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BMJ Open. 2016 Nov 3;6(11):e012356. doi: 10.1136/bmjopen-2016-012356.

ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial.

Author information

1
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
2
Department of Paediatrics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
3
Vaccine Evaluation Center, BC Children's Hospital Research Institute, University of British Columbia, Vancouver BC, Canada.
4
Department of Children's Neurosciences, Evelina London Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK.
5
Department of Radiology, Great Ormond Street Hospital for Children, London, UK.
6
Institute of Child Health, University College London, London, UK.
7
The Encephalitis Society, Malton, North Yorkshire, UK.
8
Psychological services (Paediatrics), Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
9
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
10
Littlewoods Neuroscience Foundation, Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
11
Department of Paediatric Neurology, Oxford University Hospitals NHS Trust, Oxford, UK.
12
National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.
13
Walton Centre NHS Foundation Trust, Liverpool, UK.
14
Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
15
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Abstract

INTRODUCTION:

Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis.

METHODS AND ANALYSIS:

308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is 'good recovery' (score of 2 or lower on the Glasgow Outcome Score Extended-paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4-6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed.

ETHICS AND DISSEMINATION:

This trial has been approved by the UK National Research Ethics committee (South Central-Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals.

TRIAL REGISTRATION NUMBERS:

NCT02308982, EudraCT201400299735 and ISRCTN15791925; Pre-results.

KEYWORDS:

ADEM; GOSE-Peds; autoimmune; encephalitides; immune-mediated

PMID:
27810972
PMCID:
PMC5129051
DOI:
10.1136/bmjopen-2016-012356
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

CSL Behring have provided the study IMP (IVIG) and funded manufacture of placebo and the supply and distribution of IMP and placebo. AJP reports grants from NIHR EME programme, during the conduct of the study. The University of Oxford and AV hold patents for VGKC-complex antibody tests, licensed to Euroimmun AG, and receive royalties. The neuroimmunology work in the described trial is funded through the MRC/NIHR grant. MA serves on the data safety monitoring board for a study sponsored by Neurim Pharmaceuticals and is on the editorial advisory board for the International Journal of Language and Communication Disorders. MAI and LW report salary from the NIHR EME grant. ML has received consultation fees from CSL Behring, travel grants from Merck Serono and been awarded educational grants to organise meetings by Novartis, Biogen Idec, Merck Serono and Bayer. MS reports grants from Pfizer, outside the submitted work. TS is supported by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at Liverpool. AE, LW, L-MY, MP, MS, RK and WKC have nothing to disclose.

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