Clinical Outcomes Using Molecular Prediction in Acute Suspected Sepsis and Infection

The investigators are studying a novel and contemporary paradigm for the management of critically ill patients using molecular (RNA)-based biomarkers to predict clinical deterioration in patients with suspected sepsis.

Building on a successful collaboration with the National Research Council of Canada (NRC), supported by NRC Pandemic Research Challenge Program, by a Natural Sciences and Engineering Research Council of Canada (NSERC) and Canadian Institute of Health Research (CIHR) collaborative grant (CHRP) and Project Grant, our team has developed an RNA-based classifier composed of 4 genes and 2 house-keeping genes (SEPSET) that together, predict the likelihood of clinical deterioration.

In this study, the investigators will prospectively evaluate, compare and combine assessment of the predictive capability of SEPSET, clinical, and laboratory measures to identify patients with suspected sepsis at increased risk for future deterioration, as defined by any of the following: intensive care unit (ICU) admission, initiation of respiratory support (non-invasive ventilatory support), endotracheal intubation, administration of vasopressors/inotropes, or death within the first 72 hours of presentation. Results from SEPSET will be correlated with clinical trajectories evaluated across key clinically relevant endpoints: ventilator liberation, ventilator-free days, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and death at 28-days and 90-days.

Primary outcomes

• Percent accuracy of the SEPSET 6 gene classifier to predict clinical deterioration when compared to documented clinical deterioration in patients medical charts [2 years]: Prospective evaluation, comparison, and combinatorial predictive capability of the SEPSET classifier, clinical, and laboratory measures within 24h of presentation, to identify patients with suspected sepsis at increased risk for future deterioration: as defined by any of the following: ICU admission, initiation of respiratory support (mechanical ventilation - non-invasive), endotracheal intubation, administration of vasopressors/inotropes, or death within the first 72h of presentation. The investigators will perform RNA sequencing of 6 genes that have been found to be able to predict clinical deterioration when combined. The likelihood of clinical deterioration determined by using this set of genes will then be compared to actual rates of clinical deterioration based on documented information in the patients medical chart such as need for various types of organ support.

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Adult patients 18 years of age or older
* Suspicion of infection - as defined by:
* Physician documentation of suspected infection. OR
* Initiation of a sepsis-related diagnostic or treatment pathway within 24 hours of presentation

OR

* EPIC - ALERT System Identifies patient as risk for Sepsis AND
* Lactate ≥3 OR pH ≤7.35 and at least 2 of the following SIRS Criteria that cannot be explained by another diagnosis:
* Temperature >38.3°C or <35°C
* Heart Rate >110 bpm
* Respiratory Rate >25 or PaCO2 <32 mmHg
* WBC >12,000 mm3, <4000 mm3, or 10% immature (band) forms

Exclusion Criteria:

* Patients with Do Not Resuscitate and Do Not Intubate orders
* EAA Sub-Study: Patients with Leukopenia (leukocyte count <500 cells/mm3) will be excluded. These patients can still be enrolled in the trial.

• https://doi.org/10.1038/s41467-025-59227-x

• Claudia dos Santos, MD, Principal investigator, Unity Health Toronto