger for clinical deterioration, multiple organ dysfunction syndrome (MODS), and death. This creates a vicious cascade of "primary disease exacerbation → nosocomial infection → sepsis → MODS → death", resulting in skyrocketing costs, prolonged hospital stays, and heavy burdens on families and society. To address this challenge, this project aims to: (1) establish the largest and internationally leading multimodal dataset for severe sepsis in China, covering 19 tertiary ICUs nationwide over a 5-year period, with 5,300 critically ill patients including 800 sepsis cases, integrating clinical data, immunological indicators, biomarkers, microbiological data, imaging, longitudinal biospecimens, and long-term follow-up information into a standardized, shareable, and sustainable national sepsis database; (2) systematically elucidate the three core pathophysiological mechanisms of severe sepsis-identifying risk factors, pathogen profiles, antimicrobial resistance patterns, and early warning indicators; revealing the dynamic dysregulation patterns of cellular immunity, humoral immunity, and innate immunity to establish immunophenotyping standards; and clarifying the risk factors, mechanisms, and subtype characteristics of multiple organ injury; (3) foster interdisciplinary collaboration between medical and engineering sciences to develop a series of precision diagnostic and therapeutic tools, including AI-assisted early infection warning systems, rapid immunotyping assays, multi-organ injury prediction models, and individualized prognostic calculators for real-time, accurate, and non-invasive bedside assessment; (4) establish a comprehensive precision management system for sepsis, forming an integrated "prevention-early warning-diagnosis-immunotyping-stratified treatment-prognostic evaluation-rehabilitation" care pathway; (5) drive clinical translation to improve patient outcomes, aiming to reduce ICU sepsis incidence, mortality, and healthcare costs, while improving long-term quality of life, cognitive function, and psychological status of survivors and reducing readmission rates; and (6) build a national-level sepsis research platform and cultivate talent by establishing a nationwide collaborative research network, and training professionals with integrated clinical-research-translational competencies.

Interventions

• Other Not applicable- observational study
  Not applicable- observational study

Primary outcome measures

• Annual incidence of sepsis in ICU [Time frame: 90 days after enrollment.]
• Prevalence of sepsis in ICU [Time frame: 90 days after enrollment]
• Distribution of infection site (lung/abdominal/bloodstream/urinary tract) [Time frame: 90 days after enrollment]
• Distribution of infection type (community-acquired/hospital-acquired/secondary) [Time frame: 90 days after enrollment]
• Pathogen distribution (Gram-negative/Gram-positive/fungal) [Time frame: 90 days after enrollment]
• Antimicrobial resistance rate (CRE/CRAB/MRSA) [Time frame: 90 days after enrollment]
• ICU length of stay [Time frame: Through ICU discharge, up to 90 days]
• Total hospital length of stay [Time frame: Through hospital discharge, up to 90 days]
• Duration of mechanical ventilation [Time frame: Through 90 days]
• Duration of vasoactive agent use [Time frame: Through 90 days]

Secondary outcome measures (12)

• CD3+ T Lymphocyte Count/Percentage [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• CD4+ T Lymphocyte Count/Percentage [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• CD8+ T Lymphocyte Count/Percentage [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• CD4+/CD8+ Ratio [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Regulatory T Cell (Treg) Percentage [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Th1/Th2 Ratio [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Monocyte HLA-DR (mHLA-DR) Expression [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Natural Killer (NK) Cell Count/Percentage [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Absolute Lymphocyte Count [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Lymphocyte Apoptosis Rate [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Monocyte Phagocytic Index [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]
• Serum Ferritin Concentration [Time frame: At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years;
• ICU stay ≥ 24 hours;
• Informed consent signed by the patient or their legal representative

Exclusion criteria

• ICU stay < 24 hours;
• Refusal to provide informed consent;
• Pregnancy or lactation;
• Receiving palliative care or expected survival < 24 hours;
• Previously enrolled in this study;
• Severe immunodeficiency (HIV infection, or long-term use of corticosteroids/immunosuppressants).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Beijing Chao Yang Hospital — Beijing

Identifiers

NCT: NCT07707622 · CriticalPatientSepsis

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