Hydrocortisone for Pediatric Septic Shock

(SHIPSS Trial)

Recruiting in Palo Alto (17 mi)

+55 other locations

Overseen by Jerry J Zimmerman MD, MD, PhD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Jerry Zimmerman

Must be taking: Vasoactive-inotropic agents

Must not be taking: Systemic corticosteroids, Etomidate, Ketoconazole

Disqualifiers: Pregnancy, Brain death, Dengue, others

Stay on Your Current Meds

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking systemic corticosteroids or certain other medications like etomidate or ketoconazole, you may not be eligible to participate.

What data supports the effectiveness of the drug hydrocortisone for pediatric septic shock?

Research suggests that hydrocortisone may help children with septic shock who do not respond to other treatments, especially if they have low adrenal function, as it is recommended in guidelines for such cases. ^{1 2 3 4 5}

Is hydrocortisone safe for use in humans?

Hydrocortisone has been used in both adults and children with septic shock, but its safety and effectiveness can vary. In adults, some studies show higher mortality rates in those receiving hydrocortisone, though this may be due to their more severe illness. In children, guidelines recommend its use in specific cases, but more research is needed to fully understand its safety. ^{2 3 4 6 7}

How does hydrocortisone differ from other drugs for pediatric septic shock?

Hydrocortisone is unique in treating pediatric septic shock because it is specifically recommended for children who do not respond to other treatments like fluids and vasopressors (medications that raise blood pressure) and may have adrenal insufficiency (when the adrenal glands don't produce enough hormones). It is used in low doses to help stabilize blood pressure and improve survival in these severe cases. ^{2 3 5 6 8}

Research Team

Hector R Wong, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

David Wypij, PhD

Principal Investigator

Boston Children's Hospital, Harvard Medical School

Kusum Menon, MD

Principal Investigator

Children's Hospital of Eastern Ontario

Michael Agus, MD

Principal Investigator

Boston Children's Hospital, Harvard Medical School

Jerry J Zimmerman MD, MD, PhD

Principal Investigator

Seattle Children's Hospital, University of Washington School of Medicine

Eligibility Criteria

This trial is for children aged 1 month to less than 17 years and 8 months with severe septic shock, who have had certain tests done, are on multiple medications to support blood pressure, and show signs of infection. It's not for those treated with specific drugs recently, pregnant, in US protective custody, or with certain diseases like adrenal disorders.

Inclusion Criteria

I am younger than 17 years and 8 months old.

I have been prescribed antibiotics.

I have been given two or more heart medications or high-dose adrenaline infusions for over an hour.

Exclusion Criteria

All inclusion criteria have been present for > 12 hours

Enrolled concurrently in a competing interventional clinical trial (formal assessment to be conducted by SHIPSS Core Committee for each potential competing trial)

I have or might have a condition affecting my hormone glands and may need steroids.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either hydrocortisone or placebo for septic shock management

28 days

Daily monitoring in PICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Assessments at 28 and 90 days post-enrollment

Long-term Follow-up

Evaluation of health-related quality of life and functional status

90 days

Treatment Details

Interventions

• Hydrocortisone (Corticosteroid)

Trial Overview The SHIPSS study is testing if hydrocortisone can help kids with septic shock get better outcomes compared to a normal saline placebo. Kids will be randomly assigned to either the drug or placebo group without knowing which one they're getting.

Participant Groups

Group I: Treatment Active Control 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Jerry Zimmerman

Lead Sponsor

Trials

1

Recruited

500+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Dr. Diana W. Bianchi

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Executive Officer since 2016

MD from Stanford University

Dr. Alison Cernich

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Medical Officer since 2020

PhD in Clinical Psychology from University of Maryland

Canadian Critical Care Trials Group

Collaborator

Trials

32

Recruited

227,000+

Children's Hospital of Eastern Ontario

Collaborator

Trials

134

Recruited

61,000+

Dr. Vera Etches

Children's Hospital of Eastern Ontario

Chief Executive Officer

MD from the University of Western Ontario

Dr. Carrol Pitters

Children's Hospital of Eastern Ontario

Chief Medical Officer since 2010

MD from the University of the West Indies

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Executive Officer

MD, University of Ottawa

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Medical Officer

MD, University of Ottawa

Findings from Research

In a study of 6,693 pediatric patients with severe sepsis, the use of systemic corticosteroids was associated with increased mortality, suggesting that they do not improve outcomes in critically ill infants and children.

