A Phase 3 interventional study of Hydrocortisone, sodium succinate and Normal saline in Septic Shock, sponsored by Jerry Zimmerman. Recruiting at 44 sites in 10 countries. Open to participants aged 1 Month to 17 Years. Per ClinicalTrials.gov, last updated 2025-10-30.
Sponsored by Jerry Zimmerman · Phase 3, Interventional, and Treatment
Among 20 studies testing hydrocortisone in Shock, Septic — 3 open to participants now, 3 under way, 1 of them phase 3. Hydrocortisone · Shock, Septic.
Among the 20 studies testing hydrocortisone in Shock, Septic, this one is the 3rd largest by planned enrollment, is one of 3 that started in 2019, is one of 7 in phase 3, and was the 12th registered.
1,078 studies on the registry are indexed under Shock, Septic; 232 are open to participants now.
Browse Shock, Septic studies →3 of the 20 studies testing hydrocortisone in Shock, Septic are open now, in 11 countries. Recruiting first, the newest first:
Northern Jiangsu People's Hospital · Sites in China
Ages 18–90
Kingman Regional Medical Center · Sites in United States
Ages 18+
By country, each count listing its studies:
Hydrocortisone: first FDA approval 1951 (HYDROCORTONE), first EMA approval 2011. What it is approved for, and how studies give it, is on its page →
Of the 136 Shock, Septic studies recruiting now, 102 (75%) set no upper age limit and 19 (14%) stop at 75 or younger; 12 take children under 18; 13 take healthy volunteers.
This study: 1 Month to 17 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
20 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 2 2 · Phase 3 8 · Phase 4 7
First in 2002; this study’s year is marked. 3 started in 2019.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 500 is above the median of 79 across 636 interventional studies indexed under Shock, Septic.
Median enrollment 121 across the 20 interventional studies. Of the 17 that completed or were terminated, 4 (24%) have results posted.
This tab as a report to print or save as PDF → With an account.
None of the 20 has an industry lead sponsor. The 10 most frequent:
This is the only study on the registry with Jerry Zimmerman as lead sponsor.
Jerry Zimmerman has 1 study filed under Shock, Septic — fewer than ten, so there is no comparison to draw.
None of the studies under way reaches primary completion within a year.
Among the 20 studies testing hydrocortisone in Shock, Septic, from their registry updates:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
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).
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
Exclusion Criteria:
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:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Hydrocortisone, sodium succinate
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.
Drug: Normal saline
Drug page: Hydrocortisone
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.
Also known as: SOLU-CORTEF- hydrocortisone sodium succinate injection
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.
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.
Time frame: 28 days following study enrollment
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
Time frame: 28 days following study enrollment
SHIPSS specified adverse events
Occurrence of adverse events plausibly associated with corticosteroid administration. SHIPSS specified events include hyperglycemia, gastrointestinal hemorrhage, delirium, and hospital-acquired infection
Time frame: 28 days following study enrollment
Risk stratification sepsis biomarkers and pediatric sepsis endotype
Risk stratification sepsis biomarkers will be measured in serum obtained at enrollment and on Day 2. The PERSEVERE (PEdiatRic SEpsis biomarkEr Risk modEl) will be used to determine the patient's risk of mortality. mRNA will be isolated from blood samples collected at enrollment and on Day 2 to classify the patient as pediatric septic shock Endotype B or A. A composite outcome of sepsis endotype and PERSEVERE risk of mortality will be used to determine if a biomarker-based prognostic model and predictive enrichment strategies allow identification of children with septic shock more likely to benefit from adjunctive hydrocortisone. We hypothesize that pediatric septic shock "endotype B" subjects having an intermediate to high Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-based risk of mortality will derive significant benefit from adjunctive corticosteroids, compared to endotype B subjects having a low risk and endotype A subjects at all risk levels.
Time frame: Enrollment and Day 2
Trichotomous mortality/morbidity outcome
This is a 3-level ordinal endpoint, with levels death, survival with severely impaired HRQL (≥25% decrease from baseline), and survival without severely impaired HRQL, assessed at 28 and 90 days. This approach is similar to that recently reported for assessment of functional status among children encountering critical illness, utilizing the Functional Status Scale. This endpoint is expected to be highly correlated with the primary efficacy endpoint.
