Biomarker-enhanced Artificial Intelligence Based Pediatric Sepsis Screening Tool

NCT05311046 | Not Yet Recruiting DMC

• 1 other identifier: NIAID 1R41AI167224-01
• Study Type: observational
• Target: 12,961
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this proposed research is the derivation of a biomarker-enhanced artificial intelligence (AI)-based pediatric sepsis screening tool (PSCT) (software) that can be used in combination with the hospital's electronic health record (EHR) system to monitor and assess real-time emergency department (ED) electronic health record (EHR) data towards the enhancement of early pediatric sepsis recognition and the initiation of timely, aggressive personalized sepsis therapy known to improve patient outcomes. It is hypothesized that the screening performance (e.g., positive predictive value) of the envisioned screening tool will be significantly enhanced by the inclusion of a biomarker panel test results (PERSEVERE) that have been shown to be effective in prediction of clinical deterioration in non-critically ill immunocompromised pediatric patients evaluated for infection. It is also hypothesized that enhanced phenotypes can be derived by clustering PERSEVERE biomarkers combined with routinely collected EHR data towards improved personalized medicine.

Conditions

Sepsis

Keywords

pediatric sepsis

Outcome Measures

Primary Outcomes (2)

• Effective Expert System-based Pediatric Sepsis Screening Tool (PSCT)

  Over a usability test period, by emulation of the logic of experts in a screening tool that cam be continuously improved with experience, achieve a high level of ED workflow usability towards improved early recognition of IPSO sepsis, as perceived by practicing ED clinicians engaged in usability testing.

  Final 3 months of study period.

• High performance Expert System-based Pediatric Sepsis Screening Tool (PSCT)

  To derive a high performing (e.g., sensitivity/specificity \> 90%, PPV \> 40%) PSCT to identify patients in the ED meeting IPSO sepsis criteria using early encounter data (e.g. upon receipt of biomarker data within 1st 1-3 hours of presentation).

  Using "early data" following presentation to ED, e.g., upon receipt of biomarker data within 1st 3 hours of presentation)

Secondary Outcomes (1)

• Effective sepsis phenotyping for personalized treatment

  Features based on 1st 6 hours following presentation in patients diagnosed with sepsis and treatment protocol initiated.

Study Arms (2)

Retrospective EHR-data only group

Members of this group are pediatric patients between the ages of 3 months to 45 years inclusive, that presented to one of the six participating institution's emergency department between the years 2016-2021 and screened positive for suspicion of sepsis using the institution's existing pediatric sepsis screening protocol and receive a blood culture order. Current pediatric screening/alerting tools are known to be highly sensitive but poorly specific. "Cases" in this cohort will be comprised of those that are ultimately diagnosed with sepsis and/or receive protocolized sepsis treatment. "Controls" in this cohort will be those with a false positive alert, i.e., are not diagnosed with sepsis and do not receive protocolized sepsis treatment.

Diagnostic Test: Pediatric sepsis screening tool (either algorithmic or manual)

Prospective EHR and Biomarker data group

Members of this group are pediatric patients between the ages of 3 months to 45 years inclusive, that presented to one of the six participating institution's emergency department during the study enrollment period, screen positive for suspicion of sepsis using the institution's existing pediatric sepsis screening protocol, receive a blood culture order and provide informed consent/assent for the collection of a 1-5 mL blood sample to be used to measure PERSEVERE biomarkers. Members of this cohort will have also consented to the reuse of their medical record data for the research. Current pediatric screening/alerting tools are known to be highly sensitive but poorly specific. "Cases" in this cohort will be comprised of those that are ultimately diagnosed with sepsis and/or receive protocolized sepsis treatment. "Controls" in this cohort will be those with a false positive alert, i.e., are not diagnosed with sepsis and do not receive protocolized sepsis treatment.

Diagnostic Test: Pediatric sepsis screening tool (either algorithmic or manual)

Interventions

Pediatric sepsis screening tool (either algorithmic or manual) DIAGNOSTIC_TEST

All participating institutions employ either an algorithmic, manual, or combined algorithmic/manual pediatric sepsis screening protocol for patients that present with fever and/or a concern for infection. While the specific parameters tested in screening tools differ, they generally consist of tests for a systemic inflammatory response (e.g. SIRS) and/or organ dysfunction (e.g. SOFA) and/or high susceptibility (e.g. immunocompromised) factors.

Prospective EHR and Biomarker data group; Retrospective EHR-data only group

Eligibility Criteria

• Age: 3 Months - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Those pediatric patients presenting to the emergency department with a fever and/or concern for infection and screen positive for pediatric sepsis based on existing institutional screening protocol.

You may qualify if:

• Patients 3 months -45 years of age, inclusive
• Diagnosed with sepsis by a clinician or trigger a sepsis alert and a blood culture is ordered. Controls will be false positive patients.
• For those patients that will be prospectively enrolled for blood sample collection: will require a venipuncture or intravenous line placement.

You may not qualify if:

• Patients participating in an investigational program with interventions outside of routine clinical practice
• Patients with parents or LARs that don't speak English or Spanish
• Pregnancy

Sponsors & Collaborators

• Computer Technology Associates, Inc.: lead
• Children's Hospital Medical Center, Cincinnati: collaborator
• Rainbow Babies and Children's Hospital: collaborator
• Johns Hopkins University: collaborator
• George Washington University: collaborator
• All Children's Research Institute: collaborator

Study Sites (1)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (42)

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Related Links

• "Introduction to Classification \& Regression Trees (CART) - Data Science Central."
• "Plan-Do-Study-Act (PDSA) Worksheet \| IHI - Institute for Healthcare Improvement."
• "OMOP Common Data Model - OHDSI."

Biospecimen

Retention: SAMPLES WITHOUT DNA

For each consenting patient a plasma will be collected within the first 6 hours of triage.

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

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

Study Officials

• Carmelo "Tom" E Velez, PhD

  CTA

  STUDY DIRECTOR

Central Study Contacts

Ioannis Koutroulis, MD

CONTACT

202-476-4177; IKOUTROULI@childrensnational.org

Carmelo "Tom" E Velez, PhD

CONTACT

19495005883; tom.velez@cta.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics, Emergency Medicine, Genomics and Precision Medicine

Study Record Dates

• First Submitted: March 20, 2022
• First Posted: April 5, 2022
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

US (1)