A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis

NCT02398994 | Terminated Phase 3 DMC

• 4 other identifiers: RJ115/N0652014-002335-3411/129/14812127581
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 18

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.

Conditions

Myelitis, Transverse; Neuromyelitis Optica

Keywords

Clinical Trials Unit; Pediatric

Outcome Measures

Primary Outcomes (1)

• 2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E)

  6 months

Secondary Outcomes (6)

• Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112)

  6 months

• Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring

  6 months

• EQ-5D-Y (for patients aged 8-12 years at presentation)

  6 months

• EQ-5D-5L (for patients aged 13 years or over at presentation)

  6 months

• International Spinal Cord Injury (SCI) Quality of Life Basic Data Set (for patients aged 13 years or over at presentation)

  6 months

Other Outcomes (4)

• International SCI Bladder/Bowel Data Set (for patients aged 13 years or over at presentation)

  6 months

• Paediatric Quality of Life Inventory™ (PedsQL) Parent Report for Toddlers (for patients aged 2-4 years at presentation)

  6 months

• Paediatric Quality of Life Inventory™(PedsQL) Parent Report for Young Children (for patients aged 5-7 years at presentation)

  6 months

Study Arms (2)

Intravenous Methylprednisolone

ACTIVE COMPARATOR

Paediatric patients - 30mg/kg or 500mg/m2 up to a maximum daily dose of 1g/day for 5 days. Adult patients - 1g/day for 5 days.

Drug: Intravenous Methylprednisolone

Intravenous Immunoglobulin

EXPERIMENTAL

Paediatric patients \<41.2kg - total dose of 2g/kg in divided doses over 2 days. All other patients - total dose of 2g/kg in divided doses over 5 days. PLUS Intravenous Methylprednisolone Pediatric patients - 30mg/kg or 500mg/m2 up to a maximum daily dose of 1g/day for 5 days. Adult patients - 1g/day for 5 days.

Drug: Intravenous Methylprednisolone; Drug: Intravenous Immunoglobulin

Interventions

Intravenous Methylprednisolone DRUG

Intravenous Immunoglobulin; Intravenous Methylprednisolone

Intravenous Immunoglobulin DRUG

Intravenous Immunoglobulin

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• King's College London: collaborator
• Barts and the London School of Medicine and Dentistry: collaborator
• Cardiff University: collaborator
• University College, London: collaborator
• King's College Hospital NHS Trust: collaborator
• Great Ormond Street Hospital for Children NHS Foundation Trust: collaborator
• Barts & The London NHS Trust: collaborator
• Alder Hey Children's NHS Foundation Trust: collaborator
• Walton Centre NHS Foundation Trust: collaborator
• Oxford University Hospitals NHS Trust: collaborator
• Birmingham Women's and Children's NHS Foundation Trust: collaborator
• University Hospital Birmingham NHS Foundation Trust: collaborator
• Cardiff and Vale University Health Board: collaborator
• North Bristol NHS Trust: collaborator
• University Hospitals Bristol and Weston NHS Foundation Trust: collaborator
• Manchester University NHS Foundation Trust: collaborator
• Northern Care Alliance NHS Foundation Trust: collaborator
• University Hospital Southampton NHS Foundation Trust: collaborator
• Newcastle-upon-Tyne Hospitals NHS Trust: collaborator
• Nottingham University Hospitals NHS Trust: collaborator
• NHS Lothian: collaborator

Study Sites (18)

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

Location

North Bristol NHS Trust

Bristol, United Kingdom

Location

University Hospital Bristol NHS Foundation Trust

Bristol, United Kingdom

Location

Cardiff and Vale University Health Board

Cardiff, United Kingdom

Location

NHS Lothian

Edinburgh, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, United Kingdom

Location

Walton Centre NHS Foundation Trust

Liverpool, United Kingdom

Location

Great Ormond Street Children's Hospital

London, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, United Kingdom

Location

University of London and Bart's Health NHS Trust

London, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust

Manchester, United Kingdom

Location

Newcastle-upon-Tyne Hospitals NHS Trust

Newcastle, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Location

University Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 28639937 DERIVED

• 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.

  PMID: 26009577 DERIVED

MeSH Terms

Conditions

Myelitis, Transverse; Neuromyelitis Optica

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Central Nervous System Diseases; Spinal Cord Diseases; Demyelinating Diseases; Neurodegenerative Diseases; Neuroinflammatory Diseases; Autoimmune Diseases; Immune System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ming Lim, MB, PhD

  Guy's and St Thomas' NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: March 26, 2015
• Study Start: March 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: July 20, 2016

Record last verified: 2016-07

Locations

GB (18)