<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03249844</url>
  </required_header>
  <id_info>
    <org_study_id>1608184</org_study_id>
    <secondary_id>2017-002247-15</secondary_id>
    <nct_id>NCT03249844</nct_id>
  </id_info>
  <brief_title>Paediatric Arteriopathy Steroid Aspirin Project</brief_title>
  <acronym>PASTA</acronym>
  <official_title>High Dose Steroids in Children With Stroke and Unilateral Focal Arteriopathy: Paediatric Arteriopathy Steroid Aspirin (PASTA) Project. A Multicentre Randomized Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Saint Etienne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Saint Etienne</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Arterial ischemic stroke (AIS) is a devastating condition, affecting 1.6-5/100,000&#xD;
      children/year. Although their outcome is different, children with stroke do not recover&#xD;
      better than adults, with at least 2/3 suffering long term sequels such as developmental&#xD;
      (motor, global intellectual, language...) and behavioral disabilities, epilepsy, and low&#xD;
      adaptative and academic skills...&#xD;
&#xD;
      Stenotic cerebral arteriopathy is identified as AIS etiology in 60-80% of previously healthy&#xD;
      children and the course of this arteriopathy is the strongest predictor of recurrent events.&#xD;
      30-40% of these children have a focal unilateral cerebral arteriopathy (FCA). Childhood FCA&#xD;
      is suspected to be an inflammatory vessel wall pathology triggered by varicella and other&#xD;
      (viral) infections. As recurrences occur for the great majority in the first 6 months after&#xD;
      the index event, aspirin 5 mg/kg/day is recommended for at least 18 months to 2 years.&#xD;
&#xD;
      As there is a rational for using immunomodulatory drugs at the acute stage of FCA,&#xD;
      immunotherapies are currently used by neuropaediatricians in AIS, mainly as steroids for&#xD;
      children with stenosing arteriopathies. However, due to weak evidences, the literature cannot&#xD;
      either encourage or discourage this practice.&#xD;
&#xD;
      The long term course of children with FCA is only approach to date by retrospective studies&#xD;
      and controversies about outcome remain (for example, the recurrence risk on antithrombotic&#xD;
      treatment varies notably from quasi zero to 25%). And finally, it is shown in childhood&#xD;
      stroke, as well as in the global field of longstanding impairment, that parental and medical&#xD;
      points of view do not match consistently. Longitudinal studies are needed to deserve this&#xD;
      familial approach.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    discontinuation of the trial&#xD;
  </why_stopped>
  <start_date type="Anticipated">September 1, 2022</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2027</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The outcome assessor don't know patient treatment</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Time to recovery up to 12 months</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Evaluate of time to recovery up to 12 months by score paediatric Recurrence and Recovery Questionnaire (RRQ )</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement of functional outcome by face-to-face visits</measure>
    <time_frame>Months:1,6,12, 24 and 36</time_frame>
    <description>Evaluate of Improvement of functional outcome by face-to-face visits by score Paediatric Stroke Outcome Measure (PSOM), modified Rankin Scale (mRS) and Vineland Adaptive Behaviour Scale (VABS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arteriopathic course along time</measure>
    <time_frame>Months: 1, 6, 24</time_frame>
    <description>Evaluate of Arteriopathic course along time by comparison between magnetic resonance (MR) arteriography and initial imaging.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence of stroke, epilepsy, neurological and developmental sequels, and academic achievement</measure>
    <time_frame>Months: 1, 3, 6,12, 24 and 36</time_frame>
    <description>Evaluate recurrence of stroke, epilepsy, neurological and developmental sequels, and academic achievement at 6, 12, 24 and 36 months. Neurological outcome will be assessed by standard clinical examination: motricity, sensibility, coordination, oculomotricity and visual field, cranial nerves…</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Outcome by age group</measure>
    <time_frame>Months 72</time_frame>
    <description>Evaluate outcome by age group. All endpoints will be stratified for the whole cohort by the following age group: 0.5-3 years; 3-6 years; 6-10 years and ≥10 years. This will be done in a centrally-manner at Clinical Trials Unit (CTU) Bern.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Familial impact</measure>
    <time_frame>Months 72</time_frame>
    <description>Evaluate of familial impact by Alberta Perinatal Stroke Parental Outcome Measure (APSOM) and indepth interview through semi-structured interviews. The objective is to report the lived experience of parents whose child was included in the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of serious adverse events</measure>
    <time_frame>Months 72</time_frame>
