Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shock

Rationale Interventional clinical trials involving children with septic shock would benefit from an efficient preenrollment stratification strategy. Objectives: To test the predictive value of interleukin (IL)-8 for 28-day mortality in pediatric septic shock. Methods: A training data set (n = 40) identified a serum IL-8 of greater than 220 pg/ml as having a 75% sensitivity and specificity for predicting 28-day mortality. This cutoff was then subjected to a series of validation steps. Measurements and Main Results: Subjects were drawn from two large, independent pediatric septic shock databases. Prospective application of the IL-8 cutoff to validation data set 1 (n = 139) demonstrated 78% sensitivity and 64% specificity for 28-day mortality. A serum IL-8 level of 220 pg/ml or less, however, had a negative predictive value for 28-day mortality of 95% in validation data set 1, which was subsequently applied to an independently generated data set of children with septic shock (validation set 2, In = 193). A serum IL-8 level of 220 pg/ml or less had a negative predictive value for 28-day mortality of 94% when applied to validation set 2. Conclusions: A serum IL-8 level of 220 pg/ml or less, obtained within 24 hours of admission, predicts a high likelihood of survival in children with septic shock. We propose that IL-8 can be used to exclude such patients from interventional clinical trials and ultimately derive a study population with a more favorable risk to benefit ratio when subjected to a study agent.