Children with severe sepsis requiring mechanical ventilation presenting within 12 hours of onset. The majority of children will either have community acquired sepsis (most commonly meningococcal or pneumococcal disease) or post operative infection. Few patients will have additional co-morbidities. MedDRA version: 9.1 Level: LLT Classification code 10040047 Term: Sepsis MedDRA version: 9.1 Level: LL
Conditions
Interventions
Trade Name: Solu-Cortef®
Product Name: Solu-Cortef® 100 mg or Hydrocortisone sodium succinate for injection BP 100 mg
Pharmaceutical Form: Powder for injection*
Sponsors
Southampton University Hospital NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Children 3 months to 14 years inclusive (to include children in puberty) •Severe sepsis within 12 hours of onset •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) 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 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. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 intervention •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 •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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy endpoint is all cause mortality at 28 days, and the primary toxicity endpoint is Serious Adverse Events, excluding sepsis-related events specified as secondary outcomes below (see section 3.10.3.1).; Secondary Objective: One of the aims of this pilot study is to identify outcome measures (clinical and laboratory) suitable for a large RCT that •vary over time in one or other of the arms •provide a sensitive measure of any differences •are clinically important and are practical to collect on all subjects (to avoid bias). Following completion of enrolment, we will analyse (i) changes over time (ii) differences between arms for each potential outcome measure and their relevance to sepsis (iii) completeness of data. The choice of final outcome measures for a large simple RCT will be a compromise between these aspects. ;Primary end point(s): The primary efficacy endpoint is all cause mortality at 28 days, and the primary toxicity endpoint is Serious Adverse Events, excluding sepsis-related events specified as secondary outcomes. | — |
Countries
United Kingdom
Outcome results
None listed