Summary

for people ages 1 month to 18 years (full criteria)
at Oakland, California and other locations
study started
estimated completion:

Description

Summary

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, as assessed at 28 days following admission to a pediatric intensive care unit for the sepsis event.

Details

Sepsis represents the most common cause of childhood mortality worldwide. In the United States alone, 21,000-42,000 cases of pediatric sepsis occur annually, 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 PICU admission for the septic shock event.

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. 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 RCT will have a significant impact on public health by providing the heretofore missing evidence to inform guidelines regarding therapy for septic shock in children.

Keywords

Septic Shock hydrocortisone refractory septic shock sepsis new/progressive MODS mortality health-related quality of life corticosteroid adverse events sepsis biomarkers Shock Shock, Septic Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Cortisol succinate Hydrocortisone, sodium succinate Normal saline

Eligibility

You can join if…

Open to people ages 1 month to 18 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:

  1. Age is at least 1 month (with corrected gestational age ≥42 weeks), but less than 17.5 years.
  2. A focus of infection has been documented or there is a strong suspicion of infection upon admission to the PICU.
  3. Surveillance cultures (e.g. blood, urine, cerebral spinal fluid, wound) and/or other microbial diagnostic tests have been obtained.
  4. One or more antimicrobials have been prescribed.
  5. Core temperature >38.5 C or <36.0 C or leukocytosis or leukopenia and a left-shifted leukocyte differential with >10% immature granulocyte forms has been documented at least once within the 24 hours preceding screening.
  6. Treatment with a continuous infusion of vasoactive-inotropic agent(s) to maintain age-appropriate mean arterial blood pressure or a mean arterial blood pressure target set by the treating clinician for maintaining perfusion.
  7. 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:

  1. All inclusion criteria have been present for >24 hours.
  2. Attending physician expects to prescribe systemic corticosteroids for an indication other than septic shock (e.g., patient has received acute or chronic corticosteroid administration and the physician intends to provide corticosteroid for suspected adrenal suppression).
  3. Enrolled concurrently in a competing interventional clinical trial (formal assessment to be conducted by CCC for each potential competing trial).
  4. Etomidate or ketoconazole treatment within the previous 48 hours.
  5. Treatment for systemic fungal infections at time of screening.
  6. Documented cerebral malaria at the time of screening.
  7. Documented strongyloides infection at the time of screening.
  8. Attending physician, PICU care team, or legally recognized guardians are not committed to full treatment and resuscitation.
  9. Patient documented to be pregnant.
  10. . Previous enrollment in the SHIPSS study.
  11. . Primary disease/injury is a thermal burn.
  12. . Known disease involving the hypothalamic-pituitary-adrenal axis.
  13. . Patient in the custody of US protective services.

Locations

  • UCSF Benioff Children's Hospital not yet accepting patients
    Oakland California 94609 United States
  • UCSF Benioff Children's Hospital San Francisco not yet accepting patients
    San Francisco California 94143 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Jerry Zimmerman
ID
NCT03401398
Phase
Phase 3
Study Type
Interventional
Last Updated
January 15, 2018