Stress Hydrocortisone in Pediatric Septic Shock: Protocol for a Pragmatic, Multicenter, International, Randomized, Double-Blinded, Placebo-Controlled Interventional Trial

OBJECTIVES: Septic shock accounts for approximately 8% of PICU admissions worldwide, carries significant morbidity, and has a reported mortality rate between 5% and 50% depending upon the geographic region in which it occurs. The high morbidity and mortality of this condition have led clinicians to consider corticosteroids when usual management does not achieve hemodynamic stability. However, the evidence for or against the use of corticosteroids in pediatric septic shock is currently unclear. DESIGN: Pragmatic, multicenter, international, randomized, double-blinded, placebo-controlled interventional trial (ClinicalTrials.gov, NCT03401398). SETTING: Approximately 50 PICUs from 11 countries in North America, South America and Asia. PATIENTS: Up to 500 eligible pediatric patients aged one month to 17 years and 8 months with septic shock. INTERVENTIONS: Patients randomized to the hydrocortisone arm receive an initial bolus of 2 mg/kg IV hydrocortisone, followed by 1 mg/kg every six hours until all vasoactive-inotropic infusions have been discontinued for at least 12 h or for a maximum of 7 days. Patients randomized to the placebo arm receive an equivalent volume of normal saline with the identical dosing schedule. MEASUREMENTS AND MAIN RESULTS: The primary outcome is the frequency of new or progressive multiple-organ dysfunction syndrome up to 28 days following enrollment, death or discharge, whichever comes first. The secondary outcome is a composite of the frequency of death or greater than or equal to 25% decrease in health-related quality of life from baseline, assessed at 28 days. CONCLUSIONS: The current Pediatric Surviving Sepsis Guidelines do not provide definitive recommendations regarding the use of corticosteroids in pediatric septic shock. Our study will be the first pediatric trial that is adequately powered to assess both potential benefits and adverse effects of corticosteroids in patients with septic shock. The results of this study will provide definitive data upon which to base future recommendations for corticosteroid administration in pediatric septic shock.