    <description>Analysis of number of serious adverse events and their cause, consequence.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Arterial Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children will be treated by methylprednisolone + prednisolone and standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Children will be treated by standard of care alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylprednisolone + prednisolone</intervention_name>
    <description>The experimental intervention consists of 5 consecutive days Methylprednisolone at a daily single intravenous dose of 20 mg/kg body-weight (max 1 g/day) followed by a 4-week course of tapering Prednisolone given at a daily single oral dose in the morning:&#xD;
week 1 and 2, oral Prednisolone 1 mg/kg/day (max 40 mg/day), ,&#xD;
week 3 and 4, oral Prednisolone 0,5 mg/kg/day (max 20 mg/day),</description>
    <arm_group_label>experimental group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -- Aged 6 months to &lt;15 years&#xD;
&#xD;
          -  AIS ≤ 48 hours&#xD;
&#xD;
               -  Newly acquired focal neurological deficit with confirmation by magnetic resonance&#xD;
                  imaging (MRI) of ischaemic lesion in an arterial territory corresponding with the&#xD;
                  clinical features (definition of Arterial ischemic stroke).&#xD;
&#xD;
               -  Magnetic resonance arteriography showing unilateral proximal stenosis or&#xD;
                  irregularities of the corresponding carotid trifurcation (i.e. terminal carotid&#xD;
                  and/or M1-M2 and/or A1 segments) or of the posterior circulation (P1-P2&#xD;
                  segments).&#xD;
&#xD;
               -  No evidence of an underlying systemic disorder (e.g. lupus erythematodes)&#xD;
                  explaining the features.&#xD;
&#xD;
               -  Informed and signed consent of parents or legal guardians.&#xD;
&#xD;
          -  French Social Security (Sécurité sociale; i.e. national health coverage) affiliation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children with secondary central nervous system angiitis due to infections (meningitis,&#xD;
             endocarditis, borreliosis), rheumatic or other systemic inflammatory diseases (e.g.&#xD;
             lupus erythematodes). These children are already under immune suppression or need&#xD;
             other co-medications regarding their underlying disease.&#xD;
&#xD;
          -  Children with known syndromal and/or genetic vasculopathies such as phaces syndrome,&#xD;
             Neurofibromatosis type 1, trisomy 21.&#xD;
&#xD;
          -  Children with moyamoya or sickle cell disease.&#xD;
&#xD;
          -  Children with a progressive large to medium vessel childhood primary angiitis of the&#xD;
             central nervous system with two out of the following three criteria : Children with&#xD;
             progressive neurocognitive dysfunction; Children with bilateral lesions/vessel&#xD;
             involvement; Children with distal arterial stenosis (beyond the M2, A1 or P2 segment).&#xD;
&#xD;
             - Children already on steroid treatment at disease onset or with a contraindication to&#xD;
             receive steroid treatment (e.g. congenital or acquired immunodeficiency).&#xD;
&#xD;
          -  Children with delayed diagnosis ≥3 days as treatment start is not allowed to be more&#xD;
             ≥5 day-delayed.&#xD;
&#xD;
          -  Contraindications to steroids (see also summary of product characteristics in chapter&#xD;
             1.1) and notably: Not-manageable infectious, hydro-electrolytic or metabolic (e.g.&#xD;
             diabetes mellitus) disorders, or elevated blood pressure, Serious behavioral&#xD;
             disorders, Current vaccination with live or attenuated live strains,&#xD;
             Allergy/sensibility to any ingredient, Association with some medications such as&#xD;
             antiarrhythmic drugs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stéphane CHABRIER, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU SAINT-ETIENNE</affiliation>
  </overall_official>
  <removed_countries>
    <country>France</country>
  </removed_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>October 17, 2022</last_update_submitted>
  <last_update_submitted_qc>October 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>arterial ischemic stroke</keyword>
  <keyword>children</keyword>
  <keyword>steroids</keyword>
  <keyword>aspirin</keyword>
  <keyword>Methylprednisolone</keyword>
  <keyword>Prednisolone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
    <mesh_term>Methylprednisolone Hemisuccinate</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Prednisolone acetate</mesh_term>
    <mesh_term>Prednisolone hemisuccinate</mesh_term>
    <mesh_term>Prednisolone phosphate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03249844
org study id: 1608184
secondary id: 2017-002247-15
nct id: NCT03249844
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Arterial ischemic stroke (AIS) is a devastating condition, affecting 1.6-5/100,000
      children/year. Although their outcome is different, children with stroke do not recover
      better than adults, with at least 2/3 suffering long term sequels such as developmental
      (motor, global intellectual, language...) and behavioral disabilities, epilepsy, and low
      adaptative and academic skills...

