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Studies

Interventional Not yet recruiting Phase 3

NCT07281027 on ClinicalTrials.gov

COMparison Between Anakinra and Tocilizumab in NORSE - "COMBAT-NORSE"

Official title: Comparing the Effects of Anakinra and Tocilizumab on Outcomes in Patients With New-Onset Refractory Status Epilepticus

  • Sponsor: Yale University
  • Collaborators: Patient-Centered Outcomes Research Institute
  • Enrollment: 438 (Estimated)
  • Study start: 2026-12-01 (Estimated)
  • Primary completion: 2030-03-31 (Estimated)
  • Study completion: 2030-09-30 (Estimated)
  • Allocation: Randomized
  • InterventionModel: Parallel
  • Masking: Single (Outcomes Assessor)
  • PrimaryPurpose: Treatment

Brief Summary

The goal of this clinical trial is to find out whether two existing medications-anakinra and tocilizumab-can effectively treat a rare and life-threatening brain condition called NORSE (New-Onset Refractory Status Epilepticus). NORSE causes continuous seizures in previously healthy children and adults and does not respond to standard treatments. It often leads to long-term disability or death.

Doctors currently use anakinra and tocilizumab as second-line treatments when first-line therapies fail, but there is no clear evidence showing which drug works better or when it should be given. This study aims to answer those questions.

The study will enroll patients across 33 hospitals in the United States, Canada, Europe, and Asia.

It includes two groups:

1. Randomized Cohort Patients will be randomly assigned to receive either anakinra or tocilizumab within the first 7 days of their illness. Only patients whose doctors were already planning to use one of these medications as part of standard care will be eligible for randomization. Researchers will monitor their recovery and compare outcomes between the two treatments.
2. Observational Cohort Patients who cannot be randomized-usually because they were diagnosed too late-will still be followed to study how the timing of treatment affects recovery.

Participants will:

* Receive one of the two medications (depending on their group assignment).
* Take part in follow-up assessments over the course of one year, including medical evaluations and surveys. Some participants may be followed annually beyond one year.
* Optionally participate in a 60-minute interview to share their or their caregiver's experience with NORSE.

Conditions

  • New Onset Refractory Status Epilepticus
  • New-Onset Refractory Status Epilepticus
  • Febrile Infection-Related Epilepsy Syndrome (FIRES)

Intervention / Treatment

  • Drug: Anakinra
  • Drug: Tocilizumab
  • Other: Standard medical treatment

Primary Outcome Measures

  • Glasgow Outcome Scale - Extended (GOS-E) (12 months)
    The Glasgow Outcome Scale - Extended (GOS-E) is an 8-point scale used to measure global functional outcome. Participants are scored into one of the 8 categories: 1. Death, 2. Vegetative State, 3. Lower Severe Disability, 4. Upper Severe Disability, 5. Lower Moderate Disability, 6. Upper Moderate Disability, 7. Lower Good Recovery, 8. Upper Good Recovery.

Countries

Canada, France, Italy, South Korea, Sweden, United Kingdom, United States

Locations and Investigators

  • Barrow Institute, Phoenix, United States
    • Susan Herman
  • Children's Hospital Colorado, Aurora, United States
    • Krista Eschbach
  • Yale New Haven Hospital, New Haven, United States
    • Lawrence Hirsch
  • Children's National (DC), Washington D.C., United States
    • Elizabeth Wells
  • University of Florida, Gainesville, United States
    • Carolina Maciel
  • University of Chicago, Chicago, United States
    • Hiba Haider
  • Northwestern University, Evanston, United States
    • Stephen vanHaerents
  • Mass General (MGH), Boston, United States
    • Sahar Zafar
  • Beth Israel Deaconess, Boston, United States
    • Brandon Westover
  • Boston Children's Hospital, Boston, United States
    • Coral Stredny
  • Mayo Clinic, Rochester, United States
    • Kelsey Smith
  • University of Nebraska, Lincoln, United States
    • Olga Taraschenko
  • New York University, New York, United States
    • Claude Steriade
  • Columbia University, New York, United States
    • Jan Claassen
  • Mount Sinai (NY), New York, United States
    • Ji Yeoun Yoo
  • University of Cincinnati, Cincinnati, United States
    • Brandon Foreman
  • Cleveland Clinic, Cleveland, United States
    • Vineet Punia
  • Oregon Health and Science University, Portland, United States
    • Marissa Kellogg
  • Children's Hospital Philadelphia (CHOP), Philadelphia, United States
    • Danielle Decampo
  • University of Pennsylvania, Philadelphia, United States
    • Catherine Kulick
  • UT Southwestern Medical Center, Dallas, United States
    • Rana Said
  • Baylor/Texas Children's, Houston, United States
    • Yichen Lai
  • Seattle Children's Hospital, Seattle, United States
    • Mark Wainwright
  • University of Wisconsin, Madison, United States
    • Aaron Struck
  • Medical College of Wisconsin, Milwaukee, United States
    • Raquel Farias-Moeller
  • Western University, London, Canada
    • Teneille Gofton
  • Hospital for Sick Children, Toronto, Canada
    • Cecil Hahn
  • Salpêtrière, Paris, France
    • Vincent Navarro
  • University of Modena, Modena, Italy
    • Stefano Meletti
  • Seoul National University Hospital, Seoul, South Korea
    • Soon-Tae Lee
  • Karolinska Institute, Stockholm, Sweden
    • Ronny Wickstrom
  • Great Ormond Street Hospital, London, United Kingdom
    • Marios Kaliakatsos
  • King's College, London, United Kingdom
    • Laura Mantoan

Study Officials