Spectral Medical Inc., Canada
Debra began her professional career as a Registered Nurse, specializing in the adult critical care area. Shortly thereafter Debra joined the critical care clinical research team at Toronto General Hospital. While there, Debra was the project lead for a multi-national, multi-center clinical trial, the MEDIC study. The data was used for a successful 510k de novo submission to the FDA for the Endotoxin Activity Assay (EAA). It was the first IVD in the field of sepsis. Debra went on to follow the device to its commercial partner, as an employee of Spectral Medical. She was appointed Vice President of Clinical Development in 2011. Debra has led many clinical research projects, including the EUPHRATES and TIGRIS clinical trials for a device to treat patients with endotoxemic septic shock. In December 2021, Debra opted for partial retirement and remains a clinical consultant for Spectral Medical. Debra has lectured many times to medical professionals on the topics of sepsis and clinical trials for sepsis. She has been a co-author of more than 50 articles in peer-reviewed journals and lectured for academic and industry audiences.
The mechanisms of the damaging effects of endotoxin on renal function are complex but, in essence, involve dysregulated inflammation, oxidative stress, microvascular dysfunction and poor clearance of endotoxin burden. In both acute and chronic kidney dysfunction high levels of endotoxin are associated with a higher risk of mortality.
Measurement of endotoxin (lipopolysaccharide) in human whole blood has been difficult, in part due to the fact that the conserved active portion of the lipid A molecule is only amenable to binding by a single ligand. The endotoxin activity assay [EAA], is a bioassay based on neutrophil activation by complement opsonized immune complexes of lipopolysaccharide (LPS) and a high affinity IgM antibody. This assay permits detection of the lipid A epitope of LPS in a rapid whole blood assay format. The EAA is approved for use by Regulatory bodies in many regions including the US, Europe, Asia, and Japan. It can be performed in a unit dose format with result generation in 30 minutes and is suitable for patient triage and selection for anti-endotoxin therapy. The EAA has been used identify endotoxic septic shock (ESS) as a phenotype that is characterized by high endotoxin activity in addition to a high burden of organ failure; including hepatic dysfunction, acute kidney injury, and various forms of endothelial dysfunction. ESS is a subset of sepsis with a 28-day mortality that exceeds 40%.
While many drug development companies seek an endotoxin removal strategy, an alternative is via an extracorporeal hemoperfusion cartridge that selectively removes endotoxin from circulating blood. The PMX cartridge (TORAYMYXIN PMX-20R [adult], and TORAYMYXIN PMX-05R [pediatric]) utilizes the antibiotic polymyxin B, which is bound and immobilized to fibers within a cartridge and administered by veno-venous hemoadsorption. Studies using the EAA to identify patients with ESS and treating with polymyxin B hemoperfusion, have shown to be a safe and effective intervention in patients with acute kidney injury to improve survival.