Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis - a Randomised Pilot Study (StePS)
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|ClinicalTrials.gov Identifier: NCT00732277|
Recruitment Status : Completed
First Posted : August 11, 2008
Last Update Posted : May 6, 2016
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 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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
Patients in this arm will be given the following IMP intraveneously at 6 hour intervals - hydrocortisone (100mg/m2/24 hours)
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).
No Intervention: Control
in each phase of study 15 patients will receive no IMP as control arm
- primary efficacy endpoint is all cause mortality [ Time Frame: 28 days ]
- primary toxicity endpoint is Serious Adverse Events, excluding sepsis-related events specified as secondary outcomes [ Time Frame: 28 days ]
- PIM2 [ Time Frame: entry ]
- PELOD [ Time Frame: daily to 28 days or PICU discharge ]
- ICU mortality [ Time Frame: 28 days ]
- time until shock reversal, defined as cessation of inotropic support for 24 hours [ Time Frame: 28 days ]
- time to resolution of multiorgan dysfunction [ Time Frame: 28 days ]
- time to resolution of base deficit [ Time Frame: 28 days ]
- time to resolution of lactate [ Time Frame: 28 days ]
- time to decision to discharge from ICU [ Time Frame: 28 days ]
- laboratory analysis of adrenal function [ Time Frame: 6 days and convalescence ]
- laboratory analysis of inflammatory parameters (defined in protocol) [ Time Frame: 6 days and convalescence ]
- laboratory analysis of coagulation parameters (defined in protocol) [ Time Frame: 6 days and convalescence ]
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 ClinicalTrials.gov identifier (NCT number): NCT00732277
|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|
|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|