Clinical trial NCT02398994: A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis
Official title: A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin (IVIg) Versus Standard Therapy for the Treatment of Transverse Myelitis in Adults and Children
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myelitis, Transverse
Neuromyelitis Optica
Keywords: Clinical Trials Unit
Pediatric
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: King's College London
name: Barts and the London School of Medicine and Dentistry
name: Cardiff University
name: University College, London
name: King's College Hospital NHS Trust
name: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Barts & The London NHS Trust
name: Alder Hey Children's NHS Foundation Trust
name: Walton Centre NHS Foundation Trust
name: Oxford University Hospitals NHS Trust
name: Birmingham Women's and Children's NHS Foundation Trust
name: University Hospital Birmingham NHS Foundation Trust
name: Cardiff and Vale University Health Board
name: North Bristol NHS Trust
name: University Hospitals Bristol and Weston NHS Foundation Trust
name: Manchester University NHS Foundation Trust
name: Northern Care Alliance NHS Foundation Trust
name: University Hospital Southampton NHS Foundation Trust
name: Newcastle-upon-Tyne Hospitals NHS Trust
name: Nottingham University Hospitals NHS Trust
name: NHS Lothian
First posted: 2015-03-26
Enrollment: 2
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multi-center randomized controlled trial evaluates if the addition of intravenous immunoglobulin to standard treatment of corticosteroids improves outcome in children and adults with first episode of Transverse Myelitis of Neuro-myelitis optica. Half of participants will receive corticosteroids alone, whilst the other half will receive corticosteroids plus intravenous immunoglobulin.

Detailed description: Transverse myelitis (TM) is a severe demyelinating condition predominantly affecting young people, which causes significant long-term disability in approximately one third. Current initial treatment is with corticosteroids, although evidence for their use is based on extrapolation from trials in adult multiple sclerosis relapses. In view of the severity of the condition, additional treatments have been trialed.

Intravenous immunoglobulin (IVIG) is often used as second-line treatment in steroid-unresponsive central nervous system demyelination, although evidence for its efficacy is limited to small case series and case reports. Randomized controlled trials have demonstrated that IVIG reduces inflammation and enhances remyelination in a number of neurological conditions, although there have been no randomized controlled trials testing its use in adults and children with TM.

This study will evaluate if additional and early treatment with IVIG is of extra benefit in TM when compared to the current standard therapy of intravenous steroids alone.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of

EITHER acute first onset transverse myelitis (using the TM Consortium Working Group 2002 criteria) - patients must fulfill all of the following criteria:

* Sensory, motor, or autonomic dysfunction attributable to spinal cord disease
* Bilateral signs and/or symptoms (not necessarily symmetric)
* Sensory level (except in young children \<5 years where this is difficult to evaluate)
* Lack of MRI brain criteria consistent with multiple sclerosis
* Progression to nadir between 4 h and 21 days

OR first presentation of neuromyelitis optica (using standardised criteria) - patients must fulfil both absolute criteria:

* Optic neuritis
* Acute myelitis, plus two out of three supportive criteria (as Aquaporin 4 antibody (AQP4) is often not available acutely, only the first two supportive criteria would be applied),
* Brain MRI not meeting criteria for Multiple Sclerosis (MS) at disease onset
* Spinal cord MRI with contiguous T2-weighted signal abnormality extending over three or more vertebral segments, indicating a relatively large lesion in the spinal cord
* AQP4 seropositive status

  * ASIA Impairment Score of A-C
  * Randomisation to occur no later than day 5 of steroids, and, if definitely known, within 21 days from symptom onset.
  * Give assent (8-16 years)/consent to participate in the trial

Exclusion Criteria:

* Contraindication to IVIG as stated in the summary of product characteristics (SmPC), or receiving IVIG for other reasons
* Previously known systemic autoimmune disease (e.g. systemic lupus erythematosus) or any evidence of systemic inflammation during current presentation.
* Direct infectious aetiology (e.g. varicella zoster)
* Previous episode of central nervous system (CNS) inflammatory demyelination
* Acute disseminated encephalomyelitis (ADEM)
* Other causes of myelopathy not thought to be due to myelitis (e.g. nutritional, ischaemic, tumour etc.)
* Other disease which would interfere with assessment of outcome measures
* Known pregnancy
* Circumstances which would prevent follow-up for 12 month

Primary outcomes:
measure: 2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E)
timeFrame: 6 months
Secondary outcomes:
measure: Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112)
timeFrame: 6 months
measure: Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring
timeFrame: 6 months
measure: EQ-5D-Y (for patients aged 8-12 years at presentation)
timeFrame: 6 months
measure: EQ-5D-5L (for patients aged 13 years or over at presentation)
timeFrame: 6 months
measure: International Spinal Cord Injury (SCI) Quality of Life Basic Data Set (for patients aged 13 years or over at presentation)
timeFrame: 6 months
measure: Client Service Receipt Inventory (CSRI)
timeFrame: 6 months
Other outcomes:
measure: International SCI Bladder/Bowel Data Set (for patients aged 13 years or over at presentation)
timeFrame: 6 months
measure: Paediatric Quality of Life Inventory™ (PedsQL) Parent Report for Toddlers (for patients aged 2-4 years at presentation)
timeFrame: 6 months
measure: Paediatric Quality of Life Inventory™(PedsQL) Parent Report for Young Children (for patients aged 5-7 years at presentation)
timeFrame: 6 months
measure: International SCI Pain Basic Data Set (for patients ages 13 years or over at presentation)
timeFrame: 6 months
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Bristol
country: United Kingdom
facility: University Hospital Bristol NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: Walton Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Great Ormond Street Children's Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: University of London and Bart's Health NHS Trust
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Newcastle-upon-Tyne Hospitals NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Southampton NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Ming Lim, MB, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Absoud M, Brex P, Ciccarelli O, Diribe O, Giovannoni G, Hellier J, Howe R, Holland R, Kelly J, McCrone P, Murphy C, Palace J, Pickles A, Pike M, Robertson N, Jacob A, Lim M. A multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin compared with standard therapy for the treatment of transverse myelitis in adults and children (STRIVE). Health Technol Assess. 2017 May;21(31):1-50. doi: 10.3310/hta21310.
citation: Absoud M, Gadian J, Hellier J, Brex PA, Ciccarelli O, Giovannoni G, Kelly J, McCrone P, Murphy C, Palace J, Pickles A, Pike M, Robertson N, Jacob A, Lim M. Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE). BMJ Open. 2015 May 25;5(5):e008312. doi: 10.1136/bmjopen-2015-008312.