Early Identification and Effective Management of Pediatric Sepsis

Integration of Metabolic and Inflammatory Mediator Profiles as a Potential Diagnostic Approach for Severe Sepsis in PICU

In patients diagnosed as sepsis on PICU admission, early and accurate identification of patients who will develop organ dysfunction (severe sepsis) is critical for effective management and positive outcome. A multiple marker approach would improve clinical utility compared with use of a single marker. The primary goal of this part of study is to define a combination of multiple markers, derived from novel biomarkers (nCD-64, IL-27, sTREM, HLA-DR, IL-10), metabolomics and routine clinical parameters, which could predict severe sepsis and determine the severity of disease.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Severe Sepsis

Detailed Description

We intend to enroll pediatric sepsis patients at four PICUs and divide them into two groups based on clinical outcomes: severe sepsis group (patients who progress into severe sepsis), sepsis group (patients who do not progress in to severe sepsis). We intend to perform predictive modeling using multivariable analyses of the novel biomarkers and derive a biomarker panel and algorithm for early diagnosis of severe sepsis. The predictive value of the biomarker panel for early identification of severe sepsis will be compared with established indices, such as PRISM III and pSOFA score.

• Study Type: Observational
• Enrollment (Actual): 175

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Children's Hospital of Fudan University
    • Shanghai, Shanghai, China
      • Children's Hospital of Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Children's Medical Center
    • Shanghai, Shanghai, China
      • Xinhua Hospital Affiliated to Shanghai Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with sepsis from four tertiary PICUs in Shanghai

Description

Inclusion Criteria:

• The presence of at least two of the following four criteria, one of which must be abnormal temperature or leukocyte count:

  • Coreb temperature of >38.5°C or <36°C.
  • Tachycardia, defined as a mean heart rate >2 SD above normal for age in the absence of external stimulus, chronic drugs, or painful stimuli; or otherwise unexplained persistent elevation over a 0.5- to 4-hr time period OR for children <1 yr old: bradycardia, defined as a mean heart rate <10th percentile for age in the absence of external vagal stimulus, β-blocker drugs, or congenital heart disease; or otherwise unexplained persistent depression over a 0.5-hr time period.
  • Mean respiratory rate >2 SD above normal for age or mechanical ventilation for an acute process not related to underlying neuromuscular disease or the receipt of general anesthesia.
  • Leukocyte count elevated or depressed for age (not secondary to chemotherapy-induced leukopenia) or >10% immature neutrophils
• A suspected or proven (by positive culture, tissue stain, or polymerase chain reaction test) infection caused by any pathogen OR a clinical syndrome associated with a high probability of infection. Evidence of infection includes positive findings on clinical exam, imaging, or laboratory tests

Exclusion Criteria:

• patients without informed consent
• discharge within 48 hours

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
severe sepsis; patients who diagnosed as sepsis upon PICU admission and develop organ dysfunction during PICU stay
sepsis; patients recover from sepsis without developing into organ dysfunction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe sepsis	Sepsis plus one of the following: cardiovascular organ dysfunction OR acute respiratory distress syndrome OR two or more other organ dysfunctions	28 day
Death	death	28 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
secondary infection	infection acquired 48h after PICU admission	28 day
length of ICU stay	from PICU admission to discharge	28 day

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: Shanghai Children's Hospital; Shanghai Children's Medical Center; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Guoping Lu, MD, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: June 21, 2019
• First Submitted That Met QC Criteria: June 21, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: biomarkers; predictive model; metabolomics; MODS; inflammatory mediator profile
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: fdpicu-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No