High Dose Steroids in Children With Stroke (PASTA)

  • STATUS
    Recruiting
  • End date
    Jul 12, 2025
  • participants needed
    70
  • sponsor
    University Hospital Inselspital, Berne
Updated on 12 March 2022

Summary

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.

Description

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 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

Study duration: 48 months

Study Centre(s): International multi-centre study with approximately 20 to 30 centres

Participating countries:Switzerland, Germany, France, Austria, Great Britain & Australia

Centres in additional countries might be considered.

Statistical Considerations: The sample size is based on the comparison of the primary outcome

  • the change in FCASS from baseline to 1 month - between the two treatment groups. The standard deviation from 13 patients of a retrospective study was calculated. The standard deviation of the baseline and follow-up FCASS was 3.0 and 3.3, respectively. The standard deviation of the change in FCASS from baseline was 2.8. Based on the standard deviation of 2.8 and a two-sample means test, 64 patients (32 in each group) are required to detect a difference of 2.0 with a power of 80% at a two-sided alpha-level of 0.05. To account for dropouts (8%), we enlarge the sample size to 70 patients (35 in each group). The primary analysis will follow the intention-to-treat (ITT) principle, i.e. all patients will be analysed in the allocated group regardless of any protocol violations such as cross-overs. The primary outcome (change in FCASS from baseline to 1 month) as well as other secondary continuous score outcomes that are measured multiple times during follow-up (RRQ, mRS, PSOM, VABS, modAspect) will be assessed in a repeated-measure, mixed-effects linear model.

GCP Statement: This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, ICH-GCP as well as all national legal and regulatory requirements.

Details
Condition Pediatric ALL
Treatment Methylprednisolone, Prednisolone
Clinical Study IdentifierNCT04873583
SponsorUniversity Hospital Inselspital, Berne
Last Modified on12 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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)
Female participants age ≥ 13: Negative pregnancy test (blood)

Exclusion Criteria

Previous stroke
Known syndromal disorders, as e.g. Trisomy 21, Neurofibromatosis type 1
Known genetic vasculopathies as e.g. PHACES syndrome, 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
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