Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
722

Summary

Conditions
Septic Shock
Type
Interventional
Phase
Phase 3
Design
Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: Patients randomized to the hydrocortisone treatment arm will receive an initial bolus of 2 mg/kg IV hydrocortisone (maximum 100 mg), followed by 1 mg/kg (maximum 50 mg) of hydrocortisone dosed every six hours for a maximum of seven days or until all vasoactive infusions have been discontinued for at least 12 hours, whichever comes first. When the hydrocortisone course is completed, the medication will be discontinued. Patients randomized to the placebo treatment arm will receive an equivalent volume of normal saline, with the identical dosing schedule outlined above.Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Subjects, families, critical care providers and investigators will be blinded to study drug administration. Only the local performance site research pharmacist will be un-blinded.Primary Purpose: Treatment

Participation Requirements

Age
Younger than 117 years
Gender
Both males and females

Description

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...

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, 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. Subjects will be monitored daily while receiving care in the PICU for the occurrence of adverse events, including the following protocol specified events:hyperglycemia treated with any insulin; gastrointestinal hemorrhage treated with blood product transfusion or vasopressin or octreotide infusion; delirium requiring medical treatment; and hospital-acquired infection treated with new antimicrobials. 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.

Tracking Information

NCT #
NCT03401398
Collaborators
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Canadian Institutes of Health Research (CIHR)
  • Canadian Critical Care Trials Group
  • Children's Hospital of Eastern Ontario
Investigators
Principal Investigator: Jerry J Zimmerman MD, MD, PhD Seattle Children's Hospital, University of Washington School of Medicine Principal Investigator: Michael Agus, MD Boston Children's Hospital, Harvard Medical School Principal Investigator: Hector R Wong, MD Children's Hospital Medical Center, Cincinnati Principal Investigator: David Wypij, PhD Boston Children's Hospital, Harvard Medical School Principal Investigator: Kusum Menon, MD, MSc Children's Hospital of Eastern Ontario