High Dose Steroids in Children With Stroke

NCT ID: NCT04873583

Last Updated: 2025-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-16

Study Completion Date

2026-07-31

Brief Summary

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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.

Detailed Description

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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

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, Pediatric Stroke Outcome Measure (PSOM), VABS, modAspect) will be assessed in a repeated-measure, mixed-effects linear model.

Good Clinical Practice (GCP) Statement: This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH-GCP) as well as all national legal and regulatory requirements.

Conditions

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Paediatric Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multi-center, randomized, controlled, non-blinded trial
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Steroids + Standard of care

Standard of care (including aspirin) and intravenous steroids, followed by oral tapering.

Group Type EXPERIMENTAL

Methylprednisolone

Intervention Type DRUG

At the time of inclusion, intravenous Methylprednisolone for 3 days. Dose: 30 mg/kg/day (max. 1000 mg/dose)

Prednisolone

Intervention Type DRUG

Intravenous treatment will be immediately followed by oral tapering with Prednisolone.

Oral Prednisolone, 2 weeks (week 1 and 2) Dose: 1 mg/kg/day (max 40 mg/day) Oral Prednisolone, 2 weeks (week 3 and 4) Dose: 0.5 mg/kg/day (max 20 mg/day)

Standard of care

Standard of care (including aspirin)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Methylprednisolone

At the time of inclusion, intravenous Methylprednisolone for 3 days. Dose: 30 mg/kg/day (max. 1000 mg/dose)

Intervention Type DRUG

Prednisolone

Intravenous treatment will be immediately followed by oral tapering with Prednisolone.

Oral Prednisolone, 2 weeks (week 1 and 2) Dose: 1 mg/kg/day (max 40 mg/day) Oral Prednisolone, 2 weeks (week 3 and 4) Dose: 0.5 mg/kg/day (max 20 mg/day)

Intervention Type DRUG

Other Intervention Names

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Solu-Medrol Spiricort

Eligibility Criteria

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Inclusion Criteria

1. Informed consent of the legal representative of the trial participant documented by signature
2. Age \> 6 months \& \< 18 years at time of stroke
3. Randomisation possible within 48 hours of diagnosis and maximum 96 hours after stroke onset
4. 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)
5. Unless otherwise defined in the national addendum: Female participants age ≥ 13: Negative pregnancy test (blood or urine)

Exclusion Criteria

1. Previous stroke
2. Known syndromal disorders, as e.g. Trisomy 21, Neurofibromatosis type 1
3. Known genetic vasculopathies as e.g. posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies and eye anomalies syndrome (PHACES), actin alpha 2 (ACTA II)
4. Moyamoya or sickle cell disease
5. Small vessel cerebral vasculitis (primary CNS vasculitis)
6. Bilateral arteriopathy
7. Arterial dissection(s)
8. Evidence of underlying systemic disorders, as e.g. lupus, rheumatoid problems
9. Secondary CNS angiitis due to infections (meningitis, endocarditis, borreliosis), or generalised angiitis due to rheumatic or other autoimmune problems
10. Progressive large to medium childhood primary angiitis of the CNS (cPACNS ) with 2 of the following 3 criteria:

1. pre-existing progressive neurocognitive dysfunction
2. bilateral MRI lesions/vessel involvement
3. small vessel arterial stenosis
11. On steroid treatment at disease onset
12. Contraindication to steroid treatment as e.g. a congenital or acquired immunodeficiency
13. Inability to follow the procedures of the study, e.g. due to language problems
14. Participation in another interventional study within the 30 days preceding the indication stroke and during the present study
Minimum Eligible Age

6 Months

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bern

OTHER

Sponsor Role collaborator

LUMIS International GmbH

UNKNOWN

Sponsor Role collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maja Steinlin, Prof. em. Dr. med.

