Table 1

Secondary and tertiary outcomes

Data collection time pointOutcome measure
Secondary outcomes
Clinical and neurological
 During hospital inpatient stay

  • Glasgow coma score

  • Neurological examination findings as documented by the clinical team

  • Duration of invasive ventilation (if ventilated)

  • Length of intensive care unit (ICU) stay in a subset of children admitted to ICU

  • Length of hospitalisation

 Around 4–6 weeks after discharge from acute care

  • Strength and Difficulties Questionnaire (SDQ)

  • Adaptive Behavior Assessment System-Second Edition (ABAS-II)

  • Peds Quality of Life scoring algorithm

  • Liverpool Outcome Score

  • Gross Motor Function Classification System (GMFCS)

 Around 6 months (±4 weeks) after randomisation

  • GOSE-Peds

 Around 12 months (±4 weeks) after randomisation

  • New diagnosis of epilepsy

  • Use of antiepileptic treatment

  • Strength and Difficulties Questionnaire (SDQ)

  • Adaptive Behavior Assessment System-Second Edition (ABAS-II)

  • Peds Quality of Life (PedsQoL) scoring algorithm

  • Liverpool Outcome Score (LOS)

  • Gross Motor Function Classification System (GMFCS)

  • Blinded neuropsychologist assessment of cognitive functioning using age appropriate developmental scales (Bayley Scales for Infant Development (BSID-III)/Wechsler preschool and Primary Scale of Intelligence III (WPPSI-III)/Wechsler Intelligence Scale for Children IV (WISC-IV)

 12 months after randomisationProportion of deaths occurring in participants
Radiological
 Around 6 months after randomisationBrain MRI to assess lesion resolution, presence of new lesions and distribution of persisting disease
Safety
 24–48 hours after the second IMP doseFull blood count check to monitor for haemolysis
 First 5 days after each dose of trial treatmentAdverse events of special interest (AESIs)
 Up to 6 months after randomisationSerious adverse events (SAEs)
 Up to 12 months after randomisationSerious adverse reactions (SARs)Suspected Unexpected Serious Adverse Reactions (SUSARs)
AutoimmunePresence of and comparison of levels of specific neuronal antibodies in serum and/or CSF samples (where lumbar puncture is performed as part of routine care) before and after administration of trial treatment
Tertiary outcomes

  1. Correlate MRI findings with neurological outcomes

  2. Correlate clinical and laboratory parameters with neurological outcomes

  3. Comparison of brain MRI findings with aetiological diagnosis

  4. Identification of specific DNA sequence and structural genetic variants in patients with encephalitis

  5. The following will be assessed before and after receipt of trial treatment:

    • Comparison of inflammatory cytokines

    • Assessment of regulatory T-cell frequency and function in blood and/or CSF

    • Measurement of inflammatory markers in blood and/or CSF

    • Analysis of gene expression in whole blood

    • Comparison of the host inflammatory pathways and correlation with clinical parameters