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

NCT ID: NCT02398994

Last Updated: 2016-07-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-31

Study Completion Date

2016-03-31

Brief Summary

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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

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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.

Conditions

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Myelitis, Transverse Neuromyelitis Optica

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Intravenous Methylprednisolone

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.

Group Type ACTIVE_COMPARATOR

Intravenous Methylprednisolone

Intervention Type DRUG

Intravenous Immunoglobulin

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.

Group Type EXPERIMENTAL

Intravenous Methylprednisolone

Intervention Type DRUG

Intravenous Immunoglobulin

Intervention Type DRUG

Interventions

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Intravenous Methylprednisolone

Intervention Type DRUG

Intravenous Immunoglobulin

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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King's College London

OTHER

Sponsor Role collaborator

Barts and the London School of Medicine and Dentistry

OTHER

Sponsor Role collaborator

Cardiff University

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role collaborator

Barts & The London NHS Trust

OTHER

Sponsor Role collaborator

Alder Hey Children's NHS Foundation Trust

OTHER

Sponsor Role collaborator

Walton Centre NHS Foundation Trust

OTHER

Sponsor Role collaborator

Oxford University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Birmingham Women's and Children's NHS Foundation Trust

OTHER

Sponsor Role collaborator

University Hospital Birmingham NHS Foundation Trust

OTHER

Sponsor Role collaborator

Cardiff and Vale University Health Board

OTHER_GOV

Sponsor Role collaborator

North Bristol NHS Trust

OTHER

Sponsor Role collaborator

University Hospitals Bristol and Weston NHS Foundation Trust

OTHER

Sponsor Role collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

Northern Care Alliance NHS Foundation Trust

OTHER

Sponsor Role collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role collaborator

Newcastle-upon-Tyne Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Nottingham University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

NHS Lothian

OTHER_GOV

Sponsor Role collaborator

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ming Lim, MB, PhD

Role: PRINCIPAL_INVESTIGATOR

Guy's and St Thomas' NHS Foundation Trust

Locations

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Birmingham Children's Hospital NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

North Bristol NHS Trust

Bristol, , United Kingdom

Site Status

University Hospital Bristol NHS Foundation Trust

Bristol, , United Kingdom

Site Status

Cardiff and Vale University Health Board

Cardiff, , United Kingdom

Site Status

NHS Lothian

Edinburgh, , United Kingdom

Site Status

Alder Hey Children's NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Walton Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Great Ormond Street Children's Hospital

London, , United Kingdom

Site Status

Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status

King's College Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

University of London and Bart's Health NHS Trust

London, , United Kingdom

Site Status

Central Manchester University Hospitals NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Newcastle-upon-Tyne Hospitals NHS Trust

Newcastle, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

Oxford University Hospitals NHS Trust

Oxford, , United Kingdom

Site Status

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Site Status

University Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 28639937 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26009577 (View on PubMed)

Other Identifiers

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2014-002335-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

11/129/148

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

12127581

Identifier Type: OTHER

Identifier Source: secondary_id

RJ115/N065

Identifier Type: -

Identifier Source: org_study_id

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