Septic ShockPhase 3SHIPSSNCT03401398
Stress Hydrocortisone In Pediatric Septic Shock
A Phase 3 study testing Hydrocortisone, sodium succinate and Normal saline in people with Septic Shock, run by Jerry Zimmerman at 44 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 17 years
- Conditions the study is for
- Septic Shock
- What is being tested?
- Hydrocortisone, sodium succinate and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 44 sitesin 10 countries
- Study dates
- 11 Mar 2019to 31 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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 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.
Who cannot join
- 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
Show all 16Show fewer
- 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
- Patient admitted directly to the PICU with a thermal burn who has been in the PICU for <72 hours prior to meeting SHIPSS inclusion criteria.
- (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
Trial locations and contacts
44 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
44 sites in 10 countries
United States18 sites, 18 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Michael Agus, MD
- Recruiting
University of Chicago, Comer Children's Hospital
Chicago, Illinois, 60637
Grace Chong, MD
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Ranjit R Chima, MD
- Recruiting
Penn State Milton S. Hershey Children's Hospital
Hershey, Pennsylvania, 17033
Robert Kavanagh, MD
- Recruiting
Saint Barnabas Medical Center
Livingston, New Jersey, 07039
Shira J Gertz, MD
- Recruiting
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Christopher Newth, MD
- Recruiting
University of Louisville, Norton Children's Hospital
Louisville, Kentucky, 40202
John Berkenbosch, MD
- Recruiting
University of Wisconsin Health/American Family Children's Hospital
Madison, Wisconsin, 53792
Pelin Cengiz, MD
- Not yet recruiting
Le Bonheur Children's Hospital
Memphis, Tennessee, 38163
Samir Shah, MD
- Recruiting
UCSF Benioff Children's Hospital - Oakland
Oakland, California, 94609
Natalie Cvijanovich, MD
- Recruiting
The Children's Hospital at Oklahoma University Medical Center
Oklahoma City, Oklahoma, 73104
Christine Allen, MD
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
Adam Schwarz, MD
- Recruiting
The University of Illinois at Chicago/OSF Children's Hospital of Illinois
Peoria, Illinois, 61603
Sandeep Tripath, MD
- Recruiting
Primary Children's Hospital
Salt Lake City, Utah, 84108
Jennifer Workman, MD
- Recruiting
UCSF Benioff Children's Hospital - San Francisco
San Francisco, California, 94143
Patrick McQuillen, MD, McQuillP@ucsf.edu
Matt Zinter, MD, Matt.Zinter@ucsf.edu
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Jerry J Zimmerman, MD, PhD
- Recruiting
University of Arizona Medical Centre
Tucson, Arizona, 85724
Katri Typpo, MD
- Recruiting
Nemours Children's Health
Wilmington, Delaware, 19803
Catherine Madurski, MD
Canada10 sites, 7 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Megan Mahoney, MD
- Recruiting
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Neeraj Verma, MD
- Recruiting
McMaster Children's Hospital
Hamilton, Ontario, L8N 3Z5
Karen Choong, MD
- Recruiting
London Health Sciences Centre
London, Ontario, N6A 5W9
Douglas Fraser, MD
- Recruiting
Centre hospitalier universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Marisa Tucci, MD
- Terminated
Montreal Children's Hospital
Montreal, Quebec, H4A 3J1
- Recruiting
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Kusum Menon, MD, 613-737-7600 ext. 2538, menon@cheo.on.ca
Katie O'Hearn, MSc, 613-737-7600 ext. 4006, kohearn@cheo.on.ca
- Recruiting
Centre hospitalier de l'Université Laval
Québec, Quebec, G1V 4G2
Matthew Weiss, MD
- Terminated
Royal University Hospital
Saskatoon, Saskatchewan, S7K 1M6
- Terminated
BC Children's Hospital
Vancouver, British Columbia, V6H 3N1
Israel3 sites, 3 recruiting
- Not yet recruiting
Rambam Health Care Campus
Haifa
Amir Hadash, MD
- Not yet recruiting
Hadassah University Medical Center, Ein Kerem
Jerusalem
Asaf Mandel, MD
- Not yet recruiting
Schneider Children's Medical Center of Israel
Petah Tikva
Elhanan Nahum, PhD
Malaysia3 sites, 3 recruiting
- Not yet recruiting
UKM Specialist Children's Hospital
Kuala Lumpur
Swee Fong Tang, MD
- Recruiting
University Malaya Medical Centre
Kuala Lumpur
Chin Seng Gan, MD
- Not yet recruiting
Sarawak General Hospital
Kuching
Olive Pei Ee Lee, MD
Brazil2 sites, 2 recruiting
- Recruiting
Santa Casa de Misericordia Da Bahia
Bahia
Rosana Novais de Carvalho, MD, rosana.carvalho@santacasaba.org.br
- Recruiting
Hospital Jutta Batista - Rio de Janeiro
Rio de Janeiro
Arnaldo Prata Barbosa, MD, arnaldo.prata@idor.org
Maria Carvalho Laborne Valle, MD, maria.valle@rededor.com.br
Japan2 sites, 2 recruiting
- Recruiting
Kobe Children's Hospital
Kobe
Hiroshi Kurosawa, MD
- Recruiting
Aichi Children's Health and Medical Center
Nagoya
Takanari Ikeyama, MD
Pakistan2 sites, 2 recruiting
- Recruiting
Shifa International Hospital
Islamabad
Humaira Rafique, MD
Ejaz Ahmed Khan, MD
- Recruiting
Aga Khan University Hospital
Karachi
Qalab Abbas, MD
Vietnam2 sites, 2 recruiting
- Recruiting
Vietnam National Children's Hospital
Hanoi
Phuc Huu Phan, MD
- Not yet recruiting
City Children's Hospital
Ho Chi Minh City
Nam Tran Nguyen, MD
Saudi Arabia1 site, 1 recruiting
- Recruiting
King Abdullah Specialist Children's Hospital
Riyadh
Yasser Kazzaz, MD
Singapore1 site, 1 recruiting
- Recruiting
KK Women's and Children's Hospital
Singapore
Lee Jan Hau, MD
Loh Sin Wee, MD
About this study
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).
