Clinical trial NCT05311046: Biomarker-enhanced Artificial Intelligence Based Pediatric Sepsis Screening Tool
Official title: Biomarker-enhanced Artificial Intelligence Based Pediatric Sepsis Screening Tool Towards Early Recognition and Personalized Therapeutics
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Sepsis
Keywords: pediatric sepsis
Lead sponsor: Computer Technology Associates, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Children's Hospital Medical Center, Cincinnati
name: Rainbow Babies and Children's Hospital
name: Johns Hopkins University
name: Johns Hopkins All Children's Hospital
name: Emory University
First posted: 2022-04-05
Enrollment: 12961
Sex: ALL
Minimum age (years): 3
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: OTHER
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.

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.

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.).

Eligibility criteria: Inclusion Criteria:

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.

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

Primary outcomes:
measure: Effective Expert System-based Pediatric Sepsis Screening Tool (PSCT)
timeFrame: Final 3 months of study period.
measure: High performance Expert System-based Pediatric Sepsis Screening Tool (PSCT)
timeFrame: Using "early data" following presentation to ED, e.g., upon receipt of biomarker data within 1st 3 hours of presentation)
Secondary outcomes:
measure: Effective sepsis phenotyping for personalized treatment
timeFrame: Features based on 1st 6 hours following presentation in patients diagnosed with sepsis and treatment protocol initiated.
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
Study officials:
affiliation: CTA
name: Carmelo "Tom" E Velez, PhD
role: STUDY_DIRECTOR
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