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

Sponsor

Guy's and St Thomas' NHS Foundation Trust (Other)

Overall Status

Terminated

CT.gov ID

NCT02398994

Collaborator

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

Enrollment

Locations

Arms

Duration (Months)

0.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelitis, Transverse Neuromyelitis Optica	Drug: Intravenous Methylprednisolone Drug: Intravenous Immunoglobulin	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2015

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Intravenous Methylprednisolone
Experimental: 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.	Drug: Intravenous Methylprednisolone Drug: Intravenous Immunoglobulin

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: Intravenous Methylprednisolone

Experimental: 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.

Drug: Intravenous Methylprednisolone

Drug: Intravenous Immunoglobulin

Outcome Measures

Primary Outcome Measures

2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E) [6 months]

Secondary Outcome Measures

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]
Client Service Receipt Inventory (CSRI) [6 months]

Other Outcome Measures

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]
International SCI Pain Basic Data Set (for patients ages 13 years or over at presentation) [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Birmingham Children's Hospital NHS Foundation Trust	Birmingham	United Kingdom
2	University Hospitals Birmingham NHS Foundation Trust	Birmingham	United Kingdom
3	North Bristol NHS Trust	Bristol	United Kingdom
4	University Hospital Bristol NHS Foundation Trust	Bristol	United Kingdom
5	Cardiff and Vale University Health Board	Cardiff	United Kingdom
6	NHS Lothian	Edinburgh	United Kingdom
7	Alder Hey Children's NHS Foundation Trust	Liverpool	United Kingdom
8	Walton Centre NHS Foundation Trust	Liverpool	United Kingdom
9	Great Ormond Street Children's Hospital	London	United Kingdom
10	Guy's and St Thomas' NHS Foundation Trust	London	United Kingdom
11	King's College Hospital NHS Foundation Trust	London	United Kingdom
12	University of London and Bart's Health NHS Trust	London	United Kingdom
13	Central Manchester University Hospitals NHS Foundation Trust	Manchester	United Kingdom
14	Newcastle-upon-Tyne Hospitals NHS Trust	Newcastle	United Kingdom
15	Nottingham University Hospitals NHS Trust	Nottingham	United Kingdom
16	Oxford University Hospitals NHS Trust	Oxford	United Kingdom
17	Salford Royal NHS Foundation Trust	Salford	United Kingdom
18	University Southampton NHS Foundation Trust	Southampton	United Kingdom