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

A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin (IVIg) Versus Standard Therapy for the Treatment of Transverse Myelitis in Adults and Children

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.

Study Overview

• Status: Terminated
• Conditions: Neuromyelitis Optica; Myelitis, Transverse
• Intervention / Treatment: Drug: Intravenous Methylprednisolone; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E)	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• TM Society Trial Information
• National Institute for Health Research Portfolio

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: March 23, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimate): March 26, 2015

Study Record Updates

• Last Update Posted (Estimate): July 20, 2016
• Last Update Submitted That Met QC Criteria: July 18, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Pediatric; Clinical Trials Unit
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Immune System Diseases; Neoplasms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neoplasms by Site; Eye Diseases; Central Nervous System Infections; Neurodegenerative Diseases; Spinal Cord Diseases; Nervous System Neoplasms; Optic Nerve Diseases; Cranial Nerve Diseases; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Optic Neuritis; Neuromyelitis Optica; Myelitis; Myelitis, Transverse; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Methylprednisolone; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• 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)