Primary Outcome Measures in Pediatric Septic Shock Trials: A Systematic Review*

Abstract

Objective To evaluate all published pediatric randomized controlled trials (RCTs) 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 source We used a previously published database of pediatric critical care RCTs (PICUtrials.net) derived from searches of MEDLINE, EMBASE, LILACS and CENTRAL. Study selection We included RCTs of interventions to children admitted to a pediatric intensive care unit (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 3 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 utilized in this setting. Composite outcomes incorporating mortality and long-term outcomes should be explored for use in future pediatric septic shock trials.

Core outcome set in paediatric sepsis in low- and middle-income countries: a study protocol

“…Mortality was the most frequent primary outcome while long-term patient-centred outcomes were rarely used. 4 Systematic review A systematic review will be performed to identify both morbidity and mortality outcomes reported in existing studies involving paediatric sepsis in low-and middleincome countries.…”

“…7 8 A systematic review into primary outcome measures in paediatric septic shock trials demonstrated that the use of mortality alone had significant limitations and suggested more long-term outcomes should be explored. 4 A standardised way to evaluate trial outcomes is therefore imperative.…”

Clinical Trials in Pediatric Sepsis: What’s the (End) Point?*

“…Duration of shock and organ dysfunction are two surrogate endpoints that were commonly utilized in the review by Menon et al (5). Although both of these surrogates are associated with mortality in sepsis, it is less clear if reducing duration of shock or organ dysfunction will translate into fewer deaths (11, 12).…”

“…In this issue of Pediatric Critical Care Medicine , Menon et al reviewed endpoints used in randomized trials of pediatric septic shock (including Dengue shock) conducted in a pediatric intensive care unit (PICU) and published between 1986 and 2016 in English-language journals (5). The authors determined if primary endpoints met a “feasibility” metric, which they defined as 1) recruitment of at least 90% of the targeted sample size and agreement of the predicted-to-observed outcome rate to within 10% in the control group or 2) finding a statistically significant difference in the primary outcome.…”

To Evaluate the Effectiveness of Central Venous Pressure Measurement and Inferior Vena Cava Collapsibility Index in Predicting Fluid Responsiveness in Cases of Paediatric Shock

“…Shock in paediatric population is a major problem associated with high mortality and organ failure. 1,2,3 Aggressive and early fluid boluses is the initial treatment of choice. 4,5 Determining intravascular volume status and fluid responsiveness based on clinical examination is challenging.…”