Stress Hydrocortisone In Pediatric Septic Shock
SHIPSS
2 other identifiers
interventional
500
10 countries
44
Brief 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 incidence of new and progressive organ dysfunction (primary outcome) and proportion of children with poor outcomes, defined as death or severely impaired health-related quality of life (HRQL) (secondary outcome), as assessed at 28 days following study enrollment (randomization).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2019
Longer than P75 for phase_3
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 5, 2018
CompletedFirst Posted
Study publicly available on registry
January 17, 2018
CompletedStudy Start
First participant enrolled
March 11, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
October 30, 2025
May 1, 2025
7.6 years
January 5, 2018
October 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
New or progressive multiple organ dysfunction syndrome as assessed utilizing the Pediatric Logistic Organ Dysfunction (PELOD-2) instrument.
Appearance of new or progression of existing organ dysfunctions according to PELOD-2 definitions. PELOD-2 considers 5 organ dysfunctions (neurological, cardiovascular, renal, respiratory, and hematological) with 10 total variables, with dysfunction scored 0 up to 6 for each organ category. Total minimum/maximal scores are 0/33, with increasing score indicating increasing risk of mortality. Logit (mortality) = -6.61 + 0.47 × PELOD-2 score. Probability of death = 1/(1 + exp \[-logit(mortality)\]). A new organ dysfunction or progression of organ dysfunction is defined as an increase score in any organ category from baseline.
28 days following study enrollment
Secondary Outcomes (1)
28-day hospital mortality or ≥25% decrease from baseline in health-related quality of life (HRQL) assessed utilizing the Pediatric Quality of Life Inventory, (PedsQL)
28 days following study enrollment
Other Outcomes (17)
SHIPSS specified adverse events
28 days following study enrollment
Risk stratification sepsis biomarkers and pediatric sepsis endotype
Enrollment and Day 2
Trichotomous mortality/morbidity outcome
28 and 90 days following study enrollment
- +14 more other outcomes
Study Arms (2)
Treatment
ACTIVE COMPARATORApproximately half of the subjects randomized into SHIPSS will be randomized into the Treatment Group and will receive hydrocortisone sodium succinate according to a predetermined dosing schedule.
Placebo
PLACEBO COMPARATORApproximately half of the subjects randomized into SHIPSS will be randomized into the Placebo Group and will receive equivalent study drug volumes of normal saline.
Interventions
Patients randomized to the hydrocortisone treatment arm will receive an initial bolus of 2 mg/kg IV hydrocortisone, 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 to the intervention (hydrocortisone) arm.
Eligibility Criteria
You may qualify if:
- Age is at least 1 month (with corrected gestational age ≥42 weeks), but less than 17 years and 8 months of age
- A documented focus of infection or a strong suspicion of infection at PICU admission, or for patients who develop septic shock during PICU stay, at the onset of the septic shock event
- 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 \<0.5 x 109 cells per litre 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 or equal to 0.10 mcg/kg/min for \>1 hour.
You may not qualify if:
- 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
- Patient in whom steroids are contraindicated at time of screening (e.g. treatment for systemic fungal infection, cerebral malaria, strongyloides)
- 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 at the time of screening
- Patient documented to be pregnant
- Previous enrollment in the SHIPSS study
- (U.S. sites only) Patient in the custody of US protective services
- Patient being evaluated for brain death
- Vasoactive-inotropic agents prescribed solely for an indication other than septic shock
- Confirmed dengue fever
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (44)
University of Arizona Medical Centre
Tucson, Arizona, 85724, United States
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
UCSF Benioff Children's Hospital - Oakland
Oakland, California, 94609, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Benioff Children's Hospital - San Francisco
San Francisco, California, 94143, United States
Nemours Children's Health
Wilmington, Delaware, 19803, United States
University of Chicago, Comer Children's Hospital
Chicago, Illinois, 60637, United States
The University of Illinois at Chicago/OSF Children's Hospital of Illinois
Peoria, Illinois, 61603, United States
University of Louisville, Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
The Children's Hospital at Oklahoma University Medical Center
