Ignite Creation Date:
2025-12-25 @ 5:09 AM
Ignite Modification Date:
2025-12-26 @ 4:13 AM
Study NCT ID:
NCT07281027
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-15
First Post:
2025-11-21
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
COMparison Between Anakinra and Tocilizumab in NORSE - "COMBAT-NORSE"
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D013226', 'term': 'Status Epilepticus'}], 'ancestors': [{'id': 'D012640', 'term': 'Seizures'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D053590', 'term': 'Interleukin 1 Receptor Antagonist Protein'}, {'id': 'C502936', 'term': 'tocilizumab'}], 'ancestors': [{'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 438}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-03-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2030-09-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-03', 'studyFirstSubmitDate': '2025-11-21', 'studyFirstSubmitQcDate': '2025-12-03', 'lastUpdatePostDateStruct': {'date': '2025-12-15', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-12-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2030-03-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Glasgow Outcome Scale - Extended (GOS-E)', 'timeFrame': '12 months', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Time to resolution of status epilepticus (SE)', 'timeFrame': '24 hours off anesthetic drips', 'description': 'Time (days) until discontinuation of anesthetic drips for 24h for the treatment of SE with no return of SE on EEG'}, {'measure': 'Hospital length of stay', 'timeFrame': '12 months', 'description': 'Mean number of days during hospitalization from admission to discharge'}, {'measure': 'Mortality', 'timeFrame': 'up to 12 months', 'description': 'Mortality, number of participants'}, {'measure': 'Number of serious adverse events attributed to anakinra or tocilizumab', 'timeFrame': 'From hospitalization to 1 month after stopping treatment, up to 12 months', 'description': 'Number of serious adverse events attributed to anakinra or tocilizumab'}, {'measure': 'Number of participants Post-NORSE epilepsy', 'timeFrame': '12 months', 'description': 'Number of participants with any unprovoked seizures after hospital discharge'}, {'measure': 'Number of participants with Treatment success', 'timeFrame': '12 months', 'description': 'Combined measure of lack of need for another immunomodulator after the study drug was begun, plus good outcome at 1 year (GOS-E of 5-8) (Yes/No)'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['refractory status epilepticus', 'NORSE', 'FIRES', 'anakinra', 'tocilizumab'], 'conditions': ['New Onset Refractory Status Epilepticus', 'New-Onset Refractory Status Epilepticus', 'Febrile Infection-Related Epilepsy Syndrome (FIRES)']}, 'descriptionModule': {'briefSummary': "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.\n\nDoctors 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.\n\nThe study will enroll patients across 33 hospitals in the United States, Canada, Europe, and Asia.\n\nIt includes two groups:\n\n1. 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.\n2. 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.\n\nParticipants will:\n\n* Receive one of the two medications (depending on their group assignment).\n* 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.\n* Optionally participate in a 60-minute interview to share their or their caregiver's experience with NORSE."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '2 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age 2 and older.\n* In their usual state of health prior to their onset of SE.\n* Presenting with NORSE as defined in the consensus criteria:\n\n 1. Refractory SE (failed 2 appropriately used anti-seizure medications) in a patient without active epilepsy or other pre-existing relevant neurological disorder and without an acute or active structural, toxic, or metabolic cause found in the first 72 hours.\n 2. Includes patients with any RSE, not just super-refractory SE.\n 3. Includes patients who ultimately are discovered to have a known etiology (infectious, autoimmune, genetic, etc.), as well as those who remain cryptogenic.\n\n * Additional Inclusion Criteria for the Randomized Arm:\n* Anakinra and/or tocilizumab are being planned or considered as part of standard clinical care.\n* The onset of SE was in the prior 7 days at the time of enrollment.\n\nExclusion Criteria:\n\n* Any acute or active systemic medical illness such as metastatic cancer, renal failure, hepatic failure, poorly controlled diabetes, etc., in the opinion of the investigators. If this is unclear, the study PI Dr. Hirsch will determine if this criterion is met.\n\nAdditional Exclusion Criteria for the Randomized Control Cohort:\n\n* Contraindication to either anakinra or tocilizumab as listed in the prescribing information:\n\n 1. Known hypersensitivity to E. Coli-derived proteins, anakinra, tocilizumab, or any component of the products\n 2. Active serious infection at the time of initiation\n 3. Concomitant use of TNF blocking agents; absolute neutrophil count \\< 2000; platelet count \\< 100,000 per mm³; or ALT or AST \\> 1.5 X the upper limit of normal\n 4. Elevated risk of GI perforation.'