ABSTRACT
We aim to advance sepsis research and clinical diagnosis by introducing a new redox trapping formulation for
preservation of blood specimens. The new formulation is anticipated: 1) to prevent artifactual oxidation and loss
of specimen integrity during storage, 2) to enable studies of redox metabolism which underlines the dysregulated
immunometabolic response in sepsis, and 3) to improve analysis of differentiating redox molecular markers
associated with demographic features (age, gender and racial ethnicity). Our combined expertise of redox
biochemistry and innovation in patented redox chemical reagents, sepsis mechanisms, trial design and clinical
expertise will be applied first to validate the new redox trapping formulation (R21 Phase) and then to scale-up
by deploying this for collection of blood specimens at sites participating in the EMbedded Precision in Acute Care
Trials (EMPACT) Network (R33 Phase). This is a newly formed network of premier critical care clinical trials sites
designed to conduct precision clinical trials and discovery research in sepsis. Successful accomplishment of our
aims will improve staging of septic patients and clinical precision research for discovery of new therapeutic
targets for treatment of sepsis. More specifically, during the R21 Phase we will investigate the compatibility of
the new redox formulation with high-end mass spectrometry and single cell technologies to evaluate its
performance for measurement of redox and other biomarkers. The new formulation will be compared with current
standard of care procedures for blood collection for clinical and research purposes (gold standard). To further
validate this formula in sepsis patients, we will then evaluate its effects on standard clinical lab tests in a pilot
study using prospectively collected paired single timepoint samples from critically ill patients with sepsis. We will
further determine the advantage of redox trapping formulation by linking the measurements to physiologic and
outcome data collected passively through the Wake Forest Critical Care Data Analytic Platform. Upon
accomplishment of key metrics at the completion of R21 Phase, we will work with the EMPACT Network in the
R33 Phase to collect blood specimens from 150 patients at 3 timepoints across the continuum of their disease
progression using the standard methods and the new redox formulation. Analysis using high-end omics
technologies will produce information-rich and redox-specific datasets, which will be integrated using
bioinformatics approaches and linked to clinical data captured passively via the EMPACT data warehouse to
generate new hypotheses for sepsis research. Lastly, we include a plan to share cryopreserved specimens,
clinical and molecular data with investigators at the institution to support discovery or hypothesis-driven research
through pilot mechanisms under the Center for Redox Biology and Medicine and Critical Illness, Injury and
Research Recovery Research Center directed by MPIs Furdui and Files, respectively, and with outside
investigators via EMPACT.