Stress Hydrocortisone In Pediatric Septic Shock
a study on Septic Shock
SHIPSS is a multi-institutional, prospective, controlled, randomized, double-blinded interventional trial that will examine the potential benefits and risks of adjunctive hydrocortisone prescribed for children with fluid and vasoactive-inotropic refractory septic shock. It is hypothesized that adjunctive hydrocortisone will significantly reduce the proportion of children with poor outcomes, defined as death or severely impaired health-related quality of life (HRQL), as assessed at 28 days following study enrollment (randomization).
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 (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.
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) HRQL. The investigators will also follow subjects to detect side effects of the treatment. Finally, the investigators 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 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.
The SHIPSS trial will enroll patients from Canada and the US. Health Canada approval is not required as hydrocortisone is approved for use in septic shock in children, and this trial meets the criteria of a Phase IV study. In the United States, this trial is considered a Phase III trial as hydrocortisone is approved for use in septic shock but not specifically approved for use in pediatric septic shock.
Septic Shockhydrocortisonerefractory septic shocksepsisnew/progressive MODSmortalityhealth-related quality of lifecorticosteroid adverse eventssepsis biomarkersShockShock, SepticHydrocortisone 17-butyrate 21-propionateHydrocortisone acetateHydrocortisone hemisuccinateHydrocortisone, sodium succinateNormal saline
You can join if…
Open to people ages 1 month to 17 years
A child receiving treatment in a pediatric intensive care unit is eligible for recruitment into SHIPSS if she/he meets all of the following inclusion criteria:
- Age is at least 1 month (with corrected gestational age ≥42 weeks), but less than 17.5 years.
- A focus of infection has been documented or there is a strong suspicion of infection upon admission to the PICU.
- Surveillance cultures (e.g. blood, urine, cerebral spinal fluid, wound) and/or other microbial diagnostic tests have been obtained.
- One or more antimicrobials have been prescribed.
- Core temperature >38.5 C or <36.0 C or leukocytosis or leukopenia (as defined by the local laboratory) or a left-shifted leukocyte differential (>10% immature granulocyte forms) or a neutrophil count of <500 documented at least once within the 24 hours preceding screening
- Treatment with a continuous infusion of vasoactive-inotropic agent(s) to maintain mean or systolic arterial blood pressure above the age-appropriate target set by the treating clinician
- Administration of two or more vasoactive-inotropic agents at any dose or epinephrine or norepinephrine infusion(s) alone at greater than >0.10 mcg/kg/min for >1 hour.
You CAN'T join if...
A child receiving treatment in a pediatric intensive care unit for sepsis is ineligible for enrollment into SHIPSS if she/he meets any of the following exclusion criteria:
- All inclusion criteria have been present for > 12 hours
- Attending physician expects to prescribe systemic corticosteroids for an indication other than septic shock
- Patient has received any doses of systemic corticosteroids during treatment for sepsis
- Enrolled concurrently in a competing interventional clinical trial (formal assessment to be conducted by SHIPSS Core Committee for each potential competing trial).
- Etomidate or ketoconazole treatment within past 48 hours
- Treatment for systemic fungal infection at time of screening
- Documented cerebral malaria at time of screening
- Documented strongyloides at time of screening
- Known or suspected hypothalamic, pituitary or adrenal disease (including patient has received acute or chronic corticosteroid administration and the physician intends to provide corticosteroid for suspected adrenal suppression)
- . Attending physician, PICU care team, or legally recognized guardians not committed to full treatment and resuscitation
- . Patient documented to be pregnant
- . Previous enrollment in the SHIPSS study
- . Primary disease/injury is a thermal burn
- . (U.S. sites only) Patient in the custody of US protective services.
- UCSF Benioff Children's Hospital
not yet accepting patients
- UCSF Benioff Children's Hospital San Francisco
not yet accepting patients
San FranciscoCalifornia94143United States
- accepting new patients
- Start Date
- Completion Date
- Jerry Zimmerman
- Phase 3
- Study Type
- Last Updated
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