A-104 Clinical Validation of the VITROS® Immunodiagnostics Products B·R·A·H·M·S PCT Test Medical Decision Points and Prediction of Cumulative 28-Day All-Cause Mortality

Abstract

Abstract Background Procalcitonin (PCT) is a biomarker for systemic bacterial infection and sepsis and may be used to aid in decision-making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) and/or sepsis. Procalcitonin medical decision points have been established using the B·R·A·H·M·S PCT sensitive KRYPTOR assay. In this study, we compared the performance of the VITROS® Immunodiagnostic Products B·R·A·H·M·S PCT assay to the performance of the B·R·A·H·M·S PCT sensitive KRYPTOR assay at the established medical decision points. Percent change in PCT level over time can be used to aid in the prediction of cumulative 28-day mortality in patients diagnosed with severe sepsis and septic shock. The 28-day all-cause mortality prediction of the VITROS B·R·A·H·M·S PCT assay was also evaluated in the study. Methods Patient sample sets from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) study conducted in 13 sites in the United States were used in this study. Blood samples were collected on Days 0, 1, 3 and 4 from subjects who were admitted to the ICU with severe sepsis or septic shock. Each patient’s vital status was verified at Day 28. The samples were tested on the VITROS B·R·A·H·M·S PCT assay and the B·R·A·H·M·S PCT sensitive KRYPTOR assay. Concordance analysis between the VITROS B·R·A·H·M·S PCT and the B·R·A·H·M·S PCT sensitive KRYPTOR assays was performed at the established clinical decision points of 0.100 ng/mL, 0.250 ng/mL, 0.500 ng/mL, 2.00 ng/mL and 10.0 ng/mL to determine overall agreement between the two assays. For prediction of cumulative 28-day all-cause mortality using the VITROS B·R·A·H·M·S PCT assay results, the change in PCT values (Δ PCT) from Day 0 to Day 4 and Day 1 to Day 4 was calculated and evaluated against 28-day-all-cause mortality. Results Overall agreements of 98.5%, 98.0%, 97.4%, 97.8% and 98.0% were observed at 0.100 ng/mL, 0.250 ng/mL, 0.500 ng/mL, 2.00 ng/mL and 10.0 ng/mL, respectively, with the B·R·A·H·M·S PCT sensitive KRYPTOR assay. Δ PCT decline >80% or ≤80% was significantly associated with 28-day-all-cause mortality (P = 0.006). Univariate Cox proportional hazards regression analysis showed a 1.93-fold increase in risk for mortality in subjects with a Δ PCT change ≤80%. Conclusion The VITROS B·R·A·H·M·S PCT assay demonstrated excellent agreement with the B·R·A·H·M·S PCT sensitive KRYPTOR assay at medical decision points used to aid in decision-making on antibiotic therapy for patients with suspected or confirmed LRTI and/or sepsis. Clinical performance shows ΔPCT information can be used to classify patients diagnosed with severe sepsis or septic shock as lower and higher risk for cumulative 28-day all-cause mortality.