A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin (IVIg) Versus Standard Therapy for the Treatment of Transverse Myelitis in Adults and Children
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 18
- 主要终点
- 2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Intravenous Methylprednisolone (Drug)
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.
干预措施: Intravenous Methylprednisolone (Drug)
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.
干预措施: Intravenous Immunoglobulin (Drug)
结局指标
主要结局
2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E)
时间窗: 6 months
次要结局
- Client Service Receipt Inventory (CSRI)(6 months)
- Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring(6 months)
- Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112)(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)
- EQ-5D-Y (for patients aged 8-12 years at presentation)(6 months)