Oklahoma City, Oklahoma, 73104, United States
Penn State Milton S. Hershey Children's Hospital
Hershey, Pennsylvania, 17033, United States
Le Bonheur Children's Hospital
Memphis, Tennessee, 38163, United States
Primary Children's Hospital
Salt Lake City, Utah, 84108, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
University of Wisconsin Health/American Family Children's Hospital
Madison, Wisconsin, 53792, United States
Santa Casa de Misericordia Da Bahia
Bahia, Brazil
Hospital Jutta Batista - Rio de Janeiro
Rio de Janeiro, Brazil
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
BC Children's Hospital
Vancouver, British Columbia, V6H 3N1, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
McMaster Children's Hospital
Hamilton, Ontario, L8N 3Z5, Canada
London Health Sciences Centre
London, Ontario, N6A 5W9, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
Centre hospitalier universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Montreal Children's Hospital
Montreal, Quebec, H4A 3J1, Canada
Centre hospitalier de l'Université Laval
Québec, Quebec, G1V 4G2, Canada
Royal University Hospital
Saskatoon, Saskatchewan, S7K 1M6, Canada
Rambam Health Care Campus
Haifa, Israel
Hadassah University Medical Center, Ein Kerem
Jerusalem, Israel
Schneider Children's Medical Center of Israel
Petah Tikva, Israel
Kobe Children's Hospital
Kobe, Japan
Aichi Children's Health and Medical Center
Nagoya, Japan
UKM Specialist Children's Hospital
Kuala Lumpur, Malaysia
University Malaya Medical Centre
Kuala Lumpur, Malaysia
Sarawak General Hospital
Kuching, Malaysia
Shifa International Hospital
Islamabad, Pakistan
Aga Khan University Hospital
Karachi, Pakistan
King Abdullah Specialist Children's Hospital
Riyadh, Saudi Arabia
KK Women's and Children's Hospital
Singapore, Singapore
Vietnam National Children's Hospital
Hanoi, Vietnam
City Children's Hospital
Ho Chi Minh City, Vietnam
Related Publications (3)
Menon K, Agus MSD, O'Hearn K, Coughlin-Wells K, Choong K, Kazzaz Y, Lee JH, McNally D, Atreya MR, Ramsay T, Watson RS, Wypij D, Zimmerman JJ; Stress Hydrocortisone in Pediatric Septic Shock (SHIPSS) Study Investigators, Canadian Critical Care Trials Group, and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Stress Hydrocortisone in Pediatric Septic Shock: Protocol for a Pragmatic, Multicenter, International, Randomized, Double-Blinded, Placebo-Controlled Interventional Trial. Pediatr Crit Care Med. 2026 Jan 1;27(1):102-113. doi: 10.1097/PCC.0000000000003872. Epub 2025 Nov 26.
PMID: 41504575DERIVEDTasker RC. Pediatric Critical Care Medicine: New Directions for 2026, Volume 27. Pediatr Crit Care Med. 2026 Jan 1;27(1):1-2. doi: 10.1097/PCC.0000000000003874. Epub 2026 Jan 8. No abstract available.
PMID: 41504572DERIVEDBasu S, Habet V, Delgado M, Chiu P, Knox D, Thibault E, Shukla A, Harrington E, Bailey V, Lipsitz S, Fu Y, Agus M, Kheir J, Sasaki J, Moynihan K. Adjunctive Corticosteroids for Hypotension in the Pediatric Cardiac ICU: Single-Center Retrospective Study, 2020-2021. Pediatr Crit Care Med. 2025 Jul 1;26(7):e877-e888. doi: 10.1097/PCC.0000000000003757. Epub 2025 May 1.
PMID: 40310269DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- 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
Mihir R Atreya, MD, MPH
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
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- 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.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor of Pediatrics/Anesthesiology, University of Washington School of Medicine
Study Record Dates
First Submitted
January 5, 2018
First Posted
January 17, 2018
Study Start
March 11, 2019
Primary Completion (Estimated)
September 30, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
October 30, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- No later than 3 years after the final 90-day assessment or 2 years after the primary paper has been published, whichever comes first.
- Access Criteria
- Anyone can access NICHD DASH, which is a public website with free access to the scientific research community. All users may browse and view information about studies and data archived in NICHD DASH. Users who are interested in submitting or requesting study data must register for a free account.
Per NIH policy, the SHIPSS investigators will provide a de-identified dataset and all the data-related documentation necessary to utilize the study data (dictionary, calculated variables, and standard operating procedures) to the NIH no later than 3 years after the final 90-day assessment or 2 years after the primary paper has been published, whichever comes first. The investigators will submit this dataset to the NICHD data repository, Data and Specimen Hub (DASH). In addition, final datasets and statistical analyses will be archived.