Cincinnati Children’s Hospital Investigators Develop PERSEVERE to Predict Mortality Levels from Sepsis

Nov 19, 2019 | Assay, Biomarker, Cincinnati Children’s Hospital Medical Center, Precision Medicine, Sepsis

Cincinnati Children’s Hospital Investigators Develop PERSEVERE to Predict Mortality Levels from Sepsis

Cincinnati Children’s Hospital Medical Center investigators have developed a new rapid blood assay that can predict mortality risk levels from sepsis and could help inform precision medicine to treat the infections. They have filed patents through the institution’s Innovation Ventures and plan more clinical research and potential commercialization.

The Study

Published in Science Translational Medicine, the researchers included blood samples in the study from 461 children with septic shock along with mouse models with the Pediatric Sepsis Biomarker Risk Model, known as PERSEVERE, a new assay that measures 5 biomarkers for sepsis. This study offered proof of principle for the use of PERSEVERE to guide precision treatment of sepsis

The study focused on prospective testing in an independent cohort, enabling investigators from Cincinnati Children’s Hospital Medical Center to assess the generalizability and reliability of this new tool. The selected cohort included heterogeneity of age, comorbidities and causative pathogen. By shedding light on the underlying biological mechanisms of sepsis, the PERSERVERE tool may help investigators develop new targeted therapeutic treatments.

A Dangerous Situation: Sepsis

Sepsis usually strikes fragile young children and the elderly hospitalized in intensive care units. The complication kills more than 200,000 annually and costs the healthcare system billions of dollars according to the National Institutes of Health (NIH). In this current study 13% of the patients did not survive, but PERSEVERE-based stratification effectively stratified the patients into three risk categories with widely different mortality rates. Moving forward Dr. Wong and team must figure out how to push those survival curves significantly higher among the higher risk patients.

Sepsis is known for its considerable clinical and biological heterogeneity with the causes and outcomes greatly varying between different patients.  PERSEVERE is designed to leverage today’s enhanced genetic and biological analysis technologies to make that variability more manageable. The researchers found that those patients that were measured for higher risk of mortality from sepsis had higher bacterial loads in their blood.

Narrowing down Septic Biomarkers

After more than a decade of research, investigators narrowed down the biomarkers in the assay from 80 to 5 that were able to accurately predict which patients would develop severe cases of sepsis. The 5 biomarkers are C-C chemokine ligand 3 (CCL3), interleukin 8 (IL8), heat shock protein 70 kDa 1B (HSPA1B), granzyme B (GZMB), and matrix metallopeptidase 8 (MMP8). Investigators further refined the tool and added platelet counts as a predictor variable.

Cincinnati Investigator Comments

Hector Wong, MD director of critical care medicine at Cincinnati Children’s Hospital Medical Center said in a new release “The PERSEVERE platform focuses on stratification and prognostication, not diagnostics.” He continued, “Prognostic enrichment is a fundamental tool for precision medicine. It allows us to predict the disease course and progression in individuals and tailor treatment to different groups of patients and individuals.”

Cincinnati Children’s Innovation Ventures Files a Patent: Clinical Trials & Commercialization

The Research team, led by Wong and Lindsell, have secure patents for the PERSEVERE platform through the Cincinnati Children’s technology commercialization group known as Innovation Ventures. They are developing an adult version of PERSEVERE as well as concurrently test the platform as they conclude an NIH-funded clinical trial to use corticosteroids to treat sepsis.

Study Funding

The study was funded by the National Institutes of Health

Lead Research/Investigator

Hector Wong, MD, director of critical care medicine at Cincinnati Children’s Hospital Medical Center

Call to Action: Wong and team will continue to test and refine PERSEVERE and study the biological clues it has uncovered so far to pinpoint onset molecular basis for sepsis and find new treatments. Interested? TrialSite News tracks any developments. Sign up for the Daily Digest.

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