Sepsis in Critically Ill Patients

NCT07707622 | Enrolling By Invitation DMC

• 1 other identifier: CriticalPatientSepsis
• Study Type: observational
• Target: 2,400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sepsis

Outcome Measures

Primary Outcomes (39)

• Annual incidence of sepsis in ICU

  Number of new sepsis cases (diagnosed by Sepsis-3 criteria) per 1,000 ICU admissions (or per 1,000 patient-days).

  90 days after enrollment.

• Prevalence of sepsis in ICU

  Percentage of ICU admissions meeting Sepsis-3 criteria for sepsis during the study period.

  90 days after enrollment

• Distribution of infection site (lung/abdominal/bloodstream/urinary tract)

  Percentage of patients with infection originating from the lung, abdomen, bloodstream, or urinary tract, respectively.

  90 days after enrollment

• Distribution of infection type (community-acquired/hospital-acquired/secondary)

  Percentage of patients with community-acquired, hospital-acquired, or secondary infection, respectively.

  90 days after enrollment

• Pathogen distribution (Gram-negative/Gram-positive/fungal)

  Percentage of microbiological isolates classified as Gram-negative bacteria, Gram-positive bacteria, or fungi.

  90 days after enrollment

• Antimicrobial resistance rate (CRE/CRAB/MRSA)

  Percentage of isolates identified as carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), or methicillin-resistant Staphylococcus aureus (MRSA).

  90 days after enrollment

• ICU length of stay

  Number of days from ICU admission to ICU discharge.

  Through ICU discharge, up to 90 days

• Total hospital length of stay

  Number of days from hospital admission to hospital discharge.

  Through hospital discharge, up to 90 days

• Duration of mechanical ventilation

  Number of days on invasive mechanical ventilation.

  Through 90 days

• Duration of vasoactive agent use

  Number of days on any vasoactive agent (e.g., norepinephrine, vasopressin, dobutamine, epinephrine).

  Through 90 days

• Duration of renal replacement therapy

  Number of days receiving renal replacement therapy (continuous or intermittent).

  Through 90 days

• Daily ICU cost

  Average direct cost of ICU care per patient per day, in Chinese Yuan (CNY).

  Through ICU discharge, up to 90 days

• Total hospitalization cost

  Total direct cost of hospital care per patient, in Chinese Yuan (CNY), from hospital admission to discharge.

  Through hospital discharge, up to 90 days

• ICU mortality

  Percentage of patients who die prior to ICU discharge.

  Through ICU discharge, an average of 28 days

• In-hospital mortality

  Percentage of patients who die prior to hospital discharge.

  Through hospital discharge, up to 90 days

• 28-day all-cause mortality

  Percentage of patients who die from any cause within 28 days of enrollment.

  28 days after enrollment

• 90-day all-cause mortality

  Percentage of patients who die from any cause within 90 days of enrollment.

  90 days after enrollment

• Discriminative Performance of the Infection Risk-Prediction Model

  Area under the receiver operating characteristic curve (AUC/C-statistic) of the multivariable model predicting infection occurrence, developed from patient, disease, and treatment-related candidate predictors using Cox regression, LASSO, and propensity score analysis.

  90 days after enrollment

• Sensitivity and Specificity of the Infection Risk-Prediction Score

  Sensitivity and specificity (%) of the infection risk-prediction score at its optimal cutoff value, determined by the Youden index.

  90 days after enrollment

• Hand Hygiene Compliance Rate

  Percentage of observed hand hygiene opportunities performed correctly, per WHO Five Moments guidance.

  90 days after enrollment

• Catheter Care Bundle Compliance Rate

  Percentage of eligible patient-days with full compliance to central line and urinary catheter care bundle elements.

  90 days after enrollment

• Diagnostic Accuracy of Procalcitonin (PCT)

  Area under the receiver operating characteristic curve (AUC) of serum Procalcitonin (PCT) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• Diagnostic Accuracy of C-Reactive Protein (CRP)

  Area under the receiver operating characteristic curve (AUC) of serum C-Reactive Protein (CRP) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• Diagnostic Accuracy of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)

  Area under the receiver operating characteristic curve (AUC) of serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• Diagnostic Accuracy of Presepsin

  Area under the receiver operating characteristic curve (AUC) of serum Presepsin concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• Diagnostic Accuracy of Soluble Urokinase Plasminogen Activator Receptor (suPAR)

  Area under the receiver operating characteristic curve (AUC) of serum Soluble Urokinase Plasminogen Activator Receptor (suPAR) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• Diagnostic Accuracy of Interleukin-6 (IL-6)

  Area under the receiver operating characteristic curve (AUC) of serum Interleukin-6 (IL-6) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• Diagnostic Accuracy of Interleukin-8 (IL-8)

  Area under the receiver operating characteristic curve (AUC) of serum Interleukin-8 (IL-8) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• Diagnostic Accuracy of Pro-Adrenomedullin (Pro-ADM)

  Area under the receiver operating characteristic curve (AUC) of serum Pro-Adrenomedullin (Pro-ADM) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value.