}, 'identificationModule': {'nctId': 'NCT07281027', 'acronym': 'COMBAT-NORSE', 'briefTitle': 'COMparison Between Anakinra and Tocilizumab in NORSE - "COMBAT-NORSE"', 'organization': {'class': 'OTHER', 'fullName': 'Yale University'}, 'officialTitle': 'Comparing the Effects of Anakinra and Tocilizumab on Outcomes in Patients With New-Onset Refractory Status Epilepticus', 'orgStudyIdInfo': {'id': '2000041289'}, 'secondaryIdInfos': [{'id': 'RD-2024C2-39648', 'type': 'OTHER_GRANT', 'domain': 'PCORI'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Randomized Controlled Trial (RCT) Cohort', 'description': 'A randomized controlled cohort (RCT) of anakinra vs. tocilizumab (targeted immunotherapies) started up to and including 7 days after the onset of status epilepticus (SE)', 'interventionNames': ['Drug: Anakinra', 'Drug: Tocilizumab']}, {'type': 'OTHER', 'label': 'Observational Cohort', 'description': 'An observational cohort enrolling patients with acute cryptogenic NORSE who cannot be randomized or who are identified too late to be randomized by the end of day 7 .', 'interventionNames': ['Other: Standard medical treatment']}], 'interventions': [{'name': 'Anakinra', 'type': 'DRUG', 'description': 'SOC will be followed , Suggested Dose:\n\n10 mg/kg/day IV, divided into 4 daily doses (q6h) Maximum dose: 400 mg/day', 'armGroupLabels': ['Randomized Controlled Trial (RCT) Cohort']}, {'name': 'Tocilizumab', 'type': 'DRUG', 'description': 'SOC will be followed,\n\nSuggested Dose:\n\nIf \\<30 kg: 12 mg/kg IV once every 2 weeks If ≥30 kg: 8 mg/kg IV once every 2 weeks Maximum dose: 800 mg per dose', 'armGroupLabels': ['Randomized Controlled Trial (RCT) Cohort']}, {'name': 'Standard medical treatment', 'type': 'OTHER', 'description': 'For patients who could not be randomized by day 7, standard clinical care will be followed and patients will be followed prospectively and observationally.', 'armGroupLabels': ['Observational Cohort']}]}, 'contactsLocationsModule': {'locations': [{'zip': '85013', 'city': 'Phoenix', 'state': 'Arizona', 'country': 'United States', 'contacts': [{'name': 'Susan Herman', 'role': 'CONTACT', 'email': 'susan.herman@commonspirit.org'}], 'facility': 'Barrow Institute', 'geoPoint': {'lat': 33.44838, 'lon': -112.07404}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'contacts': [{'name': 'Krista Eschbach', 'role': 'CONTACT', 'email': 'krista.eschbach@childrenscolorado.org'}], 'facility': "Children's Hospital Colorado", 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '06520', 'city': 'New Haven', 'state': 'Connecticut', 'country': 'United States', 'contacts': [{'name': 'Lawrence Hirsch', 'role': 'CONTACT', 'email': 'lawrence.hirsch@yale.edu'}], 'facility': 'Yale New Haven Hospital', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}, {'zip': '20010', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'contacts': [{'name': 'Elizabeth Wells', 'role': 'CONTACT', 'email': 'ewells@childrensnational.org'}], 'facility': "Children's National (DC)", 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '32611', 'city': 'Gainesville', 'state': 'Florida', 'country': 'United States', 'contacts': [{'name': 'Carolina Maciel', 'role': 'CONTACT', 'email': 'carolina.maciel@neurology.ufl.edu'}], 'facility': 'University of Florida', 'geoPoint': {'lat': 29.65163, 'lon': -82.32483}}, {'zip': '60637', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'contacts': [{'name': 'Hiba Haider', 'role': 'CONTACT', 'email': 'hibahaider@uchicago.edu'}], 'facility': 'University of Chicago', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '60208', 'city': 'Evanston', 'state': 'Illinois', 'country': 'United States', 'contacts': [{'name': 'Stephen vanHaerents', 'role': 'CONTACT', 'email': 'svanhaer@nm.org'}], 'facility': 'Northwestern University', 'geoPoint': {'lat': 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'facility': 'Seoul National University Hospital', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'city': 'Stockholm', 'country': 'Sweden', 'contacts': [{'name': 'Ronny Wickstrom', 'role': 'CONTACT', 'email': 'ronny.wickstrom@ki.se'}], 'facility': 'Karolinska Institute', 'geoPoint': {'lat': 59.32938, 'lon': 18.06871}}, {'city': 'London', 'country': 'United Kingdom', 'contacts': [{'name': 'Marios Kaliakatsos', 'role': 'CONTACT', 'email': 'marios.kaliakatsos@gosh.nhs.uk'}], 'facility': 'Great Ormond Street Hospital', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'city': 'London', 'country': 'United Kingdom', 'contacts': [{'name': 'Laura Mantoan', 'role': 'CONTACT', 'email': 'laura.mantoan@kcl.ac.uk'}], 'facility': "King's College", 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'centralContacts': [{'name': 'Camalene Chrysostoum', 'role': 'CONTACT', 'email': 'camalene.chrysostoum@yale.edu', 'phone': '2037375851'}, {'name': 'Tara McPartland', 'role': 'CONTACT', 'email': 'tara.mcpartland@yale.edu', 'phone': '2037375851'}], 'overallOfficials': [{'name': 'Lawrence Hirsch, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Yale University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Making the Full Data Package available to enable other researchers (including PCORI) to use it to re-analyze the data or for independent (i.e., novel) research analyses.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Yale University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Patient-Centered Outcomes Research Institute', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Neurology', 'investigatorFullName': 'Lawrence Hirsch', 'investigatorAffiliation': 'Yale University'}}}}