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

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.

• Authors: M A Iro, M Sadarangani, M Absoud, W K Chong, C A Clark, A Easton, V Gray, R Kneen, M Lim, M Pike, T Solomon, A Vincent, L Willis, L-M Yu, A J Pollard
• Journal: BMJ open (BMJ Open) Vol. 6 Issue 11 Pg. e012356 (11 03 2016) ISSN: 2044-6055 [Electronic] England
• PMID: 27810972 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Chemical References

• Immunoglobulins, Intravenous
• Immunologic Factors

Topics

• Adolescent
• Child
• Child, Preschool
• Clinical Protocols
• Encephalitis (drug therapy, immunology)
• Hashimoto Disease (drug therapy, immunology)
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Immunologic Factors (therapeutic use)
• Infant
• Infectious Encephalitis (drug therapy, immunology)
• Pediatrics
• Research Design