SHIPSS: Stress Hydrocortisone In Pediatric Septic Shock

Stress Hydrocortisone In Pediatric Septic Shock (SHIPSS) Project Summary
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 40% of children admitted to pediatric intensive care units (PICUs) for septic
shock have not regained their baseline health-related quality of life one year following the sepsis
event.
During early resuscitation of the child with septic shock, in addition to antibiotics, volume
replacement, and vasoactive-inotropic support, the most recent pediatric treatment guidelines
advise 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 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,
recent data suggests that children with particular gene expression profiles in sepsis have
increased likelihood of mortality when treated with corticosteroids.
SHIPSS (Stress Hydrocortisone In Pediatric Septic Shock) is a prospective, randomized,
double-blinded, placebo-controlled trial examining the potential benefits and risks of adjunctive
hydrocortisone prescribed to critically ill children with fluid and vasoactive-inotropic refractory
septic shock. Up to 1,032 children will be enrolled, randomized, and evaluated at baseline,
PICU discharge, and 28 and 90 days following study enrollment/randomization.
The primary hypothesis is that hydrocortisone, compared to placebo, will decrease the
proportion of subjects with poor outcomes, defined as death or severely impaired (≥25%
decrease from baseline) health-related quality of life. We will also follow subjects to detect side
effects of the treatment. Finally, we will test the hypothesis that biomarker-based prognostic and
predictive enrichment strategies can improve our ability to identify which children with septic
shock are more likely to benefit from adjunctive hydrocortisone, and which may be harmed. This
randomized control trial will have a significant impact on public health by providing the
heretofore missing evidence to inform guidelines regarding therapy for septic shock in children.

Grant Number: 5R01HD096901-05
NIH Institute/Center: NIH
Principal Investigator: MICHAEL AGUS