IgNiTE: Immunoglobulin in the treatment of encephalitis
Research type
Research Study
Full title
A phase III multi-centre randomised, double blind, placebo controlled trial to assess the role of intravenous immunoglobulin in the management of children with encephalitis (The IgNiTE study)
IRAS ID
156215
Contact name
Andrew Pollard
Contact email
Sponsor organisation
Oxford University Hospitals NHS Foundation Trust
Eudract number
2014-002997-35
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Research Summary
Encephalitis means inflammation of the brain and there are lots of different causes. Encephalitis could be caused by an infection (infectious encephalitis) or by the body’s immune system turning against itself by producing proteins that attack the brain called auto-antibodies (immune mediated encephalitis). For up to two-thirds of cases, the cause is unknown. Encephalitis is an important health problem. Despite the current standard of care, up to 20% of affected children die while up to 50% end up with significant problems. This highlights the need for newer treatment options. There is some evidence that pooled antibody from blood donors (intravenous immunoglobulin) also known as IVIG may improve outcomes for children with encephalitis. However, the evidence is only based on a small number of children or those with specific types of encephalitis. There are no research studies that have looked at the effect of IVIG when used to treat a large number of children, regardless of the type of encephalitis that they have. Also, although some doctors may use IVIG to treat children with encephalitis, this is often given late in the illness so we do not know the effect of IVIG when used early after diagnosis. In this study, we would like to find out whether early (within five days of hospitalisation) treatment with IVIG benefits children with encephalitis. We will be comparing the children who are treated with IVIG to those who are not. We will enrol 308 children between 6 weeks and 16 years. They will be randomly allocated to two groups to receive either IVIG or placebo (a ‘treatment’ that looks like IVIG but has no medical effect in encephalitis) in addition to standard treatment. Every child will have an equal chance of being allocated to each group. Children will be recruited from NHS hospitals in England, Wales, Scotland, and Northern Ireland. All children will be followed up for 12 months after treatment and we will be collecting information on their health and wellbeing through the use of questionnaires, brain scan and neuropsychologist (an expert who studies how the brain works). The study is funded by the National Institute for Health Research and is coordinated by the Department of Paediatrics, University of Oxford.
Summary of Results
The IgNiTE study aimed to investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness. Encephalitis is the major cause of illness and death globally, characterised by inflammation of the brain parenchyma causing neurological dysfunction which manifests acutely as altered mental state and can have long-term sequalae including neurological disability and seizures. This disease is more prevalent in children than adults, and especially in high-income countries, associated with high global economic, healthcare and social burden.
We assessed the role of intravenous immunoglobulin in the management of children with encephalitis. IgNiTE was a randomised, double blinded, parallel arm, placebo-controlled study to compare early IVIG treatment with placebo in the treatment of childhood encephalitis in individuals aged 6 months to 16 years.
The study was proposed to be conducted across 21 National Health Service (NHS) hospitals in the UK. Participants were to be followed up for 12 months after randomisation, with outcomes assessed during the acute admission, at 4–8 weeks after discharge from acute care, at 6 months after randomisation, and 12 months after randomisation. In actual, 18 volunteers (children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis) 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.
Two doses (1 g/kg/dose) of either IVIG or matching placebo was given 24–36 hours apart, in addition to standard treatment to volunteers.
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.
Our results showed a primary outcome was a ‘good recovery’ at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended. The secondary outcome measures on the other hand were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data.
Conclusively, 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.REC name
South Central - Oxford A Research Ethics Committee
REC reference
14/SC/1416
Date of REC Opinion
29 Dec 2014
REC opinion
Further Information Favourable Opinion