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

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ClinicalTrials.gov Identifier: NCT02398994
Recruitment Status : Terminated (Continued effort did not successfully increase recruitment into the study.)
First Posted : March 26, 2015
Last Update Posted : July 20, 2016
Sponsor:
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 NHS Foundation Trust
Manchester University NHS Foundation Trust
Salford Royal NHS Foundation Trust
University Hospital Southampton NHS Foundation Trust
Newcastle-upon-Tyne Hospitals NHS Trust
Nottingham University Hospitals NHS Trust
NHS Lothian
Information provided by (Responsible Party):
Guy's and St Thomas' NHS Foundation Trust

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.


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Study Type : Interventional  (Clinical Trial)
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 : March 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016


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



Primary Outcome Measures :
  1. 2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E) [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112) [ Time Frame: 6 months ]
  2. Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring [ Time Frame: 6 months ]
  3. EQ-5D-Y (for patients aged 8-12 years at presentation) [ Time Frame: 6 months ]
  4. EQ-5D-5L (for patients aged 13 years or over at presentation) [ Time Frame: 6 months ]
  5. International Spinal Cord Injury (SCI) Quality of Life Basic Data Set (for patients aged 13 years or over at presentation) [ Time Frame: 6 months ]
  6. Client Service Receipt Inventory (CSRI) [ Time Frame: 6 months ]

Other Outcome Measures:
  1. International SCI Bladder/Bowel Data Set (for patients aged 13 years or over at presentation) [ Time Frame: 6 months ]
  2. Paediatric Quality of Life Inventory™ (PedsQL) Parent Report for Toddlers (for patients aged 2-4 years at presentation) [ Time Frame: 6 months ]
  3. Paediatric Quality of Life Inventory™(PedsQL) Parent Report for Young Children (for patients aged 5-7 years at presentation) [ Time Frame: 6 months ]
  4. International SCI Pain Basic Data Set (for patients ages 13 years or over at presentation) [ Time Frame: 6 months ]


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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02398994


Locations
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United Kingdom
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
North Bristol NHS Trust
Bristol, United Kingdom
University Hospital Bristol NHS Foundation Trust
Bristol, United Kingdom
Cardiff and Vale University Health Board
Cardiff, United Kingdom
NHS Lothian
Edinburgh, United Kingdom
Alder Hey Children's NHS Foundation Trust
Liverpool, United Kingdom
Walton Centre NHS Foundation Trust
Liverpool, United Kingdom
Great Ormond Street Children's Hospital
London, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom
University of London and Bart's Health NHS Trust
London, United Kingdom
Central Manchester University Hospitals NHS Foundation Trust
Manchester, United Kingdom
Newcastle-upon-Tyne Hospitals NHS Trust
Newcastle, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Oxford University Hospitals NHS Trust
Oxford, United Kingdom
Salford Royal NHS Foundation Trust
Salford, United Kingdom
University Southampton NHS Foundation Trust
Southampton, United Kingdom
Sponsors and Collaborators
Guy's and St Thomas' NHS Foundation Trust
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 NHS Foundation Trust
Manchester University NHS Foundation Trust
Salford Royal NHS Foundation Trust
University Hospital Southampton NHS Foundation Trust
Newcastle-upon-Tyne Hospitals NHS Trust
Nottingham University Hospitals NHS Trust
NHS Lothian
Investigators
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Principal Investigator: Ming Lim, MB, PhD Guy's and St Thomas' NHS Foundation Trust

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02398994     History of Changes
Other Study ID Numbers: RJ115/N065
2014-002335-34 ( EudraCT Number )
11/129/148 ( Other Grant/Funding Number: National Institute for Health Research, Health Technology )
12127581 ( Other Identifier: ISRCTN )
First Posted: March 26, 2015    Key Record Dates
Last Update Posted: July 20, 2016
Last Verified: July 2016

Keywords provided by Guy's and St Thomas' NHS Foundation Trust:
Clinical Trials Unit
Pediatric

Additional relevant MeSH terms:
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Myelitis, Transverse
Neuromyelitis Optica
Myelitis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases
Central Nervous System Infections
Central Nervous System Diseases
Spinal Cord Diseases
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Paraneoplastic Syndromes
Neurodegenerative Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Immunoglobulins