Read the detailed 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 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 500 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 the incidence of new or progressive organ dysfunction (primary outcome) and the proportion of subjects with poor outcomes, defined as death or severely impaired (≥25% decrease from baseline) HRQL (secondary outcome). 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 PICUs in Canada, the United States, Saudi Arabia, Israel, Brazil, Vietnam, Pakistan, Japan, Malaysia, and Singapore. 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 not approved for use in pediatric septic shock.
- Conditions
- Septic Shock
- Being tested
- Hydrocortisone, sodium succinate, Normal saline
- Keywords
- hydrocortisone, refractory septic shock, sepsis, new/progressive MODS, mortality, health-related quality of life, corticosteroid adverse events, sepsis biomarkers
- Medical subject headings
- Shock, Septic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrocortisone, sodium succinateDrug
Also called SOLU-CORTEF- hydrocortisone sodium succinate injection
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.
Normal salineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Active comparator | Approximately 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. Receives: Drug: Hydrocortisone, sodium succinate |
| Placebo | Placebo comparator | Approximately half of the subjects randomized into SHIPSS will be randomized into the Placebo Group and will receive equivalent study drug volumes of normal saline. Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Mortality or ≥25% decrease in PedsQL from baseline
Measured: 28 days following study enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start11 Mar 2019
- Primary completion30 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jerry Zimmerman
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor-investigator, Jerry Zimmerman, Seattle Children's Hospital
- Investigators
- Jerry J Zimmerman MD, MD, PhD, Principal investigator, Seattle Children's Hospital, University of Washington School of MedicineMichael Agus, MD, Principal investigator, Boston Children's Hospital, Harvard Medical SchoolMihir R Atreya, MD, MPH, Principal investigator, Children's Hospital Medical Center, CincinnatiDavid Wypij, PhD, Principal investigator, Boston Children's Hospital, Harvard Medical SchoolKusum Menon, MD, MSc, Principal investigator, Children's Hospital of Eastern Ontario
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401398
- Sponsor's protocol ID
- IRB-P00027662
- Other IDs
- 1R01HD096901-01
- Acronym
- SHIPSS
- Status last verified
- May 2025
- First submitted
- 5 Jan 2018
- Last updated
- 30 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 41504575Tasker 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.
PubMed 41504572Basu 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.
PubMed 40310269
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stress Hydrocortisone In Pediatric Septic Shock
- ClinicalTrials.gov ID
- NCT03401398
- Acronym / sponsor ID
- SHIPSS / IRB-P00027662
- Conditions
- Septic Shock
- Keywords
- hydrocortisone, refractory septic shock, sepsis, new/progressive MODS, mortality, health-related quality of life, corticosteroid adverse events, sepsis biomarkers
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Jerry ZimmermanUniversity, hospital or other
- 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
- Study start
- 11 Mar 2019 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 17 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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 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 500 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 the incidence of new or progressive organ dysfunction (primary outcome) and the proportion of subjects with poor outcomes, defined as death or severely impaired (≥25% decrease from baseline) HRQL (secondary outcome). 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 PICUs in Canada, the United States, Saudi Arabia, Israel, Brazil, Vietnam, Pakistan, Japan, Malaysia, and Singapore. 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 not approved for use in pediatric septic shock.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Active comparator | Drug: Hydrocortisone, sodium succinateApproximately 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 comparator | Drug: Normal salineApproximately half of the subjects randomized into SHIPSS will be randomized into the Placebo Group and will receive equivalent study drug volumes of normal saline. |
Who may qualify
- Ages
- 1 month to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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 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
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydrocortisone, sodium succinateAlso: SOLU-CORTEF- hydrocortisone sodium succinate injectionPatients 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. | Drug | Treatment |
| Normal salinePatients randomized to the placebo treatment arm will receive an equivalent volume of normal saline, with the identical dosing schedule to the intervention (hydrocortisone) arm. | Drug | Placebo |
Primary outcome
New or progressive multiple organ dysfunction syndrome as assessed utilizing the Pediatric Logistic Organ Dysfunction (PELOD-2) instrument.
Time frame: 28 days following study enrollment
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.
1 secondary outcome
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)
Time frame: 28 days following study enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2025.
- Derived from this study: PubMed 41504575Menon 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.
- Derived from this study: PubMed 41504572Tasker 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.
- Derived from this study: PubMed 40310269Basu 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.
- Website for SHIPSS investigationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jerry J Zimmerman MD, MD, PhD principal investigator
Seattle Children's Hospital, University of Washington School of Medicine
Michael Agus, MD principal investigator
Boston Children's Hospital, Harvard Medical School
Mihir R Atreya, MD, MPH principal investigator
Children's Hospital Medical Center, Cincinnati
44 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydrocortisone, sodium succinate and Normal saline in people with Septic Shock, run by Jerry Zimmerman at 44 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Canada, Israel, Malaysia, Brazil and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jerry J Zimmerman, MD, PhD (206-987-3862, jerry.zimmerman@seattlechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
New or progressive multiple organ dysfunction syndrome as assessed utilizing the Pediatric Logistic Organ Dysfunction (PELOD-2) instrument. (time frame: 28 days following study enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03401398, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2025.