      Stenotic cerebral arteriopathy is identified as AIS etiology in 60-80% of previously healthy
      children and the course of this arteriopathy is the strongest predictor of recurrent events.
      30-40% of these children have a focal unilateral cerebral arteriopathy (FCA). Childhood FCA
      is suspected to be an inflammatory vessel wall pathology triggered by varicella and other
      (viral) infections. As recurrences occur for the great majority in the first 6 months after
      the index event, aspirin 5 mg/kg/day is recommended for at least 18 months to 2 years.

      As there is a rational for using immunomodulatory drugs at the acute stage of FCA,
      immunotherapies are currently used by neuropaediatricians in AIS, mainly as steroids for
      children with stenosing arteriopathies. However, due to weak evidences, the literature cannot
      either encourage or discourage this practice.

      The long term course of children with FCA is only approach to date by retrospective studies
      and controversies about outcome remain (for example, the recurrence risk on antithrombotic
      treatment varies notably from quasi zero to 25%). And finally, it is shown in childhood
      stroke, as well as in the global field of longstanding impairment, that parental and medical
      points of view do not match consistently. Longitudinal studies are needed to deserve this
      familial approach.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The outcome assessor don't know patient treatment
measure: Time to recovery up to 12 months
time frame: Up to 12 months
description: Evaluate of time to recovery up to 12 months by score paediatric Recurrence and Recovery Questionnaire (RRQ )
measure: Improvement of functional outcome by face-to-face visits
time frame: Months:1,6,12, 24 and 36
description: Evaluate of Improvement of functional outcome by face-to-face visits by score Paediatric Stroke Outcome Measure (PSOM), modified Rankin Scale (mRS) and Vineland Adaptive Behaviour Scale (VABS).
measure: Arteriopathic course along time
time frame: Months: 1, 6, 24
description: Evaluate of Arteriopathic course along time by comparison between magnetic resonance (MR) arteriography and initial imaging.
measure: Recurrence of stroke, epilepsy, neurological and developmental sequels, and academic achievement
time frame: Months: 1, 3, 6,12, 24 and 36
description: Evaluate recurrence of stroke, epilepsy, neurological and developmental sequels, and academic achievement at 6, 12, 24 and 36 months. Neurological outcome will be assessed by standard clinical examination: motricity, sensibility, coordination, oculomotricity and visual field, cranial nerves…
measure: Outcome by age group
time frame: Months 72
description: Evaluate outcome by age group. All endpoints will be stratified for the whole cohort by the following age group: 0.5-3 years; 3-6 years; 6-10 years and ≥10 years. This will be done in a centrally-manner at Clinical Trials Unit (CTU) Bern.
measure: Familial impact
time frame: Months 72
description: Evaluate of familial impact by Alberta Perinatal Stroke Parental Outcome Measure (APSOM) and indepth interview through semi-structured interviews. The objective is to report the lived experience of parents whose child was included in the study.
measure: Number of serious adverse events
time frame: Months 72
description: Analysis of number of serious adverse events and their cause, consequence.
arm group label: experimental group
arm group type: Experimental
description: Children will be treated by methylprednisolone + prednisolone and standard of care
arm group label: control group
arm group type: No Intervention
description: Children will be treated by standard of care alone
intervention type: Drug
intervention name: Methylprednisolone + prednisolone
description: The experimental intervention consists of 5 consecutive days Methylprednisolone at a daily single intravenous dose of 20 mg/kg body-weight (max 1 g/day) followed by a 4-week course of tapering Prednisolone given at a daily single oral dose in the morning:
week 1 and 2, oral Prednisolone 1 mg/kg/day (max 40 mg/day), ,
week 3 and 4, oral Prednisolone 0,5 mg/kg/day (max 20 mg/day),
arm group label: experimental group
criteria: 
gender: All
minimum age: 6 Months
maximum age: 15 Years
healthy volunteers: No
last name: Stéphane CHABRIER, MD
role: Principal Investigator
affiliation: CHU SAINT-ETIENNE
country: France
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Methylprednisolone
mesh term: Methylprednisolone Acetate
mesh term: Methylprednisolone Hemisuccinate
mesh term: Prednisolone
mesh term: Prednisolone acetate
mesh term: Prednisolone hemisuccinate
mesh term: Prednisolone phosphate
sharing ipd: No