High Dose Steroids in Children with Stroke and Unilateral Focal Arteriopathy: A Multicenter Randomized Controlled Trial

Rationale
Focal cerebral arteriopathy (FCA), a unilateral, monophasic disease of the intracranial arteries, is one of the most common etiologies of pediatric stroke. Imaging and laboratory evidence suggest an underlying inflammatory mechanism. The arteriopathy can progress over days to weeks, conferring a high risk of additional ischemic brain injury. Given its presumed inflammatory origin, there has been recently an emerging trend to intervene with corticosteroid treatment. However, there is a paucity of evidence on whether steroid treatment improves outcomes.

Aim
The aim of this study is to investigate whether high dose corticosteroids result in greater and faster improvement of focal stenosis in children with stroke and FCA and how this intervention influences neurological and neuropsychological outcomes as well as quality of life.

Sample size estimates
A sample size of 64 patients assigned 1:1 to the two study arms is required to detect a clinically relevant difference of 2.0 in the primary outcome with a power of 80% at a two-sided alpha-level of 0.05.

Methods and design
This is a Prospective Randomized Open, Blinded Endpoint (PROBE) study involving 27 centers in Europe and Australia. Patients between 6 months and 18 years with a unilateral arteriopathy will be enrolled during a recruitment period of 3 years. A total of 70 participants (accounting for 8% dropouts) will be centrally randomized to standard care (including aspirin) alone or standard care plus high-dose-corticosteroids (experimental arm) in a ratio 1:1.

Study outcomes
The primary outcome measure is change in Magnetic resonance imaging (MRI) based FCA Severity Score (FCASS) from baseline to 1 month, compared between the two study arms. In addition, the study comprises various clinical and imaging-based information as well as analyses of adverse reactions.

Discussion
This will be one of the first prospective treatment trials in the field of pediatric stroke. The preparation for the study has already impacted stroke care of children worldwide through development of international collaborative trial networks and standardized neuroimaging based vascular scoring system.