  At enrollment (baseline), and at 72 hours after enrollment

• AUC of Combined Multi-Parameter Early-Warning Model

  Area under the receiver operating characteristic curve of a composite model integrating vital signs (temperature, heart rate, respiratory rate, blood pressure, SpO2), laboratory values, and the biomarkers listed above for early warning of infection.

  From 24 hours before to 72 hours after infection onset

• Diagnostic Accuracy of AI-Based Automated Warning System

  Accuracy (%) of a machine-learning-based (random forest, XGBoost, deep learning) automated warning system using electronic medical record data to predict infection onset.

  From 24 hours before to 72 hours after infection onset

• Lead Time of AI-Based Warning System

  Time interval, in hours, between the AI system alert and the subsequent clinical diagnosis of infection.

  Up to 24 hours before clinical diagnosis

• Time to First Effective Antibiotic Administration

  Time, in hours, from infection recognition to administration of the first in vitro active antibiotic.

  Within 6 hours of infection onset

• Rate of Appropriate Empirical Antibiotic Therapy

  Percentage of patients receiving empirical antibiotic therapy subsequently confirmed to be active against the identified pathogen(s).

  90 days after enrollment

• Rate of Antibiotic Coverage of Resistant Organisms

  Percentage of patients with identified multidrug-resistant organisms whose empirical antibiotic regimen provided adequate in vitro coverage.

  90 days after enrollment

• Antibiotic De-escalation Rate

  Percentage of patients whose antibiotic regimen was narrowed (de-escalated) based on culture and susceptibility results.

  90 days after enrollment

• Duration of Antibiotic Therapy

  Number of days of antibiotic treatment administered for the index infection.

  90 days after enrollment

• Time to Source Control

  Time, in hours, from infection recognition to definitive source-control intervention (drainage, debridement, catheter removal, or surgery).

  90 days after enrollment

• Compliance Rate with SSC Bundle Elements

  Percentage of eligible patients/bundle elements for which Surviving Sepsis Campaign bundle elements were completed within the recommended time window.

  90 days after enrollment

Secondary Outcomes (76)

• CD3+ T Lymphocyte Count/Percentage

  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

  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

  At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis

• CD4+/CD8+ Ratio

  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

  At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis

Study Arms (3)

Sepsis

Incident Sepsis-3.0-defined sepsis/septic shock during ICU admission (SOFA score increase ≥ 2 points in the presence of documented infection)

Infection without sepsis

Patients with documented infection, SOFA score \< 2, and absence of organ injury

Other: Not applicable- observational study

Non-infectious severe illness

Patients without evidence of infection admitted to the ICU for non-infectious conditions

Other: Not applicable- observational study

Interventions

Not applicable- observational study OTHER

Not applicable- observational study

Infection without sepsis; Non-infectious severe illness

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the ICU

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Beijing Chao Yang Hospital: lead
• The People's Hospital of Hebei Province: collaborator
• Tianjin First Central Hospital: collaborator
• Second Hospital of Shanxi Medical University: collaborator
• Beijing Obstetrics and Gynecology Hospital: collaborator
• Affiliated Hospital of Hebei University: collaborator
• Hebei Provincial Hospital of Traditional Chinese Medicine: collaborator
• Hangzhou Hospital of Traditional Chinese Medicine: collaborator
• Baoding First Central Hospital: collaborator
• The Hospital of Shunyi District Beijing: collaborator
• Cangzhou Central Hospital: collaborator
• Hengshui People's Hospital: collaborator
• General Hospital of Taiyuan Iron & Steel Company: collaborator
• Changzhi People's Hospital: collaborator
• Jincheng People's Hospital: collaborator
• Xinxiang Central Hospital: collaborator
• Luohe Central Hospital: collaborator
• Inner Mongolia Baogang Hospital: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator

Study Sites (1)

Beijing Chao Yang Hospital

Beijing, 100020, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 16, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: July 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)