Role: STUDY_DIRECTOR

Bern university hospital, Inselspital Bern, Kinderklinik

Locations

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Sydney Childrens Hospital Randwick

Randwick, New South Wales, Australia

Site Status RECRUITING

Sydney Childrens Hospital Network

Westmead, New South Wales, Australia

Site Status RECRUITING

Melbourne Childrens Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

Universitätsklinik für Pädiatrie 1 A.ö. Landeskrankenhaus/ Universitätskliniken Innsbruck

Innsbruck, Tyrol, Austria

Site Status NOT_YET_RECRUITING

Johannes Kepler University Linz, Med Campus IV, Univ.-Klinik für Kinder- und Jugendheilkunde

Linz, Upper Austria, Austria

Site Status NOT_YET_RECRUITING

Universitätsklinik für Kinder und Jugendheilkunde Wien

Vienna, , Austria

Site Status RECRUITING

Børn og Unge - Aarhus Universitetshospital

Aarhus, , Denmark

Site Status NOT_YET_RECRUITING

Department of Pediatric and Adolescence Medicine Copenhagen University Hospital

Copenhagen, , Denmark

Site Status RECRUITING

L'ASSISTANCE PUBLIQUE-HOPITAUX DE MARSEILLE (AP-HM) - Hôpital de la Timone

Marseille, Aix-en-Provence, France

Site Status RECRUITING

Pediatric Neurology Strasbourg - Hautepierre University Hospital

Strasbourg, Alsace, France

Site Status RECRUITING

Hôpital Femme Mère Enfant Lyon

Bron, Auvergne-Rhône-Alpes, France

Site Status RECRUITING

Hôpital Roger Salengro, CHRU de Lille

Lille, , France

Site Status RECRUITING

Hôpitaux Universitaires Paris Sud

Le Kremlin-Bicêtre, Île-de-France Region, France

Site Status RECRUITING

Hôpital Necker-Enfants Malades

Paris, Île-de-France Region, France

Site Status RECRUITING

Universitätsklinikum Freiburg Zentrum für Kinder- und Jugendmedizin Klinik für Neuropädiatrie und Muskelerkrankungen

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status RECRUITING

LMU Klinikum

München, Bavaria, Germany

Site Status RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, Nordrhein-Westfahlen, Germany

Site Status RECRUITING

Universitäts Kinderklinik Münster

Münster, Nordrhein-Westfahlen, Germany

Site Status RECRUITING

Charité-Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover OE 6720

Hanover, , Germany

Site Status RECRUITING

Centrum för Kliniska Barnstudier, Astrid Lindgrens Bansjukhus, Kaolinska Universitetssjukhuset

Stockholm, , Sweden

Site Status NOT_YET_RECRUITING

Centre Hôpitalier Universitaire Vaud (CHUV), Unité de Neurologie

Lausanne, Canton of Vaud, Switzerland

Site Status RECRUITING

Ospedale Regionale di Bellinzona e Valli

Bellinzona, Canton Ticino, Switzerland

Site Status RECRUITING

Kantonsspital Graubünden, Departement Kinder- und Jugendmedizin

Chur, Kanton Graubünden, Switzerland

Site Status RECRUITING

Hôpital du Valais

Sion, Valais, Switzerland

Site Status RECRUITING

Universitätskinderklinik beider Basel

Basel, , Switzerland

Site Status RECRUITING

Inselspital Bern

Bern, , Switzerland

Site Status RECRUITING

Hôpitale Universitaire de Genève, Neuropediatrie, Hôpital des Enfants

Geneva, , Switzerland

Site Status RECRUITING

Luzerner Kantonsspital, Kinderspital, Neuropädiatrie

Lucerne, , Switzerland

Site Status ACTIVE_NOT_RECRUITING

Stiftung ostschweizerisches Kinderspital

Sankt Gallen, , Switzerland

Site Status RECRUITING

Kidnerspital Zürich

Zurich, , Switzerland

Site Status RECRUITING

Addenbrookes Hospital - Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, United Kingdom

Site Status RECRUITING

University Hospital Southampton

Southampton, Hampshire, United Kingdom

Site Status RECRUITING

Royal Manchester Children's Hospital

Manchester, Lancashire, United Kingdom

Site Status RECRUITING

University Hospital Bristol

Bristol, , United Kingdom

Site Status RECRUITING

Countries

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Australia Austria Denmark France Germany Sweden Switzerland United Kingdom

Central Contacts

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Maja Steinlin, Dr. med.

