title: Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE).
abstract: BACKGROUND
  Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord which causes motor and sensory disturbance and limited recovery in 50% of patients. Standard treatment is steroids, and patients with more severe disease appear to respond to plasma exchange (PLEX). Intravenous immunoglobulin (IVIG) has also been used as an adjunct to steroids, but evidence is lacking. We propose the first randomised control trial in adults and children, to determine the benefit of additional treatment with IVIG.
  
  
  METHODS
  170 adults and children aged over 1 year with acute first episode TM or neuromyelitis optica (with myelitis) will be recruited over a 2.5-year period and followed up for 12 months. Participants randomised to the control arm will receive standard therapy of intravenous methylprednisolone (IVMP). The intervention arm will receive the above standard therapy, plus additional IVIG. Primary outcome will be a 2-point improvement on the American Spinal Injury Association (ASIA) Impairment scale at 6 months postrandomisation by blinded assessors. Additional secondary and tertiary outcome measures will be collected: ASIA motor and sensory scales, Kurtzke expanded disability status scale, International Spinal Cord Injury (SCI) Bladder/Bowel Data Set, Client Services Receipt Index, Pediatric Quality of Life Inventory, EQ-5D, SCI Pain and SCI Quality of Life Data Sets. Biological samples will be biobanked for future studies. After 6-months' follow-up of the first 52 recruited patients futility analysis will be carried out. Health economics analysis will be performed to calculate cost-effectiveness. After 6 months' recruitment futility analysis will be performed.
  
  
  BACKGROUND
  Research Ethics Committee Approval was obtained: 14/SC/1329. Current protocol: v3.0 (15/01/2015). Study findings will be published in peer-reviewed journals.
  
  
  BACKGROUND
  This study is registered with EudraCT (REF: 2014-002335-34), Clinicaltrials.gov (REF: NCT02398994) and ISRCTN (REF: 12127581).
authors.affiliation: Department of Children's Neurosciences, Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Absoud
authors.affiliation: Department of Children's Neurosciences, Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Gadian
authors.affiliation: Department of Biostatistics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Hellier
authors.affiliation: Department of Neurology, King's College Hospital NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Brex
authors.affiliation: UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: O
authors.initials: O
authors.lastname: Ciccarelli
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, University of London and Bart's Health NHS Trust, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: King's Clinical Trials Unit, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Kelly
authors.affiliation: Centre for the Economics of Mental and Physical Health, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: McCrone
authors.affiliation: King's Clinical Trials Unit, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Murphy
authors.affiliation: Department of Neurology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: J
authors.initials: J
authors.lastname: Palace
authors.affiliation: Department of Biostatistics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pickles
authors.affiliation: Department of Paediatric Neurology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Pike
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University and Cardiff and Vale NHS Trust, Cardiff, UK.
authors.forename: N
authors.initials: N
authors.lastname: Robertson
authors.affiliation: The Walton Centre, Walton Centre NHS Foundation Trust, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Department of Children's Neurosciences, Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Lim
mesh_terms: D000328:Adult; D002648:Child; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000627:therapeutic use; D009188:Myelitis, Transverse / Q000188:drug therapy*; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries; D059039:Standard of Care; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous; D008775:Methylprednisolone
keywords: HEALTH ECONOMICS; IMMUNOLOGY; NEUROLOGY; STATISTICS & RESEARCH METHODS