Biomarker-enhanced Artificial Intelligence Based Pediatric Sepsis Screening Tool

February 6, 2023 updated by: Ioannis Koutroulis, Computer Technology Associates, Inc.

Biomarker-enhanced Artificial Intelligence Based Pediatric Sepsis Screening Tool Towards Early Recognition and Personalized Therapeutics

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background and Rationale Existing automated pediatric sepsis screening tools (PSCT) based on consensus criteria currently used in emergency departments do not improve early recognition and/or inform personalized therapeutic decisions leading to improved outcomes. The Improving Pediatric Sepsis Outcomes (IPSO) initiative found that by including patients that receive treatment, the extended criteria captured not only patients who developed sepsis with organ dysfunction (OD), but also those in whom early sepsis was treated with OD potentially averted.

The objective of the proposed effort is to derive and retrospectively validate a biomarker-enhanced AI-based pediatric sepsis screening tool that can be used to screen ED EHR data to improve early recognition, severity stratification, and the timely initiation of personalized sepsis therapy. CTA and its 6 institutional partners jointly propose to establish two de-identified patient registries: 1) the "EHR-data only cohort" (N = 2000) and 2) the "EHR + biomarker data cohort" (N = 400) in support of this objective.

Encounter data elements to be abstracted from EHRs for inclusion in these registries include both structured (e.g., time-stamped physiological measurements, treatments, procedures, outcomes) as well as free text notes.

Data Analysis and biases All study data, including physiological data extracted from patient EHR and results of biomarker assays will be analyzed using a variety of machine learning algorithms and techniques towards producing a high precision sepsis screening predictive model. Analytic methods involve standard descriptive statistical analysis of predictive classification performance (e.g., AUC, sensitivity/specificity, PPV, etc.).

Study Type

Observational

Enrollment (Anticipated)

2400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Recruiting
        • Children's National Hospital
        • Contact:
          • Ioannis Koutroulis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

Inclusion Criteria:

Patients 3 months -17 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Retrospective EHR-data only group
Members of this group are pediatric patients between the ages of 3 months to 17 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)
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
Members of this group are pediatric patients between the ages of 3 months to 17 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)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effective Expert System-based Pediatric Sepsis Screening Tool (PSCT)
Time Frame: Final 3 months of study period.
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)
Time Frame: Using "early data" following presentation to ED, e.g., upon receipt of biomarker data within 1st 3 hours of presentation)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effective sepsis phenotyping for personalized treatment
Time Frame: Features based on 1st 6 hours following presentation in patients diagnosed with sepsis and treatment protocol initiated.
To show that combined PERSEVERE biomarker and EHR data as clustering features (e.g. using latent class analysis) enhances the detection of clinically useful prognostic phenotypes.
Features based on 1st 6 hours following presentation in patients diagnosed with sepsis and treatment protocol initiated.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Computer Technology Associates, Inc.

Collaborators

Johns Hopkins University
Emory University
Children's Hospital Medical Center, Cincinnati
Johns Hopkins All Children's Hospital
Rainbow Babies and Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 9, 2023

Primary Completion (ANTICIPATED)

February 1, 2024

Study Completion (ANTICIPATED)

June 1, 2024

Study Registration Dates

First Submitted

March 20, 2022

First Submitted That Met QC Criteria

March 31, 2022

First Posted (ACTUAL)

April 5, 2022

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 6, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIAID 1R41AI167224-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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