High Dose Steroids in Children With Stroke and Unilateral Focal Arteriopathy: A Multicentre Randomized Controlled Trial PASTA (Paediatric Arteriopathy Steroid Aspirin) Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 35
- 主要终点
- Change in Focal Cerebral Arteriopathy Severity Score (FCASS) from baseline
研究概览
简要总结
This clinical trial deals with focal cerebral arteriopathy and childhood stroke, a rare but devastating condition.
Focal cerebral arteriopathy (FCA) is an inflammatory vessel wall disease provoked by infection and there is increasing evidence that inflammatory processes play a crucial role in childhood stroke, influencing the outcome of the disease.
Analysis of existing data suggests that outcomes are improved and that there is less stroke recurrence in children treated with steroids to reduce the acute inflammatory processes. This clinical trial will be conducted in over 20 hospitals in several countries in order to investigate this.
Participants will be randomly separated into two groups. The first group will be treated with standard of care (including aspirin) combined with high dose steroids. The second group will be treated with standard of care (including aspirin) but without steroid treatment.
The objective is to investigate if children treated with a combination of high dose steroid and aspirin will have a better and quicker recovery of FCA, better clinical functional outcome, and less recurrence compared to children treated with aspirin alone.
This project has been identified by international pediatric stroke experts as the most important topic for a clinical trial in the field and is as well one of the most important research priorities identified by parents. The study results will also provide insight into the evolution of inflammatory vessel disease.
详细描述
Background: Arterial ischemic stroke (AIS) is a rare but devastating condition affecting 2-5/100,000 children/year. Children do not recover better than adults with 2/3 suffering long term neurological, cognitive and behavioural problems. The economic cost of stroke is substantial. Arteriopathy is identified as AIS aetiology in 60-80% of previously healthy children and is the strongest predictor of recurrent events. 30-40% of these children will have a focal cerebral arteriopathy (FCA). FCA in childhood is shown to be an inflammatory vessel wall pathology provoked by infections. This encourages treatment with steroids, despite lack of evidence.
Rationale: There is increasing evidence that etiologically inflammatory processes play a crucial role in childhood stroke, and influence outcome. Retrospective analyses suggest improved outcome and less recurrence with steroid treatment. With the exception of sickle cell disease, this study will be the first randomized clinical trial in children with arterial ischemic stroke. It will provide high-level evidence for the most appropriate treatment for children with AIS due to FCA. Alignment of interventions and outcome as well as pooled analysis with the planned Focal Cerebral Arteriopathy Steroid (FOCAS) study in North America will allow pooled analysis results.This is very important in view of the marked neurological, social and economic burden of childhood AIS for patients and families. This project has been identified as the most important AIS treatment trial by a Delphi survey of international paediatric stroke experts and is one of the most important research priorities identified by parents. In addition, the study will provide insights into the pathogenesis of inflammatory vasculopathies.The objective of this trial is to show that children with first stroke event due to unilateral FCA treated with a combination of high dose steroid and aspirin will have better and quicker recovery of arteriopathy, better clinical functional outcome, and less recurrence compared to children treated with aspirin alone.
The proposed study is a prospective multicentre, parallel group, two-arm, randomized controlled, open-label clinical trial with blinded outcome assessment, comparing a high dose course of methylprednisolone / prednisolone plus standard of care with standard of care alone in children with unilateral arteriopathy and acute ischemic stroke.
Measurements and procedures: Participants will be randomized within 48 hours after diagnosis (maximum 96 hours after stroke onset) to standard of care (SC) alone (control group) or SC plus steroids (experimental group). SC will be harmonized among the study centres to include aspirin treatment. Patients will be assessed at 1, 3, 6 and 12 months. Magnetic imaging and angiography (MRI/MRA) will be done at 1, (3) and 6 months.
Number of Participants: 70 participants in total, 35 per treatment arm
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
- 6 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent of the legal representative of the trial participant documented by signature
- •Age > 6 months & < 18 years at time of stroke
- •Randomisation possible within 48 hours of diagnosis and maximum 96 hours after stroke onset
- •Unilateral arteriopathy according to the following criteria:
- •Newly acquired neurologic deficits
- •Specific neuroimaging (MRA) features of either
- •unilateral stenosis, or
- •unilateral vessel irregularities within the Central Nervous System (CNS)
- •Unless otherwise defined in the national addendum: Female participants age ≥ 13: Negative pregnancy test (blood or urine)
排除标准
- •Previous stroke
- •Known syndromal disorders, as e.g. Trisomy 21, Neurofibromatosis type 1
- •Known genetic vasculopathies as e.g. posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies and eye anomalies syndrome (PHACES), actin alpha 2 (ACTA II)
- •Moyamoya or sickle cell disease
- •Small vessel cerebral vasculitis (primary CNS vasculitis)
- •Bilateral arteriopathy
- •Arterial dissection(s)
- •Evidence of underlying systemic disorders, as e.g. lupus, rheumatoid problems
- •Secondary CNS angiitis due to infections (meningitis, endocarditis, borreliosis), or generalised angiitis due to rheumatic or other autoimmune problems
- •Progressive large to medium childhood primary angiitis of the CNS (cPACNS ) with 2 of the following 3 criteria:
- •pre-existing progressive neurocognitive dysfunction
- •bilateral MRI lesions/vessel involvement
- •small vessel arterial stenosis
- •On steroid treatment at disease onset
- •Contraindication to steroid treatment as e.g. a congenital or acquired immunodeficiency
- •Inability to follow the procedures of the study, e.g. due to language problems
- •Participation in another interventional study within the 30 days preceding the indication stroke and during the present study
研究组 & 干预措施
Steroids + Standard of care
Standard of care (including aspirin) and intravenous steroids, followed by oral tapering.
干预措施: Methylprednisolone (Drug)
Steroids + Standard of care
Standard of care (including aspirin) and intravenous steroids, followed by oral tapering.
干预措施: Prednisolone (Drug)
结局指标
主要结局
Change in Focal Cerebral Arteriopathy Severity Score (FCASS) from baseline
时间窗: 1 month (30 days)
The FCASS is a scaling system that has been developed to improve diagnostic criteria and to better document the typical course of initial worsening followed by improvement in FCA-i (focal cerebral arteriopathy of inflammatory type). FCASS Minimum score (best outcome): 0 FCASS Maximum baseline score (worst outcome): 20 FCASS Maximum follow up score (worst outcome): 21
次要结局
- Degree of disability or dependence by modified Rankin Scale (mRS)(1, 3, 6, and 12 months)
- Clinical outcome by Vineland adaptive behavior scale (VABS)(6 and 12 months)
- Change in FCASS (Focal Cerebral Arteriopathy Severity Score) from baseline(6 months)
- Functional impairment outcome measured by Pediatric Stroke Outcome Measure (PSOM)(1, 3, 6 and 12 months)
- Preschool Wechsler Intelligence Scale for Children (WISC V) / Wechsler Preschool and Primary Scale of Intelligence (WIPPSI IV)(12 month)
- Delis-Kaplan Executive Function System (D-KEFS)(12 month)
- Recovery assessed by Recovery and Recurrence Questionnaire (RRQ)(1, 3, 6, and 12 months)
- Volume of stroke(baseline, 1, 3 (if imaging is available) and 6 months)
- Residual vasculopathy(6 months)
- Stroke recurrence after index stroke(1, 6 and 12 months)
- Stroke recurrence after index stroke in relation to the initial degree of vessel stenosis(6 and 12 months)
- Stroke Quality of Life Measure (PSQLM)(12 month)
- Continuous performance task (CPT-III)(12 month)