Role: CONTACT

+41 31 6329424

Kathrin Bochud, PhD

Role: CONTACT

+41316643472

Facility Contacts

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Russel Dale, Dr.

Role: primary

Russell Dale, Dr.

Role: primary

Mark MacKay, Prof. Dr.

Role: primary

Christian Lechner, OA Mag. MD

Role: primary

Biebl Ariane, PD MD

Role: primary

Rainer Seidl, Prof. Dr.

Role: primary

Karen Markussen Linnet, PhD

Role: primary

Malene Landbo Børresen, MD PhD

Role: primary

Beatrice Desnous, MD

Role: primary

Vincent Laugel, Pr, MD, PhD

Role: primary

Maryline Carneiro, Dr.

Role: primary

Laure Lacan, MD

Role: primary

Kumaran Deiva, Dr.

Role: primary

Manoëlle Kossorotoff, Dr.

Role: primary

Janbernd Kirschner, Pr., MD

Role: primary

Matthias Eckenweiler, MD

Role: backup

Lucia Gerstl, PD Dr.

Role: primary

Martin Olivieri, MD

Role: backup

Stefani Harmsen, MD

Role: primary

Annette Horn, MD

Role: backup

Timo Deba, MD

Role: primary

Roland Straeter, MD

Role: backup

Marc Nikolaus, MD

Role: primary

Bernhard Weschke, MD

Role: backup

Christian Menke, MD

Role: primary

Helena Marell Hessla, MD

Role: primary

Anna Gunnerbeck, MD

Role: backup

Stéphane Darteyre, MD

Role: primary

Barbara Goeggel Simonetti, PD Dr.

Role: primary

Reta Malär, MD

Role: primary

Susi Strozzi, MD

Role: backup

Nicole Faignart, MD

Role: primary

Claudia Poloni, MD

Role: backup

Alexandre Datta, PD Dr.

Role: primary

Gabriela Oesch Nemeth, MD

Role: primary

Joel Fluss, PD Dr.

Role: primary

Oliver Maier, Dr.

Role: primary

Annette Hackenberg, Dr.

Role: primary

Manali Chitre, MD

Role: primary

Jaspal Singh, Dr.

Role: primary

Dipak Ram, Dr.

Role: primary

Adrew Mallick, Dr.

Role: primary

References

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Steinlin M, O'callaghan F, Mackay MT. Planning interventional trials in childhood arterial ischaemic stroke using a Delphi consensus process. Dev Med Child Neurol. 2017 Jul;59(7):713-718. doi: 10.1111/dmcn.13393. Epub 2017 Jan 25.

Reference Type BACKGROUND
PMID: 28121022 (View on PubMed)

Fullerton HJ, Hills NK, Chen H, Dlamini N, Stence NV, Wintermark M; VIPS II Investigators. Changing Management of Focal Cerebral Arteriopathy of Childhood From 2010 to 2022. Stroke. 2025 Jun;56(6):1460-1468. doi: 10.1161/STROKEAHA.124.050550. Epub 2025 May 12.

Reference Type DERIVED
PMID: 40351190 (View on PubMed)

Related Links

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Other Identifiers

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2022-500631-36-00

Identifier Type: CTIS

Identifier Source: secondary_id

2021-005571-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2021-00453

Identifier Type: OTHER

Identifier Source: secondary_id

305395

Identifier Type: OTHER

Identifier Source: secondary_id

HREC/78937/RCHM-2022

Identifier Type: OTHER

Identifier Source: secondary_id

1473_PASTA

Identifier Type: -

Identifier Source: org_study_id

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