ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial
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 imm...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2016-11-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/6/11/e012356.full |
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| author | R Kneen M Lim A Vincent A J Pollard W K Chong L-M Yu M A Iro M Sadarangani M Absoud C A Clark A Easton V Gray M Pike T Solomon L Willis |
| author_facet | R Kneen M Lim A Vincent A J Pollard W K Chong L-M Yu M A Iro M Sadarangani M Absoud C A Clark A Easton V Gray M Pike T Solomon L Willis |
| author_sort | R Kneen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-64c6cb81a7fa4498b9a6c9fa0ea0fa38 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2016-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-64c6cb81a7fa4498b9a6c9fa0ea0fa382025-02-11T12:10:12ZengBMJ Publishing GroupBMJ Open2044-60552016-11-0161110.1136/bmjopen-2016-012356ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trialR Kneen0M Lim1A Vincent2A J Pollard3W K Chong4L-M Yu5M A Iro6M Sadarangani7M Absoud8C A Clark9A Easton10V Gray11M Pike12T Solomon13L Willis14Alder Hey Children’s NHS Foundation Trust, Liverpool, UK1School of Medicine14Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UKprofessor of paediatric infection and immunity, director of the Oxford Vaccine Group, honorary consultant paediatrician5Department of Radiology, Great Ormond Street Hospital for Children, London, UK15Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK1Oxford Vaccine Group, Department of Paediatrics, University of Oxford and NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK1Oxford Vaccine Group, Department of Paediatrics, University of Oxford and NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK4Department 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, UK6Institute of Child Health, University College London, London, UK7The Encephalitis Society, Malton, North Yorkshire, UK8Psychological services (Paediatrics), Alder Hey Children`s NHS Foundation Trust, Liverpool, UK11Department of Paediatric Neurology, Oxford University Hospitals NHS Trust, Oxford, UK9Institute of Infection and Global Health, University of Liverpool, Liverpool, UK1Oxford Vaccine Group, Department of Paediatrics, University of Oxford and NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UKIntroduction 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.https://bmjopen.bmj.com/content/6/11/e012356.full |
| spellingShingle | R Kneen M Lim A Vincent A J Pollard W K Chong L-M Yu M A Iro M Sadarangani M Absoud C A Clark A Easton V Gray M Pike T Solomon L Willis ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial BMJ Open |
| title | ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial |
| title_full | ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial |
| title_fullStr | ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial |
| title_full_unstemmed | ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial |
| title_short | ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial |
| title_sort | immunoglobulin in the treatment of encephalitis ignite protocol for a multicentre randomised controlled trial |
| url | https://bmjopen.bmj.com/content/6/11/e012356.full |
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