TY - JOUR
T1 - Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE)
T2 - a randomised controlled trial
AU - Hill, Matilda
AU - Iro, Mildred
AU - Sadarangani, Manish
AU - Absoud, Michael
AU - Cantrell, Liberty
AU - Chong, Kling
AU - Clark, Christopher
AU - Easton, Ava
AU - Gray, Victoria
AU - Kneen, Rachel
AU - Lim, Ming
AU - Liu, Xinxue
AU - Pike, Michael
AU - Solomon, Tom
AU - Vincent, Angela
AU - Willis, Louise
AU - Yu, Ly Mee
AU - Pollard, Andrew J.
N1 - Funding Information:
This project was funded by the National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation programme (grant number 12/212/15). The investigational medicinal product (IMP), intravenous immunoglobulin (Privigen) was provided by CSL Behring.
Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
PY - 2023/11/9
Y1 - 2023/11/9
N2 - 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.
AB - 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.
KW - clinical trials
KW - developmental neurology & neurodisability
KW - paediatric infectious disease & immunisation
KW - paediatric neurology
UR - http://www.scopus.com/inward/record.url?scp=85176455864&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2023-072134
DO - 10.1136/bmjopen-2023-072134
M3 - Article
C2 - 37945292
AN - SCOPUS:85176455864
SN - 2044-6055
VL - 13
JO - BMJ Open
JF - BMJ Open
IS - 11
M1 - e072134
ER -
