Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsors and Collaborators: |
Southampton University Hospitals NHS Trust Imperial College London St Mary's NHS Trust University of Bristol United Bristol Healthcare NHS Trust |
---|---|
Information provided by: | Southampton University Hospitals NHS Trust |
ClinicalTrials.gov Identifier: | NCT00732277 |
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 |
---|---|---|
Paediatric Sepsis Pediatric Sepsis |
Drug: hydrocortisone |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment |
Official Title: | Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis (Steroids in Paediatric Sepsis, StePS) - a Randomised Pilot Study |
Estimated Enrollment: | 90 |
Study Start Date: | April 2008 |
Estimated Study Completion Date: | January 2010 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Treatment: Experimental |
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).
|
Control: No Intervention
in each phase of study 15 patients will receive no IMP as control arm
|
This is an open randomised prospective pilot exploratory study of corticosteroid replacement therapy in three centres. Adrenal function measurements will be assessed on entry to the study. To investigate the inflammatory profile and the impact of corticosteroid replacement, blood will be taken for cytokine and coagulation protein analysis. This study will provide the pilot data necessary for the design of a definitive trial of corticosteroid replacement therapy with the identification of variables likely to improve our ability to stratify patients for intervention and the mechanistic characterisation of the modulatory effects of steroids on inflammation in children with severe sepsis. Enrolment will be undertaken in two stages (see flowsheet diagrams in protocol). Forty five eligible children will be randomly allocated to steroid replacement therapy for 2 days (n=30) or intensive investigation without intervention (n=15) in a 2:1 randomisation (stage 1); 45 subjects (stage 2) will then be randomly allocated to steroid replacement therapy for 5 days (n=30) or intensive investigation without intervention (n=15). Randomisation will the undertaken in accordance with a computer−generated list and will be stratified by age (<1 years; 1 year or more). Progression from stage 1 to stage 2 will follow an interim analysis by a Trial Monitoring Group to ensure safety. This escalating approach will provide safety data, information on length of therapy and an assessment of possible clinical and laboratory endpoints in addition to mortality, reducing the potential for adverse events in the pilot phase while providing data relevant to this population. A large excess of serious adverse events in stage 1 will result in study termination. After careful consideration by the investigators and during the peer review process, placebo will not be used in this study, which will inform a future large phase 3 randomised controlled trial.
RESEARCH PARTICIPANTS WILL RECEIVE THE FOLLOWING INTERVENTIONS THAT ARE NOT PART OF ROUTINE CLINICAL CARE (Please also refer to figures 1−4 in the protocol that we are unable to reproduce here): Children will be screened on admission to PICU. Entry into the study following consent involves a clinical test of endocrine function involving 2 blood tests. The list of procedures conducted in the study is as follows:
Ages Eligible for Study: | 3 Months to 14 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Saul N Faust, MBBS PhD | 44 23 8079 4989 | s.faust@soton.ac.uk |
Contact: Simon Nadel, MBBS | 44 20 7886 2494 | s.nadel@imperial.ac.uk |
United Kingdom, UK | |
Southampton University Hospitals NHS Trust | Recruiting |
Southampton, UK, United Kingdom, SO16 6YD | |
Contact: Saul N Faust, MBBS PhD 44 23 8079 4989 s.faust@soton.ac.uk | |
Contact: Helen Cracknell 44 7917 560685 helen.cracknell@suht.swest.nhs.uk | |
Principal Investigator: Saul N Faust | |
Sub-Investigator: John V Pappachan | |
Sub-Investigator: Michael Marsh | |
Sub-Investigator: Iain Macintosh | |
Sub-Investigator: Peter Wilson | |
Sub-Investigator: Kim Sykes | |
Sub-Investigator: Gareth Jones | |
Sub-Investigator: Serena Cotterell | |
Imperial College Healthcare NHS Trust | Not yet recruiting |
London, UK, United Kingdom, W2 1NY | |
Contact: Simon Nadel 44 20 7886 2494 s.nadel@imperial.ac.uk | |
Contact: Annabelle Smale Annabelle.Smale@imperial.nhs.uk | |
Principal Investigator: Simon Nadel | |
Sub-Investigator: Michael Levin | |
Sub-Investigator: Parviz Habibi | |
Sub-Investigator: David Inwald | |
Sub-Investigator: Mehrengise Cooper | |
Bristol Royal Hospital for Children | Not yet recruiting |
Bristol, UK, United Kingdom, BS2 8BJ | |
Contact: Andrew Wolf 44 7919 974721 awolfbch@aol.com | |
Contact: Natalie Fineman 44 117 342 0211 mdxnf@bristol.ac.uk | |
Principal Investigator: Andrew Wolf | |
Sub-Investigator: James Fraser | |
Sub-Investigator: Stephen Marriage | |
Sub-Investigator: Peter Davis | |
Sub-Investigator: Margrid Schindler | |
Sub-Investigator: David Grant | |
Sub-Investigator: Ian Jenkins | |
Sub-Investigator: Patricia Weir | |
Sub-Investigator: Peter Murphy |
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 | Southampton University Hospitals NHS Trust |
Study Director: | Sarah Walker, MA PhD | Medical Research Council |
Study Director: | Carrol Gamble, PhD | University of Liverpool / MCRN Clinical Trials Unit |
Responsible Party: | Southampton University Hospitals NHS Trust ( Director Of Research and Development ) |
Study ID Numbers: | RHM CHI 434, EudraCT: 2007-002788-28, NHS REC: 07/H0504/139 |
Study First Received: | August 7, 2008 |
Last Updated: | September 5, 2008 |
ClinicalTrials.gov Identifier: | NCT00732277 History of Changes |
Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
sepsis septicaemia septicemia |
paediatric pediatric children |
Anti-Inflammatory Agents Systemic Inflammatory Response Syndrome Sepsis Hydrocortisone |
Cortisol succinate Hydrocortisone acetate Inflammation |
Anti-Inflammatory Agents Systemic Inflammatory Response Syndrome Sepsis Hydrocortisone Pathologic Processes Cortisol succinate |
Therapeutic Uses Hydrocortisone acetate Infection Pharmacologic Actions Inflammation |