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

Neuromyelitis Optica Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02398994
• Other study ID #: RJ115/N065
• Secondary ID: 2014-002335-3411
• Status: Terminated
• Phase: Phase 3
• First received: March 23, 2015
• Last updated: July 18, 2016
• Start date: March 2015
• Est. completion date: March 2016

Study information

• Verified date: July 2016
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Institute for Health ResearchUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelitis
• Myelitis, Transverse
• Neuromyelitis Optica

Intervention

Drug:
• Intravenous Methylprednisolone

• Intravenous Immunoglobulin

Locations

Country	Name	City	State
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

Sponsors (22)

Lead Sponsor

Collaborator

Guy's and St Thomas' NHS Foundation Trust

Alder Hey Children's NHS Foundation Trust, Barts & The London NHS Trust, Barts and the London School of Medicine and Dentistry, Birmingham Children's Hospital NHS Foundation Trust, Cardiff and Vale University Health Board, Cardiff University, Central Manchester University Hospitals NHS Foundation Trust, Great Ormond Street Hospital for Children NHS Foundation Trust, King's College Hospital NHS Trust, King's College London, Newcastle-upon-Tyne Hospitals NHS Trust, NHS Lothian, North Bristol NHS Trust, Nottingham University Hospitals NHS Trust, Oxford University Hospitals NHS Trust, Salford Royal NHS Foundation Trust, University College, London, University Hospital Birmingham NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust., University Hospitals Bristol NHS Foundation Trust, Walton Centre NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	International SCI Bladder/Bowel Data Set (for patients aged 13 years or over at presentation)		6 months	No
Other	Paediatric Quality of Life Inventory™ (PedsQL) Parent Report for Toddlers (for patients aged 2-4 years at presentation)		6 months	No
Other	Paediatric Quality of Life Inventory™(PedsQL) Parent Report for Young Children (for patients aged 5-7 years at presentation)		6 months	No
Other	International SCI Pain Basic Data Set (for patients ages 13 years or over at presentation)		6 months	No
Primary	2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E)		6 months	No
Secondary	Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112)		6 months	No
Secondary	Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring		6 months	No
Secondary	EQ-5D-Y (for patients aged 8-12 years at presentation)		6 months	No
Secondary	EQ-5D-5L (for patients aged 13 years or over at presentation)		6 months	No
Secondary	International Spinal Cord Injury (SCI) Quality of Life Basic Data Set (for patients aged 13 years or over at presentation)		6 months	No
Secondary	Client Service Receipt Inventory (CSRI)		6 months	No

External Links

•   National Institute for Health Research Portfolio
•   STRIVE Public Website
•   TM Society Trial Information
•   United Kingdom Clinical Research Network Database