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

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.

Conditions

• Sepsis

Interventions

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).

Sponsors & Collaborators

• Imperial College London

  collaborator OTHER

• St Mary's NHS Trust

  collaborator OTHER_GOV

• University of Bristol

  collaborator OTHER

• University Hospitals Bristol and Weston NHS Foundation Trust

  collaborator OTHER

• University Hospital Southampton NHS Foundation Trust

  lead OTHER

Principal Investigators

• Saul N Faust, MBBS PhD · University of Southampton

• Simon Nadel, MB BS · Imperial College London

• Robert S Heyderman, MBBS PhD · University of Liverpool

• Diana M Gibb, MBChB MD · Medical Research Council

• Michael Levin, MBBCH PhD · Imperial College London

• Andrew Wolf, MBBChir MD · Univeristy of Bristol

• John V Pappachan, MB BChir · University Hospital Southampton NHS Foundation Trust

• Sarah Walker, MA PhD · Medical Research Council

• Carrol Gamble, PhD · University of Liverpool / MCRN Clinical Trials Unit

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

3 Months

Max Age

14 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-04-30

Primary Completion

2012-04-30

Completion

2012-04-30

Countries

• United Kingdom

Study Locations