Corticosteroids for Pediatric Stroke

(FOCAS Trial)

Overseen By Maria A Kuchherzki, BA

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must be taking: Aspirin

Must not be taking: Corticosteroids

Disqualifiers: Prior stroke, Connective tissue disorder, Moyamoya, Autoimmune disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 month

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This comparative effectiveness trial (CET) in children with suspected focal cerebral arteriopathy (FCA) presenting with arterial ischemic stroke (AIS) or transient ischemic attack (TIA) will compare the use of early corticosteroid treatment (Arm A) versus delayed/no corticosteroid treatment (Arm B). Delayed corticosteroid treatment is given only for those demonstrating disease progression and is initiated as soon as the progression is detected (at any time after randomization). All participants will also receive standard of care therapy (aspirin and supportive care). Sites will randomize participants 1:1 to Arm A or B. Participants will be enrolled and randomized as soon as possible after their stroke/TIA up until 96 hours following the initial stroke/TIA event.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that all participants will receive standard care, including aspirin. If you are currently on corticosteroids, you may need to stop, as recent corticosteroid treatment is an exclusion criterion.

What data supports the effectiveness of the drug Methylprednisolone for pediatric stroke?

Research shows that corticosteroids like Methylprednisolone are used effectively in various inflammatory and autoimmune conditions in children, such as nephrotic syndrome and juvenile arthritis, suggesting potential benefits in reducing inflammation in pediatric stroke as well. ^{1 2 3 4 5}

Is it safe for children to use corticosteroids like Methylprednisolone?

Corticosteroids like Methylprednisolone have been used in various treatments, but there are reports of complications such as retinal toxicity when injected incorrectly and potential side effects when used for sports injuries. It's important to discuss potential risks with a healthcare provider. ^{4 6 7 8 9}

How is the drug Methylprednisolone unique for pediatric stroke treatment?

Methylprednisolone, a corticosteroid, is unique for pediatric stroke treatment because it is often used in high doses intravenously for its rapid anti-inflammatory effects, which may be beneficial in reducing brain swelling. This approach is different from standard treatments for stroke, which typically focus on restoring blood flow or preventing further clotting. ^{1 3 4 10 11}

Research Team

Heather J Fullerton, MD, MAS

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for children aged 1-18 who've had a stroke or TIA within the last 4 days, with imaging showing signs of focal cerebral arteriopathy. They must be able to return for follow-up MRI/MRA scans. Kids on recent steroids, pregnant/post-partum/nursing, with prior strokes or other specific risk factors are excluded.

Inclusion Criteria

You may need to have an additional MRI/MRA scan within 24 hours of joining the study.

Your initial imaging shows specific irregularities or damage in the blood vessels in your brain, or specific types of stroke in certain areas of your brain.

You can come back for a follow-up MRI/MRA scan within a month after the stroke.

Exclusion Criteria

My stroke or TIA is not caused by FCA, but intracranial dissection is considered.

I don't have conditions like lupus or recent drug use that could cause blood vessel problems.

I have heart conditions that could increase my risk of blood clots.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 days

1 visit (in-person)

Treatment

Participants receive corticosteroid treatment based on randomization to Arm A or Arm B

1 month

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Monthly visits (in-person or virtual)

Treatment Details

Interventions

• Methylprednisolone
• Prednisolone
• Prednisone

Trial Overview The study compares early versus delayed/no steroid treatment in kids after a stroke/TIA due to suspected focal cerebral arteriopathy. Participants will either receive immediate corticosteroids (methylprednisolone/prednisolone/prednisone) or delayed treatment if their condition worsens.

Participant Groups

Group I: Arm A Active Control 1 Intervention

Treat all children with suspected FCA with corticosteroids as soon as the diagnosis is made.

Group II: Arm B Active Control 1 Intervention

Treat only the subset of children that develop evidence of FCA disease progression.

Methylprednisolone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in European Union as Depo-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in Canada as Solu-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Findings from Research

In a study of 15 patients previously diagnosed with corticosteroid-induced arachnoiditis, only 3 exhibited the clinical symptoms of arachnoiditis, suggesting a low incidence of the condition among those affected.

The findings indicate that the severity of radiological changes did not correlate with the severity of symptoms, leading to the conclusion that methylprednisolone acetate (Depo-Medrol) should be avoided in procedures involving the thecal sac due to potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. Johnson, A., Ryan, MD., Roche, J.[2021]

Inadvertent injection of methylprednisolone acetate into the eye during vitrectomy can lead to severe retinal toxicity, resulting in significant vision loss and complications such as retinal necrosis and optic nerve damage.

This case highlights the critical need for careful identification of medications during eye surgeries to prevent serious adverse effects associated with incorrect injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. Yonekawa, Y., Sun, G., D'Amico, DJ., et al.[2014]

A survey of sports medicine physicians revealed that 47% prescribe methylprednisolone taper (Medrol Dosepak) for sports injuries, particularly in patients aged 40 and younger, with postinjury disease being the most common reason for its use.

Concerns about complications, especially the risk of osteonecrosis (reported in 8.5% of prescribers), and a lack of proven efficacy were significant reasons for the 52% of physicians who chose not to prescribe Medrol Dosepak.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of orthopaedic and sports medicine physicians regarding use of medrol dosepak for sports injuries. Langer, P., Fadale, P., Hulstyn, M., et al.[2018]

In a study of 901 patients with relapsing-remitting multiple sclerosis, methylprednisolone (MP) pulse therapy was administered with a mean frequency of 4 times, showing that the majority of patients received treatment multiple times, indicating its common use in managing acute exacerbations.

The study found that female patients were approximately 3.7 times more likely to seek MP pulse therapy compared to male patients, suggesting a gender difference in treatment-seeking behavior for MS management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary study related the incidence of methylprednisolone pulse therapy in patients visited multiple sclerosis clinic located at the isfahan kashani hospital. Tolou-Ghamari, Z., Shaygannejad, V., Ashtari, F.[2022]

References

1. India pubmed.ncbi.nlm.nih.gov

Pulse steroid therapy. [2022]

2. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Prednisolone oral solution plus inhaled procaterol for acute asthma in children: a double-blind randomized controlled trial. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Dexamethasone versus methylprednisolone for critical asthma: A single center, open-label, parallel-group clinical trial. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

[Comparative efficacy of oral deflazacort versus oral prednisolone in children with moderate acute asthma]. [2019]

5. Australia pubmed.ncbi.nlm.nih.gov

Beclomethasone dipropionate aerosol for asthmatic children requiring maintenance oral steroid therapy. [2013]

6. Australia pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. [2014]

8. United States pubmed.ncbi.nlm.nih.gov

Survey of orthopaedic and sports medicine physicians regarding use of medrol dosepak for sports injuries. [2018]

9. Iran pubmed.ncbi.nlm.nih.gov

Preliminary study related the incidence of methylprednisolone pulse therapy in patients visited multiple sclerosis clinic located at the isfahan kashani hospital. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Dexamethasone for Pediatric Critical Asthma: A Multicenter Descriptive Study. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

A Randomized Trial of Single-Dose Oral Dexamethasone Versus Multidose Prednisolone for Acute Exacerbations of Asthma in Children Who Attend the Emergency Department. [2018]