Independent predictors of mortality included older age, hematologic-oncologic diagnoses, and the use of steroids, indicating that clinicians should be cautious in using corticosteroids for severe sepsis until further randomized clinical trials are conducted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective cohort study of prognostic factors associated with outcome in pediatric severe sepsis: what is the role of steroids? Markovitz, BP., Goodman, DM., Watson, RS., et al.[2022]

In a study of 70 critically ill children with catecholamine-dependent septic shock, stress dose hydrocortisone therapy was found to correlate more with the severity of illness rather than random serum total cortisol levels, indicating that the therapy may not be beneficial for all patients.

The use of stress dose hydrocortisone was associated with worse outcomes, including higher PICU mortality and longer hospital stays, particularly in children with higher baseline cortisol levels, suggesting that this treatment may need to be reconsidered in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes. Nichols, B., Kubis, S., Hewlett, J., et al.[2019]

In a pilot study involving 38 children with septic shock, low-dose intravenous hydrocortisone showed a trend towards faster shock reversal and reduced need for inotropic support compared to normal saline, although these results were not statistically significant.

The study suggests that while low-dose hydrocortisone may be beneficial in managing pediatric septic shock, further research with a larger sample size is needed to confirm its efficacy, especially considering factors like malnutrition and delayed treatment in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose hydrocortisone in pediatric septic shock: an exploratory study in a third world setting. Valoor, HT., Singhi, S., Jayashree, M.[2022]

In a study of 499 patients with septic shock, hydrocortisone did not significantly improve survival rates compared to placebo, regardless of the patients' response to corticotropin testing.

While hydrocortisone did lead to a quicker reversal of shock symptoms, it was associated with a higher incidence of superinfections, including new cases of sepsis and septic shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrocortisone therapy for patients with septic shock. Sprung, CL., Annane, D., Keh, D., et al.[2022]

In a study of 1,470 patients with vasopressor-dependent septic shock, initiating hydrocortisone treatment within the first 12 hours after shock onset was associated with better outcomes, including more days alive and free from vasopressors.

Delaying hydrocortisone treatment beyond 48 hours was linked to higher ICU mortality, emphasizing the importance of timely intervention in septic shock management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock. Sacha, GL., Chen, AY., Palm, NM., et al.[2023]

In a study of 29 patients with severe burn and septic shock, hydrocortisone treatment significantly increased both systolic and diastolic blood pressure, indicating its efficacy in managing blood pressure in these patients.

Despite the positive response in blood pressure, the mortality rate remained unchanged, suggesting that while hydrocortisone can improve hemodynamics, it may not impact overall survival in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood pressure alterations in burn patients with septic shock under hydro-cortisone treatment. Alinejad, F., Momeni, M., Fatemi, MJ., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

A retrospective cohort study of prognostic factors associated with outcome in pediatric severe sepsis: what is the role of steroids? [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Low-dose hydrocortisone in pediatric septic shock: an exploratory study in a third world setting. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical Utilization of Stress Dose Hydrocortisone in Adult Patients With Septic Shock: A Retrospective Observational Study at a Large Academic Medical Center. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Hydrocortisone therapy for patients with septic shock. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Low-dose hydrocortisone prolongs survival in a lethal sepsis model in adrenalectomized rats. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock. [2023]

8. Iran pubmed.ncbi.nlm.nih.gov

Blood pressure alterations in burn patients with septic shock under hydro-cortisone treatment. [2020]