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

Primary Purpose

Myelitis, Transverse, Neuromyelitis Optica

Status
Terminated
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Intravenous Methylprednisolone
Intravenous Immunoglobulin
Sponsored by
Guy's and St Thomas' NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelitis, Transverse focused on measuring Clinical Trials Unit, Pediatric

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Birmingham Children's Hospital NHS Foundation Trust
  • University Hospitals Birmingham NHS Foundation Trust
  • North Bristol NHS Trust
  • University Hospital Bristol NHS Foundation Trust
  • Cardiff and Vale University Health Board
  • NHS Lothian
  • Alder Hey Children's NHS Foundation Trust
  • Walton Centre NHS Foundation Trust
  • Great Ormond Street Children's Hospital
  • Guy's and St Thomas' NHS Foundation Trust
  • King's College Hospital NHS Foundation Trust
  • University of London and Bart's Health NHS Trust
  • Central Manchester University Hospitals NHS Foundation Trust
  • Newcastle-upon-Tyne Hospitals NHS Trust
  • Nottingham University Hospitals NHS Trust
  • Oxford University Hospitals NHS Trust
  • Salford Royal NHS Foundation Trust
  • University Southampton NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Intravenous Methylprednisolone

Intravenous Immunoglobulin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112)
Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring
EQ-5D-Y (for patients aged 8-12 years at presentation)
EQ-5D-5L (for patients aged 13 years or over at presentation)
International Spinal Cord Injury (SCI) Quality of Life Basic Data Set (for patients aged 13 years or over at presentation)
Client Service Receipt Inventory (CSRI)

Full Information

First Posted
March 23, 2015
Last Updated
July 18, 2016
Sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborators
King's College London, Barts and the London School of Medicine and Dentistry, Cardiff University, University College, London, King's College Hospital NHS Trust, Great Ormond Street Hospital for Children NHS Foundation Trust, Barts & The London NHS Trust, Alder Hey Children's NHS Foundation Trust, Walton Centre NHS Foundation Trust, Oxford University Hospitals NHS Trust, Birmingham Women's and Children's NHS Foundation Trust, University Hospital Birmingham NHS Foundation Trust, Cardiff and Vale University Health Board, North Bristol NHS Trust, University Hospitals Bristol and Weston NHS Foundation Trust, Manchester University NHS Foundation Trust, Northern Care Alliance NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust, Newcastle-upon-Tyne Hospitals NHS Trust, Nottingham University Hospitals NHS Trust, NHS Lothian
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1. Study Identification

Unique Protocol Identification Number
NCT02398994
Brief Title
A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis
Acronym
STRIVE
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

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Terminated
Why Stopped
Continued effort did not successfully increase recruitment into the study.
Study Start Date
March 2015 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelitis, Transverse, Neuromyelitis Optica
Keywords
Clinical Trials Unit, Pediatric

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intravenous Methylprednisolone
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Intravenous Immunoglobulin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Intravenous Methylprednisolone
Intervention Type
Drug
Intervention Name(s)
Intravenous Immunoglobulin
Primary Outcome Measure Information:
Title
2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112)
Time Frame
6 months
Title
Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring
Time Frame
6 months
Title
EQ-5D-Y (for patients aged 8-12 years at presentation)
Time Frame
6 months
Title
EQ-5D-5L (for patients aged 13 years or over at presentation)
Time Frame
6 months
Title
International Spinal Cord Injury (SCI) Quality of Life Basic Data Set (for patients aged 13 years or over at presentation)
Time Frame
6 months
Title
Client Service Receipt Inventory (CSRI)
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
International SCI Bladder/Bowel Data Set (for patients aged 13 years or over at presentation)
Time Frame
6 months
Title
Paediatric Quality of Life Inventory™ (PedsQL) Parent Report for Toddlers (for patients aged 2-4 years at presentation)
Time Frame
6 months
Title
Paediatric Quality of Life Inventory™(PedsQL) Parent Report for Young Children (for patients aged 5-7 years at presentation)
Time Frame
6 months
Title
International SCI Pain Basic Data Set (for patients ages 13 years or over at presentation)
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ming Lim, MB, PhD
Organizational Affiliation
Guy's and St Thomas' NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Birmingham Children's Hospital NHS Foundation Trust
City
Birmingham
Country
United Kingdom
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
Country
United Kingdom
Facility Name
North Bristol NHS Trust
City
Bristol
Country
United Kingdom
Facility Name
University Hospital Bristol NHS Foundation Trust
City
Bristol
Country
United Kingdom
Facility Name
Cardiff and Vale University Health Board
City
Cardiff
Country
United Kingdom
Facility Name
NHS Lothian
City
Edinburgh
Country
United Kingdom
Facility Name
Alder Hey Children's NHS Foundation Trust
City
Liverpool
Country
United Kingdom
Facility Name
Walton Centre NHS Foundation Trust
City
Liverpool
Country
United Kingdom
Facility Name
Great Ormond Street Children's Hospital
City
London
Country
United Kingdom
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
King's College Hospital NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
University of London and Bart's Health NHS Trust
City
London
Country
United Kingdom
Facility Name
Central Manchester University Hospitals NHS Foundation Trust
City
Manchester
Country
United Kingdom
Facility Name
Newcastle-upon-Tyne Hospitals NHS Trust
City
Newcastle
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
Country
United Kingdom
Facility Name
Oxford University Hospitals NHS Trust
City
Oxford
Country
United Kingdom
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
Country
United Kingdom
Facility Name
University Southampton NHS Foundation Trust
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28639937
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.
Results Reference
derived
PubMed Identifier
26009577
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.
Results Reference
derived
Links:
URL
http://www.myelitis.org.uk/strive-clinical-trial.html
Description
TM Society Trial Information
URL
http://www.nets.nihr.ac.uk/projects/hta/11129148
Description
National Institute for Health Research Portfolio

Learn more about this trial

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

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