BMJ Open (Nov 2023)
Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial
- ,
- Simon Nadel,
- Claire Cameron,
- David Pace,
- Rachel Kneen,
- Matilda Hill,
- Federico Martinón-Torres,
- Tom Solomon,
- Mandy Wan,
- Angela Vincent,
- Michael Absoud,
- Patrick Waters,
- Manish Sadarangani,
- Xinxue Liu,
- Andrew J Pollard,
- Sanjay Bhate,
- Ly-Mee Yu,
- John Alexander,
- Sarosh Irani,
- David Kerr,
- Andrew Collinson,
- Ava Easton,
- William Whitehouse,
- Ming Lim,
- Emma Plested,
- Paul Heath,
- Dominic Smith,
- Michael Pike,
- Adilia Warris,
- Anna Riddell,
- Paddy McMaster,
- Simon Kerridge,
- Louise Willis,
- Christopher Clark,
- Victoria Gray,
- Jay Shetty,
- John Livingston,
- Kling Chong,
- Vishal Mehta,
- Charles Warlow,
- Jo Haviland,
- Alice Jollands,
- Shakeel Herwitker,
- Daniel O’Connor,
- Yama Mujadidi,
- Lauren Burke,
- Mildred Iro,
- Sagida Bibi,
- Liberty Cantrell,
- Mike Pike,
- Chris A. Clark,
- Sophie Bradshaw,
- Svetlana Milca,
- Mike Bale,
- Sonia Bale,
- Alan Percival,
- Meryn Voysey,
- Amy Beveridge,
- Amber Thompson,
- Parvinder Alley,
- Archana Desurkar,
- Elma Stephen,
- Steve Welch,
- Kayal Vijayakumar,
- Leena Mewasingh,
- Christian de Goede
Affiliations
- Simon Nadel
- Claire Cameron
- David Pace
- Rachel Kneen
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- Matilda Hill
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Federico Martinón-Torres
- Tom Solomon
- The Pandemic Institute, Liverpool, UK
- Mandy Wan
- Angela Vincent
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
- Michael Absoud
- Children`s Neurosciences, Evelina London Children`s Hospital Neurosciences Department, London, UK
- Patrick Waters
- Manish Sadarangani
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
- Xinxue Liu
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Andrew J Pollard
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Sanjay Bhate
- Ly-Mee Yu
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- John Alexander
- Sarosh Irani
- David Kerr
- Andrew Collinson
- Ava Easton
- The Encephalitis Society, Malton, North Yorkshire, UK
- William Whitehouse
- Ming Lim
- Children`s Neurosciences, Evelina London Children`s Hospital Neurosciences Department, London, UK
- Emma Plested
- Paul Heath
- Dominic Smith
- Michael Pike
- Department of Paediatric Neurology, Oxford University Hospitals NHS Trust, Oxford, UK
- Adilia Warris
- Anna Riddell
- Paddy McMaster
- Simon Kerridge
- Louise Willis
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Christopher Clark
- UCL Great Ormond Street Institute of Child Health, London, UK
- Victoria Gray
- Clinical Health Psychology, Alder Hey Children`s NHS Foundation Trust, Liverpool, UK
- Jay Shetty
- John Livingston
- Kling Chong
- UCL Great Ormond Street Institute of Child Health, London, UK
- Vishal Mehta
- Charles Warlow
- Jo Haviland
- Alice Jollands
- Shakeel Herwitker
- Daniel O’Connor
- Yama Mujadidi
- Lauren Burke
- Mildred Iro
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Sagida Bibi
- Liberty Cantrell
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Mike Pike
- Chris A. Clark
- Sophie Bradshaw
- Svetlana Milca
- Mike Bale
- Sonia Bale
- Alan Percival
- Meryn Voysey
- Amy Beveridge
- Amber Thompson
- Parvinder Alley
- Archana Desurkar
- Elma Stephen
- Steve Welch
- Kayal Vijayakumar
- Leena Mewasingh
- Christian de Goede
- DOI
- https://doi.org/10.1136/bmjopen-2023-072134
- Journal volume & issue
-
Vol. 13,
no. 11
Abstract
Objective To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness.Design Phase 3b multicentre, double-blind, randomised placebo-controlled trial.Setting Twenty-one hospitals in the UK.Participants Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308.Intervention Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24–36 hours apart, in addition to standard treatment.Main outcome measure The primary outcome was a ‘good recovery’ at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended.Secondary outcome measures The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data.Results 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG.Conclusions The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis.Trial registration number Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925.
