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Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis - a Randomised Pilot Study (StePS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00732277
Recruitment Status : Completed
First Posted : August 11, 2008
Last Update Posted : May 6, 2016
Imperial College London
St Mary's NHS Trust
University of Bristol
University Hospitals Bristol NHS Foundation Trust
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust

Brief Summary:

Severe bacterial infections affecting multiple body organs, called severe sepsis (including meningococcal sepsis), remain an important cause of death and disability among children. Although early recognition, powerful antibiotics, and good intensive care have improved outcome, we need new ways to further reduce the number of deaths. Research in adults has shown that steroid replacement therapy might be useful. However, children are known to respond differently to adults and a definitive trial in children is needed because of the potentially harmful as well as beneficial effects of steroids.

This pilot study will provide the necessary information to allow the rational design of a large trial conducted at multiple hospitals investigating the role of corticosteroid replacement therapy in childhood sepsis. The study will provide information on how to measure the effects of steroids, information on length of therapy and a better understanding of how steroids work in children. The results emerging from this study will ultimately allow paediatric intensive care clinicians to know whether or not steroids are safe and/or useful.

The primary objective of this open-label study is therefore to gather clinical and laboratory data with which to inform the design of a large phase 3 double blind randomised controlled trial (RCT). The study will provide basic limited safety data, information on length of therapy and an assessment of possible clinical and laboratory endpoints to be used in addition to mortality.

Definition of sepsis:

Presence of a documented infection (eg clinical evidence of pneumonia, skin or soft tissue infection, purpura fulminans, urinary tract infection, abdominal infection) or a diagnostic positive blood culture (community or hospital acquired) within the last 72 hours and at least two of the following, one of which must be abnormal temperature or leucocyte count[3] core temperature of >38.5°C or <36°C; tachycardia (mean heart rate >2 SD above normal for age); mean respiratory rate > 2 SD above normal for age; leucocyte count elevated or depressed for age.

Definition of severe sepsis:

Sepsis plus cardiovascular organ dysfunction (the need for at least 5mcg/kg/min dopamine or dobutamine, or any amount of adrenaline or noradrenaline support), acute respiratory distress syndrome (ARDS), or 2 or more other organ dysfunctions.

Condition or disease Intervention/treatment Phase
Sepsis Drug: hydrocortisone Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis (Steroids in Paediatric Sepsis, StePS) - a Randomised Pilot Study
Study Start Date : April 2008
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Arm Intervention/treatment
Experimental: Treatment
Patients in this arm will be given the following IMP intraveneously at 6 hour intervals - hydrocortisone (100mg/m2/24 hours)
Drug: hydrocortisone
Patients will be assigned to treatment with hydrocortisone at 100mg/m2/24 hours in 4 divided doses (25 mg/m2/q 6 hourly) for 8 doses (48 hours) in phase 1 of study (45 patients, 30 receive IMP) or 20 doses (120 hours) in phase 2 (45 patients, 30 receive IMP).
Other Names:
  • Solu-Cortef®
  • Hydrocortisone sodium succinate

No Intervention: Control
in each phase of study 15 patients will receive no IMP as control arm

Primary Outcome Measures :
  1. primary efficacy endpoint is all cause mortality [ Time Frame: 28 days ]
  2. primary toxicity endpoint is Serious Adverse Events, excluding sepsis-related events specified as secondary outcomes [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. PIM2 [ Time Frame: entry ]
  2. PELOD [ Time Frame: daily to 28 days or PICU discharge ]
  3. ICU mortality [ Time Frame: 28 days ]
  4. time until shock reversal, defined as cessation of inotropic support for 24 hours [ Time Frame: 28 days ]
  5. time to resolution of multiorgan dysfunction [ Time Frame: 28 days ]
  6. time to resolution of base deficit [ Time Frame: 28 days ]
  7. time to resolution of lactate [ Time Frame: 28 days ]
  8. time to decision to discharge from ICU [ Time Frame: 28 days ]
  9. laboratory analysis of adrenal function [ Time Frame: 6 days and convalescence ]
  10. laboratory analysis of inflammatory parameters (defined in protocol) [ Time Frame: 6 days and convalescence ]
  11. laboratory analysis of coagulation parameters (defined in protocol) [ Time Frame: 6 days and convalescence ]

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Months to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Severe sepsis where enrolment can occur within 20 hours of first contact with paediatric intensive care, or within 20 hours of the diagnosis of severe sepsis when this diagnosis is made on PICU. Randomisation should occur within 24 hours of first contact with paediatric intensive care, or within 24 hours of the diagnosis of severe sepsis when this diagnosis is made on PICU.
  • Requiring mechanical ventilation (The subjects must be mechanically ventilated for entry into the study but this is not time limited. It is routine practice at study centres to pre-emptively ventilate children with evolving sepsis)

Exclusion Criteria:

  • Concomitant steroid therapy, vasopressor treatment >24 hrs or use of etomidate (not recommended for use in children less than 10 years and selectively inhibits 11 beta-hydroxylase)
  • Patients who have a recognised indication for steroids
  • Other immunosuppressive/immunomodulatory therapy (not including intravenous immunoglobulin which is considered standard therapy in toxic shock syndrome and may be given for this indication)
  • Significant immunocompromise (eg HIV infection)
  • Advanced malignancy
  • Burns
  • Cardiopulmonary resuscitation
  • Children not likely to survive the time period of the maximum study intervention (5 days)
  • Patients who have undergone organ transplantation (including bone marrow transplantation)
  • Patients undergoing plasma exchange or whole blood exchange transfusion
  • Treatment with an investigational drug or device within the last 30 days prior to enrolment.
  • Patients who have experienced a prior episode of infection or sepsis during the current hospitalisation.
  • Patients who are pregnant (a pregnancy test will be carried out for females of 11 years and above as is standard practice for clinical trials).
  • Immediate families of investigators or site personnel directly affiliated with the study. Immediate family is defined as child or sibling, whether biological or legally adopted.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00732277

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United Kingdom
Bristol Royal Hospital for Children
Bristol, UK, United Kingdom, BS2 8BJ
Imperial College Healthcare NHS Trust
London, UK, United Kingdom, W2 1NY
Southampton University Hospitals NHS Trust
Southampton, UK, United Kingdom, SO16 6YD
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust
Imperial College London
St Mary's NHS Trust
University of Bristol
University Hospitals Bristol NHS Foundation Trust
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Study Chair: Saul N Faust, MBBS PhD University of Southampton
Principal Investigator: Simon Nadel, MB BS Imperial College London
Study Director: Robert S Heyderman, MBBS PhD University of Liverpool
Study Director: Diana M Gibb, MBChB MD Medical Research Council
Study Director: Michael Levin, MBBCH PhD Imperial College London
Principal Investigator: Andrew Wolf, MBBChir MD Univeristy of Bristol
Study Director: John V Pappachan, MB BChir University Hospital Southampton NHS Foundation Trust
Study Director: Sarah Walker, MA PhD Medical Research Council
Study Director: Carrol Gamble, PhD University of Liverpool / MCRN Clinical Trials Unit

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Responsible Party: University Hospital Southampton NHS Foundation Trust Identifier: NCT00732277    
Other Study ID Numbers: RHM CHI 434
2007-002788-28 ( EudraCT Number )
07/H0504/139 ( Other Identifier: Southampton & South West Hampshire REC )
First Posted: August 11, 2008    Key Record Dates
Last Update Posted: May 6, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University Hospital Southampton NHS Foundation Trust:
Additional relevant MeSH terms:
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Systemic Inflammatory Response Syndrome
Pathologic Processes
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents