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

OVG 2014/05

This is a phase III multi-centre randomised, double blind, placebo controlled trial to assess the role of intravenous immunoglobulin in the treatment of children with encephalitis. The primary objective is to find out whether early use of IVIG treatment improves neurological outcomes of children with encephalitis. 308 children with encephalitis, aged 6 weeks to 16 years will be recruited in 30 hospitals in the United Kingdom. Participants will be randomised to receive two doses of IVIG or matching placebo in addition to other standard treatments, within the first five days of hospital admission. Each participant will be followed up for 12 months. During this period, information on clinical, radiological and laboratory investigations will be collected. Neurological outcomes will be assessed by the use of questionnaires at 6 and 12 months, and a neuropsychological assessment at 12 months.

2016-01-01

2022-09-01

2022-09-01

Completed

Early phase I

18

Inclusion Criteria: 1. 6 weeks to 16 years of age (day before 17th birthday) AND 2. Acute (within 24 hours) or sub-acute (between 24 hours and 4 weeks) onset of altered mental state (reduced or altered conscious level, irritability, altered personality or behaviour, lethargy) not attributable to a metabolic cause AND 3. At least two of: 1. fever \> 38 degrees Celsius within 72 hours before or after presentation to hospital 2. brain imaging evidence consistent with encephalitis or immune-mediated encephalopathy that is either new from prior studies or appears acute in onset 3. CSF pleocytosis \> 4 white blood cells per microlitre 4. generalised or partial seizures not fully attributable to a pre-existing seizure disorder 5. new onset focal neurological signs (including movement disorders) for \> 6 hours 6. abnormality on EEG that is consistent with encephalitis and not clearly attributable to another cause AND 4. Parent/guardian/legal representative able to give informed consent Exclusion Criteria: * high clinical suspicion of bacterial meningitis or TB meningitis (for example: presence of frankly purulent CSF; CSF WBCs \>1000/microlitre; bacteria on Gram stain and/or culture) * Traumatic brain injury * Known metabolic encephalopathy * toxic encephalopathy (i.e. encephalopathy secondary to exposure to intoxicants, including alcohol, prescription or recreational drugs) * hypertensive encephalopathy/posterior reversible encephalopathy syndrome * pre-existing demyelinating disorder; pre-existing antibody mediated CNS disorder; pre-existing CSF diversion * ischaemic or haemorrhagic stroke * children with a contra-indication to IVIG or albumin (i.e. history of anaphylactic reaction to IVIG or albumin, known IgA deficiency and history of hypersensitisation) * Known hypercoagulable state * significant renal impairment defined as GFR of 29mls/min/1.73m2 and below (Chronic Kidney Disease Stage 4) * Known hyperprolinaemia * Known to be pregnant * Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial * participants who are being actively followed up in another research trial involving an investigational medicinal product * Administration of study drug not feasible within 120 hours from hospital admission as determined by the study team * Any other condition which, in the opinion of the investigator, may interfere with the ability to fulfil study requirements, especially relating to the primary objective of the study (this includes plans to be outside the UK for more than 12 months after enrolment)

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2024-03-04