Time frame: 28 and 90 days following study enrollment
90-Day Death or ≥25% decrease in HRQL from baseline
Mortality or ≥25% decrease in PedsQL from baseline
Time frame: 90 days following study enrollment
Vasoactive-inotropic infusion-free days through day 28
Vasoactive-inotropic infusion-free days through day 28 is defined as 28 minus duration of vasoactive-inotropic infusions. Subjects who die or are still receiving vasoactive-inotropic infusions by day 28 will be censored at 28 days and assigned zero vasoactive-inotropic infusion-free days.
Time frame: 28 days following study enrollment
Mechanical ventilation-free days through day 28
Mechanical ventilation-free days through day 28 is defined as 28 minus duration of mechanical ventilation. Subjects who die, are still receiving mechanical ventilation, or are transferred from the PICU still receiving mechanical ventilation by day 28 will be censored at 28 days and assigned zero mechanical ventilation-free days.
Time frame: 28 days following study enrollment
Utilization of acute renal replacement therapy (RRT)
Proportion of subjects receiving acute RRT. All types of acute RRT will be considered, including hemodialysis, continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and peritoneal dialysis. RRT in patients on chronic RRT will not be considered.
Time frame: Enrollment to PICU discharge, an average of 2 weeks
Utilization of extracorporeal membrane oxygenation (ECMO)
Proportion of subjects receiving ECMO
Time frame: Enrollment to PICU discharge, an average of 2 weeks
Functional status - POPC
Gross functional status category staging will be made using the Pediatric Overall Performance Category (POPC) score.
Time frame: 28 and 90 days following study enrollment
Functional status - FSS
Functional Status Scale (FSS) will be employed to provide a more granular determination of changes in functional status.
Time frame: 28 and 90 days following study enrollment
PICU-free days through day 28
PICU-free days through day 28 is defined as 28 minus duration of PICU stay. Subjects who die or are still in the PICU by day 28 will be censored at 28 days and assigned zero PICU-free days.
Time frame: 28 days following study enrollment
Hospital-free days through day 28
Hospital-free days through day 28 is defined as 28 minus duration of hospital stay. Subjects who die or are still in the hospital by day 28 will be censored at 28 days and assigned zero hospital-free days through day 28.
Time frame: 28 days following study enrollment
Hospital-free days through day 90
Hospital-free days through day 90 is defined as 90 minus duration of hospital stay. Subjects who die or are still in the hospital by day 90 will be censored at 90 days and assigned zero hospital-free days through day 90.
Time frame: 90 days following study enrollment
Need for new medical devices at hospital discharge
New medical devices prescribed at hospital discharge will be collected from the hospital discharge summary.
Time frame: At time of hospital discharge, expected to be an average of 21 days from time of enrollment
Frequency of primary care, specialty care, and emergency department visits and hospital readmissions
Enumeration of additional health care evaluations following the index hospital admission will occur by telephone survey at 90 days.
Time frame: 90 days following study enrollment
Disruption of family dynamics
The PedsQLTM 2.0 Family Impact Module will be used to quantify the impact of septic shock on family dynamics.
Time frame: Enrollment and 90 days following study enrollment
Cost Analysis - Cost of PICU admission for septic shock
The cost of each patients PICU admission will be determined by summing the cost of the following: PICU and hospital length of stay, frequency of primary care, specialty care, emergency department visits, and hospital readmissions up to 90 days following hospital discharge, new medical devices post hospital discharge and hospital costs of the admission for septic shock.
Time frame: 90 days following study enrollment
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Plan to share: 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, 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.
Started Mar 2019 (actual). Primary completion is estimated for Sep 2026, 90 months after the start.
Of 45 non-industry phase 3 interventional studies under Shock, Septic, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 59. This study's planned 90 months is above that.
Counting every sponsor, half of 46 studies reached it within 42 months; a quarter within 16 and three quarters within 59.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Hydrocortisone