Stress Hydrocortisone In Pediatric Septic Shock
SHIPSS
What is the goal of the study?
Every second someone in the world dies from sepsis. Sepsis represents the most common cause of childhood mortality worldwide. In the United States alone 200 cases of pediatric sepsis are diagnosed each day, with an associated hospital mortality rate of 5-10% and health care expenditures now approaching $5 billion annually. Moreover, nearly one-third of children admitted to pediatric intensive care units (PICU) for septic shock have not regained their baseline health-related quality of life one year following the sepsis event. Children with sepsis benefit from early institution of time-sensitive interventions that address sepsis disease pathogenesis and prevent onset, or modulate progression, of organ dysfunction and risk for death. During early resuscitation of the child with septic shock, in addition to antibiotics, volume replacement, and vasoactive-inotropic support, the 2017 AAP/ACCM Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock treatment algorithm advises the practitioner to consider adjunctive hydrocortisone therapy if the patient “is at risk of absolute adrenal insufficiency or adrenal pituitary axis failure”. However, the potential benefits and risks of this guideline recommendation have not been rigorously examined. On the one hand, corticosteroids are inexpensive and have been frequently demonstrated to improve hemodynamic status in children and adults with sepsis. Conversely, this drug class is known to alter transcription of approximately 30% of the human genome. Notably, corticosteroids down regulate most aspects of the immune response, but particularly adaptive immunity. Moreover, multiple descriptive cohort investigations have reported that adjunctive corticosteroids provide no survival benefit to children with sepsis and may in fact be harmful. SHIPSS is a prospective, randomized, double-blinded, placebo-controlled interventional trial examining the potential benefits and risks of adjunctive hydrocortisone prescribed to children with fluid and vasoactive-inotropic refractory septic shock. Up to 722 children will be enrolled at approximately 20 sites in the United States and will be serially evaluated at baseline, PICU discharge, and 28 days and 90 days following study enrollment (randomization). Subjects treated with hydrocortisone versus placebo will be compared for demographics, illness severity, organ dysfunction, resource utilization, occurrence of adverse events plausibly associated with hydrocortisone administration, and patient-centered, clinically meaningful outcomes related to survival, functional status, and health-related quality of life (HRQL). A parallel SHIPSS investigation, employing an equivalent protocol, will be conducted in approximately 10 participating sites in Canada. Adjunctive therapy for recalcitrant septic shock is an approved indication for hydrocortisone in Canada. Approximately 310 children will be enrolled in Canada, for a total enrollment of up to 1032 patients.
Who can participate in the study?
Please contact the study team listed below to learn more.