Primary Outcome Measures in Pediatric Septic Shock Trials

OBJECTIVE: To evaluate all published pediatric randomized controlled trials of patients with septic shock from any cause to examine the outcome measures used, the strengths and limitations of these measurements and whether the trial outcomes met feasibility criteria. DATA SOURCES: We used a previously published database of pediatric critical care randomized controlled trials (PICUtrials.net) derived from searches of MEDLINE, EMBASE, LILACS, and CENTRAL. STUDY SELECTION: We included randomized controlled trials of interventions to children admitted to a PICU with septic or dengue hemorrhagic shock which were published in English. DATA EXTRACTION: Study characteristics and outcomes were retrieved by two independent reviewers with disagreement being resolved by a third reviewer. We defined feasibility as 1) recruitment of at least 90% of the targeted sample size and agreement of the observed outcome rate in the control group with the rate used for the sample size calculation to within 10% or 2) finding of a statistically significant difference in an interim or final analysis. DATA SYNTHESIS: Nineteen of 321 identified articles were selected for review. Fourteen of 19 studies (74%) provided an a priori definition of their primary outcome measure in their "Methods section." Mortality rate was the most commonly reported primary outcome (8/14; 57%), followed by duration of shock (4/14; 29%) followed by organ failure (1/14; 7%). Only three of 19 included trials met feasibility criteria. CONCLUSIONS: Our review found that use of mortality alone as a primary outcome in pediatric septic shock trials was associated with significant limitations and that long-term patient-centered outcomes were not used in this setting. Composite outcomes incorporating mortality and long-term outcomes should be explored for use in future pediatric septic shock trials.