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

This study has been completed.
Sponsor:
Collaborators:
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.
ClinicalTrials.gov Identifier:
NCT00732277
First received: August 7, 2008
Last updated: May 5, 2016
Last verified: May 2016
  Purpose

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 Intervention Phase
Sepsis
Drug: hydrocortisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis (Steroids in Paediatric Sepsis, StePS) - a Randomised Pilot Study

Resource links provided by NLM:


Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:
  • primary efficacy endpoint is all cause mortality [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • primary toxicity endpoint is Serious Adverse Events, excluding sepsis-related events specified as secondary outcomes [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PIM2 [ Time Frame: entry ] [ Designated as safety issue: No ]
  • PELOD [ Time Frame: daily to 28 days or PICU discharge ] [ Designated as safety issue: No ]
  • ICU mortality [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • time until shock reversal, defined as cessation of inotropic support for 24 hours [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • time to resolution of multiorgan dysfunction [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • time to resolution of base deficit [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • time to resolution of lactate [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • time to decision to discharge from ICU [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • laboratory analysis of adrenal function [ Time Frame: 6 days and convalescence ] [ Designated as safety issue: No ]
  • laboratory analysis of inflammatory parameters (defined in protocol) [ Time Frame: 6 days and convalescence ] [ Designated as safety issue: No ]
  • laboratory analysis of coagulation parameters (defined in protocol) [ Time Frame: 6 days and convalescence ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: April 2008
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Months to 14 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732277

Locations
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
Investigators
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
  More Information

Additional Information:
Publications:

Responsible Party: University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier: NCT00732277     History of Changes
Other Study ID Numbers: RHM CHI 434  2007-002788-28  07/H0504/139 
Study First Received: August 7, 2008
Last Updated: May 5, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University Hospital Southampton NHS Foundation Trust.:
sepsis
septicaemia
septicemia
paediatric
pediatric
children

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on August 24, 2016