{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:58:41Z","timestamp":1779926321728,"version":"3.53.1"},"reference-count":30,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100001922","name":"Efficacy and Mechanism Evaluation Programme","doi-asserted-by":"publisher","award":["12\/212\/15"],"award-info":[{"award-number":["12\/212\/15"]}],"id":[{"id":"10.13039\/501100001922","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2016,8,19]]},"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>308 children (6\u2005months to 16\u2005years) with a diagnosis of acute\/subacute encephalitis will be recruited in \u223c30 UK hospitals and randomised to receive 2 doses (1\u2005g\/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 \u2018good recovery\u2019 (score of 2 or lower on the Glasgow Outcome Score Extended\u2014paediatric version), at 12\u2005months after randomisation. Additional secondary neurological measures will be collected at 4\u20136\u2005weeks after discharge from acute care and at 6 and 12\u2005months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>This trial has been approved by the UK National Research Ethics committee (South Central\u2014Oxford 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration numbers<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02308982?term=nct02308982&amp;rank=1\" ext-link-type=\"uri\">NCT02308982<\/jats:ext-link>, EudraCT201400299735 and<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"isrctn\" xlink:href=\"15791925\">ISRCTN15791925<\/jats:ext-link>; Pre-results.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2016-012356","type":"journal-article","created":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T02:00:15Z","timestamp":1478224815000},"page":"e012356","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["<i>I<\/i>mmuno<i>g<\/i>lobuli<i>N<\/i><i>i<\/i>n the<i>T<\/i>reatment of<i>E<\/i>ncephalitis (IgNiTE): protocol for a multicentre randomised controlled trial"],"prefix":"10.1136","volume":"6","clinical-trial-number":[{"clinical-trial-number":"isrctn15791925","registry":"10.18810\/isrctn"}],"author":[{"given":"M A","family":"Iro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sadarangani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Absoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W K","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C A","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Easton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Kneen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Willis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0331-7364","authenticated-orcid":false,"given":"L-M","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Pollard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,11,3]]},"reference":[{"key":"2024051610274217000_6.11.e012356.1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit458"},{"key":"2024051610274217000_6.11.e012356.2","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.3201\/eid1909.130064","article-title":"New estimates of incidence of encephalitis in England","volume":"19","author":"Granerod","year":"2013","journal-title":"Emerging Infect Dis"},{"key":"2024051610274217000_6.11.e012356.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2011.11.013"},{"key":"2024051610274217000_6.11.e012356.4","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-2702"},{"key":"2024051610274217000_6.11.e012356.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00401-9"},{"key":"2024051610274217000_6.11.e012356.6","doi-asserted-by":"publisher","DOI":"10.3201\/eid0902.020218"},{"key":"2024051610274217000_6.11.e012356.7","doi-asserted-by":"publisher","DOI":"10.1086\/341405"},{"key":"2024051610274217000_6.11.e012356.8","doi-asserted-by":"crossref","unstructured":"Easton A . 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